The Efficacy and Safety of Traditional Chinese Medicine Qufenghuoxue Formula on Peripheral Neuropathy Induced by Paclitaxel in Advanced Lung Cancer：A Randomized Clinical Trial

The Efficacy and Safety of Traditional Chinese Medicine Qufenghuoxue Formula on Peripheral Neuropathy Induced by Paclitaxel in Advanced Lung Cancer：A Randomized Clinical Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Efficacy and Safety of Traditional Chinese Medicine Qufenghuoxue Formula on Peripheral Neuropathy Induced by Paclitaxel in Advanced Lung Cancer：A Randomized Clinical Trial Yijun Song, Zhidan Hua, Mengting Sun, Nuo Xu, Xinyuan Lu, Dawei Yang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6802916/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Dec, 2025 Read the published version in Supportive Care in Cancer → Version 1 posted 10 You are reading this latest preprint version Abstract Purpose To assess the benefits of hands and feet immersion with traditional Chinese medicine (TCM) Qufenghuoxue formula on chemotherapy-induced peripheral neuropathy (CIPN) in advanced lung cancer patients receiving paclitaxel. Methods In this prospective trial, 227 patients with CIPN grading 2–3 randomly received TCM therapy, oral vitamin B1 or warm water immersion during paclitaxel chemotherapy. Assessment measures such as Neuropathy Pain Scale (NPS), and the potential of completing recommended paclitaxel dosing were used to evaluate the efficacy. Results The incidence of sensory peripheral neuropathy and motor peripheral neuropathy with NCI-CTCAE grading 2–3 dropped to 83.3% and 73.6% in TCM group, significantly lower than vitamin B1 and warm water groups (P < 0.001). TCM therapy improved FACT/GOG-Ntx (11.5 vs 20.4 vs 22.4), NPS (16.8 vs 27.7 vs 29.2) and Quality of Life scales (42.6 vs 36.0 vs 33.6) (all P < 0.001). Compared to vitamin B1 and warm water groups, more patients in TCM group experienced CIPN relief (48.6% vs 12.0% vs 7.5%, P < 0.001) with decreased mean time to CIPN relief. TCM group also had greater potential of completing recommended dose level of paclitaxel (83.8% vs 74.6% vs 59.7%, P = 0.0034). With warm water as a reference, the multivariate hazard ratio of paclitaxel dose reductions/cessation as a result of CIPN was 0.34 for TCM and 0.56 for vitamin B1. Conclusion Qufenghuoxue formula was a feasible strategy in relieving CIPN-related symptoms, reducing CIPN severity grading, and improving the potential of completing recommended paclitaxel dosing in advanced lung cancer patients. Trial Registration Chinese Clinical Trial Registry No. ChiCTR2300069949. Registered 30 March 2023, URL www.chictr.org/cn/. Paclitaxel chemotherapy-induced peripheral neuropathy advanced lung cancer traditional Chinese medicine recommended chemotherapy dose randomized clinical trial Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Paclitaxel (PTX) is considered to be one of the main chemotherapy for advanced lung cancer 1 – 3 . However, chemotherapy-induced peripheral neuropathy (CIPN), including sensory peripheral neuropathy (SPN) and motor peripheral neuropathy (MPN), is one of the most dose-limiting side effects of PTX administration 4 . Up to 90% of cancer patients develop CIPN during or after chemotherapy with 30% continuing to suffer permanently 5 , 6 . These side effects frequently lead to chemotherapy dose reduction or cessation, worsening treatment outcomes and quality of life⁷. Currently, there are no treatment strategies that effectively prevent or attenuate CIPN-related symptoms, leaving disease management largely symptomatic and palliative. Patients may develop acute neurological symptoms within hours or days of chemotherapy, persisting for months⁷. CIPN significantly impacts quality of life and survival, necessitating effective management to alleviate symptoms and maintain optimal paclitaxel dosing. Current treatments, including narcotics, antidepressants, anticonvulsants, vitamins, and acupuncture, provide limited relief⁸. While vitamin B, cryotherapy, and gradient pressure show potential in reducing CIPN risk, conclusive evidence is still lacking⁹⁻¹¹. Notably, moderate to severe CIPN continues to plague patients and medical fraternity, driving the need for innovative therapies¹². The pathophysiology of CIPN involves microtubule disruption, neuroinflammation, oxidative stress, and homeostasis imbalance 7 , 8 . In Traditional Chinese Medicine (TCM) theory, CIPN is ascribed to "blockage syndrome" (“Bi Zheng”) 9 . Hands and feet immersion of TCM may alleviate neuropathic symptoms by stimulating meridian points and promoting transdermal drug absorption 10 . For example, Qufenghuoxue formula may enhance neurotransmitter activity and microcirculation to address "blockage syndrome" via immersion. TCM is widely accessible, well-tolerated, and rarely causes severe side effects, aligning with its principle of external treatment for internal disorders 9 , 11 . This study compares the efficacy and safety of Qufenghuoxue formula, vitamin B1, and warm water in treating CIPN among advanced lung cancer patients. Materials and methods Patients and study design The investigator-initiated, open-label randomized study evaluated the efficacy and safety of hands and feet immersion with Qufenghuoxue formula for CIPN among advanced lung cancer patients. A total of 227 patients developing CIPN after PTX-based chemotherapy were enrolled. Both PTX (nanoparticle albumin-bound paclitaxel (nab-PTX) 260 mg/m 2 or docetaxel 75 mg/m 2 ) and platinum agents were given every three weeks. The inclusion criteria include: (1) Advanced lung cancer (pathologically confirmed at Zhongshan Hospital); (2) PTX-induced CIPN (National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading 2–3); (3) Willing to attend visits and complete questionnaires every three weeks; (4) Age > 18 years old, life expectancy ≥ 6 months; (5) Eastern Cooperative Oncology Group (ECOG) performance score (PS) 0–2. Patients who had skin damage on hands and feet or failed to complete the questionnaires were excluded from the study. 227 advanced lung cancer patients with CIPN were randomized into three groups (Fig. 1 ): (1) TCM group: Qufenghuoxue formula (nine herbs, see Supplementary table 1 ) for hands and feet immersion (30 minutes, twice daily); (2) Vitamin B1 group: Oral vitamin B1 (10 mg, three times daily); (3) Warm water group: Hands and feet immersion in 40℃ water (30 minutes, twice daily). The quality of herbs complied with the 2020 Chinese pharmacopoeia, and safety tests for heavy metals, microbial contamination and residual pesticides met national standards 12 . PTX dose reductions or discontinuation were considered for severe adverse events, including CIPN; patients were censored if dosing changed for non-neuropathy reasons. Demographic and clinical data were collected from May 2023 to August 2024 at Zhongshan Hospital, Fudan University. The study (B2021-257R, ChiCTR2300069949) complied with the Declaration of Helsinki and was approved by the hospital’s ethics committee. All participants provided informed consent. Peripheral Neuropathy Assessments Neuropathy assessments were conducted at baseline and every three weeks before chemotherapy. The severity of SPN and MPN was evaluated by NCI-CTCAE version 5.0 (Grade 1–5) (Supplementary table 2). CIPN relief was defined as a reduction in SPN or MPN severity grading, with relief time recorded from study entry to the first occurrence of CIPN relief. Subjective neuropathy symptoms were evaluated using: (1) Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-NTx) (score 0–44; higher = worse neuropathic symptoms): Ntx subscale contains eleven neurotoxicity items assessing SPN, MPN, hearing neuropathy, and neuropathic dysfunction associated with neurotoxicity symptoms 10 , 13 (Supplementary Table 3). (2) Neuropathy Pain Scale (NPS) (score 0–100; higher = worse neuropathic pain): NPS utilizes self-report visual analogue scales to quantify neuropathic pain intensity and distinguish it from non-neuropathic pain 14 , 15 (Supplementary Table 4). Quality of Life (QoL) was assessed through a 12-item scale (score 0–60; higher = better QoL), covering appetite, mental state, pain, daily activities, and side effects of treatment 16 (Supplementary Table 5). Data Collection Demographic and clinical data were collected from medical recording system, including age, gender, weight, height, ECOG PS, histology, tumor stage, tumor status, treatment lines, chemotherapy modalities, and cumulative PTX dose. Tumor status was assessed periodically via tumor markers and CT scans. Relative dose intensity of PTX was calculated as (cumulative administered dose / planned dose) × 100% 17 . Patients self-reported FACT/GOG-Ntx, NPS, and QoL scales, with physicians assisting older or illiterate patients. During follow-ups, physicians recorded PTX doses, dose adjustments, CIPN grade, adverse effects, and tumor responses assessed by Response Evaluation Criteria in Solid Tumors v1.1. Pulmonologists independently adjusted chemotherapy based on toxicity. All dose modifications, delays, or cessations were documented. Statistical Analysis The primary endpoint was the efficacy and safety of Qufenghuoxue formula versus vitamin B1 and warm water. The secondary endpoint was the potential of completing recommended nab-PTX doses. Univariate and multivariable analyses identified independent predictors of CIPN relief, with Cox regression and Kaplan-Meier curves comparing the risk of CIPN relief. A multiple regression analysis was conducted to compare the cumulative nab-PTX doses. The outcome of treatment completion (1560 mg/m² of nab-PTX over six cycles) was assessed by logistic regression, while dose-response relationships were examined by Kaplan-Meier and Cox regression analysis of CIPN-related dose reductions/cessation. An exploratory endpoint was to analyze predictors of FACT/GOG-Ntx, NPS, and QoL by multiple linear regression, adjusting for age, gender, histology, tumor status, and interventions. Descriptive statistics, presented as mean ± standard deviations, summarized demographic data and clinical outcomes (FACT/GOG-Ntx, NPS, QoL scales). Categorical variables were compared using Chi-square or Fisher’s exact tests, while continuous variables were analyzed via ANOVA or nonparametric tests (Mann-Whitney U) for non-normal distributions. Sample size calculation (90% power, α = 0.05) required 207 patients; 227 were enrolled to account for 10% attrition. P < 0.05 was considered statistically significant. Statistical analyses were conducted with SPSS Statistics Software version 26 (IBM) and scripts developed in R version 4.2.1 (R Foundation for Statistical Computing, Vienna, Austria). Results Baseline Characteristics and Clinical Features Of 248 screened CIPN patients, 21 patients were excluded due to declining participation, lost to follow-up, missing data, or dose change considering other reasons. 227 patients with persistent CIPN grading 2–3 were randomly assigned into TCM (n = 72), vitamin B1 (n = 75) or warm water (n = 80) group (Fig. 1 ). At baseline, the three groups were generally well matched demographically and clinically, including prior neuropathy, tumor status and chemotherapy cycles (Table 1 ). For TCM, vitamin B1 and warm water groups, more than half of patients underwent the first treatment line with PTX (50.0% vs 53.3% vs 51.3%); most of the patients received nab-PTX rather than docetaxel (94.4% vs 94.7% vs 96.3%); the proportion of patients receiving treatment other than chemotherapy was 52.8%, 53.3% and 52.5%. In TCM group, 76.4% patients reported CIPN after the first cycle of PTX chemotherapy, and 8.3% patients reported CIPN after the third cycle, which was similar with the other two groups. Analysis by RECIST criteria for tumor status showed similar results of overall response rates (37.5% vs 36.0% vs 35.0%) and disease control rates (90.3% vs 89.3% vs 91.2%). Table 1 Baseline demographics and clinical characteristics of the evaluable population Demographic and clinical characteristics TCM(n = 72) Vitamin B1(n = 75) Warm water(n = 80) P value Gender 0.83 Male 61(84.7) 63(84) 65(81.3) Female 11(15.3) 12(16) 15(18.8) Age (years old) 60.89 ± 9.51 60.72 ± 9.32 60.2 ± 9.44 0.894 BMI (kg/m 2 ) 0.913 <18.5 2(2.8) 2(2.7) 1(1.3) 18.5 ~ 23.9 39(54.2) 39(52) 40(50) ≥ 24.0 31(43.1) 34(45.3) 39(48.8) Diabetes 0.946 No 68(94.4) 70(93.3) 74(92.5) Yes 4(5.6) 5(6.7) 6(7.5) Prior neuropathy 0.862 No 67(93.1) 68(90.7) 73(91.3) Yes 5(6.9) 7(9.3) 7(8.8) Histology 0.988 Adenocarcinoma 22(30.6) 22(29.3) 25(31.3) Squamous cell carcinoma 34(47.2) 36(48) 39(48.8) Neuroendocrine carcinoma 11(15.3) 12(16) 13(16.3) Others 5(6.9) 5(6.7) 3(3.8) Cancer stage 0.916 Ⅲ 13(18.1) 15(20) 14(17.5) Ⅳ 59(81.9) 60(80) 66(82.5) Tumor status 0.989 Progression disease 7(9.7) 8(10.7) 7(8.8) Stable disease 38(52.8) 40(53.3) 45(56.3) Partial response 27(37.5) 27(36) 28(35) ECOG performance score 0.962 0 3(4.2) 3(4) 5(6.3) 1 34(47.2) 35(46.7) 39(48.8) 2 35(48.6) 37(49.3) 36(45) Treatment lines 0.996 1 36(50) 40(53.3) 41(51.3) 2 25(34.7) 24(32) 28(35) 3 9(12.5) 9(12) 8(10) 4 2(2.8) 2(2.7) 3(3.8) Chemotherapy cycles 0.664 5 2(2.8) 3(4) 5(6.3) 6 70(97.2) 72(96) 75(93.8) Types of paclitaxel nab-PTX 68(94.4) 71(94.7) 77(96.3) 0.861 Docetaxel 4(5.6) 4(5.3) 3(3.8) Platinum 0.696 No 18(25) 15(20) 16(20) Yes 54(75) 60(80) 64(80) Immunotherapy 0.943 No 44(61.1) 47(62.7) 48(60) Yes 28(38.9) 28(37.3) 32(40) Antiangiogenic drugs 0.821 No 62(86.1) 63(84) 70(87.5) Yes 10(13.9) 12(16) 10(12.5) Abbreviations: TCM, traditional Chinese medicine; ECOG, Eastern Cooperative Oncology Group; BMI, body mass index; nab-PTX, nanoparticle albumin-bound paclitaxel Assessment of the Severity of CIPN The severity of CIPN for TCM group had no significant difference compared to the other two groups at baseline (Table 2 ). The incidence of CIPN grading 2–3 after two cycles of intervention were significantly lower in TCM group than in vitamin B1 and warm water groups (SPN: 90.3% vs 100.0% vs 100.0%, P < 0.001; MPN: 93.1% vs 100.0% vs 100.0%, P < 0.001). After four cycles of TCM therapy, the proportion of participants with SPN grading 2–3 dropped to 83.3% (60/72) and MPN grading 2–3 dropped to 73.6% (53/72), resulting in more significant distinction between treatment groups with the increasing of intervention cycles (Fig. 2 ). The Kaplan-Meier analysis indicated that the likelihood of CIPN relief compared was significantly higher in TCM group (48.6%) than in vitamin B1 (12%) and warm water group (7.5%) (Fig. 3 A, P < 0.001). The mean time from study entry to first CIPN relief was 9.7, 11.6 and 11.8 weeks for TCM, vitamin B1 and warm water groups (Table 3 , P < 0.001). A multivariable model analysis of CIPN relief correlates found that TCM therapy significantly increased the incidence of CIPN relief (OR = 14.76; 95% CI, 5.39–40.4, P < 0.001), while negative factors were progression disease (OR = 0.13; 95% CI, 0.03–0.68; P = 0.016), stable disease (OR = 0.331; 95% CI, 0.15–0.72; P = 0.005) and antiangiogenic drugs (OR = 0.23; 95% CI, 0.06–0.88, P = 0.032) (Supplementary table 6–7). Further, in a Cox regression analysis to control for CIPN relief time, TCM therapy (HR = 9.76; 95% CI, 4.09–23.31; P < 0.001), progression disease (HR = 0.17; 95% CI, 0.04–0.74; P = 0.018) and stable disease (HR = 0.46; 95% CI, 0.26–0.82; P = 0.008) remained to be significant variables influencing CIPN relief (Supplementary table 8). Table 2 Comparison of CIPN severity grading and variable CIPN-related scales level between treatment groups within four cycles of intervention Time Grade/scales TCM (n = 72) Vitamin B1(n = 75) Warm water(n = 80) P value Grade of SPN Baseline Grade 1 0(0) 0(0) 0(0) 0.793 Grade 2 64(88.9) 66(88) 73(91.3) Grade 3 8(11.1) 9(12) 7(8.8) Cycle 1 Grade 1 2(2.8) 0(0) 0(0) 0.226 Grade 2 66(91.7) 66(88) 71(88.8) Grade 3 4(5.6) 9(12) 9(11.3) Cycle 2 Grade 1 7(9.7) 0(0) 0(0) < 0.001 Grade 2 65(90.3) 67(89.3) 69(86.3) Grade 3 0(0) 8(10.7) 11(13.8) Cycle 3 Grade 1 10(13.9) 0(0) 0(0) < 0.001 Grade 2 62(86.1) 67(89.3) 67(83.8) Grade 3 0(0) 8(10.7) 13(16.3) Cycle 4 Grade 1 12(16.7) 0(0) 0(0) < 0.001 Grade 2 60(83.3) 64(85.3) 63(78.8) Grade 3 0(0) 11(14.7) 17(21.3) Grade of MPN Baseline Grade 1 0(0) 0(0) 0(0) 0.732 Grade 2 50(69.4) 50(66.7) 58(72.5) Grade 3 22(30.6) 25(33.3) 22(27.5) Cycle 1 Grade 1 1(1.4) 0(0) 0(0) 0.001 Grade 2 66(91.7) 52(69.3) 57(71.3) Grade 3 5(6.9) 23(30.7) 23(28.8) Cycle 2 Grade 1 5(6.9) 0(0) 0(0) < 0.001 Grade 2 67(93.1) 56(74.7) 52(65) Grade 3 0(0) 19(25.3) 28(35) Cycle 3 Grade 1 12(16.7) 0(0) 0(0) < 0.001 Grade 2 60(83.3) 52(69.3) 50(62.5) Grade 3 0(0) 23(30.7) 30(37.5) Cycle 4 Grade 1 19(26.4) 0(0) 0(0) < 0.001 Grade 2 53(73.6) 48(64) 49(61.3) Grade 3 0(0) 27(36) 31(38.8) CIPN-related outcomes Baseline FACT/GOG-Ntx 16.69 ± 4.35 15.51 ± 3.41 16.55 ± 4.92 0.183 NPS 23.78 ± 7.69 23.8 ± 7.23 22.93 ± 8.64 0.734 QoL 37.17 ± 5.89 37.65 ± 4.8 37.56 ± 3.39 0.805 Cycle 1 FACT/GOG-Ntx 14.56 ± 3.96 16.15 ± 3.8 16.48 ± 5.11 0.017 NPS 20.1 ± 6.39 23.4 ± 7.26 23.38 ± 8.33 0.009 QoL 39.13 ± 5.52 38.52 ± 4.91 37.6 ± 3.92 0.114 Cycle 2 FACT/GOG-Ntx 13.01 ± 4.04 17.87 ± 4.02 18.19 ± 5.09 < 0.001 NPS 18.69 ± 6.55 24.04 ± 6.63 25.23 ± 8.94 < 0.001 QoL 40.71 ± 5.71 38.31 ± 4.8 37.14 ± 3.56 < 0.001 Cycle 3 FACT/GOG-Ntx 12.03 ± 3.96 19.01 ± 3.87 20.06 ± 4.88 < 0.001 NPS 17.49 ± 6.01 26.03 ± 6.27 26.73 ± 8.26 < 0.001 QoL 42.03 ± 5.82 36.85 ± 4.85 35.2 ± 4.01 < 0.001 Cycle 4 FACT/GOG-Ntx 11.5 ± 3.79 20.43 ± 3.91 22.41 ± 6.17 < 0.001 NPS 16.75 ± 5.62 27.71 ± 6.3 29.24 ± 9.22 < 0.001 QoL 42.6 ± 5.87 36.04 ± 4.72 33.56 ± 4.27 < 0.001 Abbreviations: CIPN, chemotherapy-induced peripheral neuropathy; TCM, traditional Chinese medicine; SPN, sensory peripheral neuropathy; MPN, motor peripheral neuropathy; FACT/GOG-Ntx, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity; NPS, Neuropathy Pain Scale; QoL, Quality of Life Table 3 Efficacy outcomes of TCM intervention in CIPN relief and paclitaxel dose reductions/cessation compared to vitamin B1 and warm water Outcome of paclitaxel TCM(n = 72) Vitamin B1(n = 75) Warm water(n = 80) P value CIPN relief < 0.001 No 37(51.4) 66(88) 74(92.5) Yes 35(48.6) 9(12) 6(7.5) Relief time (weeks) 9.72 ± 2.83 11.63 ± 1.23 11.8 ± 0.79 < 0.001 Dose reductions/cessation of paclitaxel 0.001 No 61(84.7) 53(70.7) 46(57.5) Yes 11(15.3) 22(29.3) 34(42.5) Time of dose reductions/cessation (weeks) 11.08 ± 2.45 10.62 ± 2.86 9.66 ± 3.39 0.011 Dose reductions/cessation cycles < 0.001 0 61(84.7) 53(70.7) 46(57.5) 1 0(0) 1(1.3) 5(6.3) 2 1(1.4) 5(6.7) 0(0) 3 1(1.4) 7(9.3) 17(21.3) 4 9(12.5) 9(12) 12(15) Outcomes of nab-PTX TCM(n = 68) Vitamin B1 (n = 71) Warm water (n = 77) P value Cumulative dose of nab-PTX (mg/m 2 ) 1528.87 ± 81.71 1490.97 ± 124.81 1459.45 ± 134.97 0.002 Relative dose intensity of nab-PTX 0.98 ± 0.05 0.96 ± 0.08 0.94 ± 0.09 0.002 Abbreviations: CIPN, chemotherapy-induced peripheral neuropathy; TCM, traditional Chinese medicine; nab-PTX, nanoparticle albumin-bound paclitaxel Evaluation of CIPN-related Symptoms and QoL Patient-reported neurological assessment outcomes evaluated by FACT/GOG-Ntx, NPS and QoL scales showed similar neuropathic burden between treatment groups at baseline (Table 2 ). FACT/GOG-Ntx decreased from 16.7 at baseline to 11.5 after four cycles of TCM therapy, with NPS reduced from 23.8 at baseline to 16.8. There were 45.8% (33/72) and 56.9% (41/72) of patients who had at least a 30% reduction in FACT/GOG-Ntx and NPS from baseline to the end of intervention, considered responsive to TCM therapy. However, these two scales remained increasing in the other two groups, resulting in significant differences between treatment groups after four cycles of intervention (FACT/GOG-Ntx: 11.5 vs 20.4 vs 22.4, P < 0.001; NPS: 16.8 vs 27.7 vs 29.2, P < 0.001). There was no significant difference in the mean QoL score at baseline for TCM, vitamin B1 and warm water groups (37.2 vs 37.7 vs 37.6, P = 0.805). QoL score increased after four cycles of TCM therapy, indicating better physical and emotional well-being, while both vitamin B1 and warm water exhibited limited efficacy in improving patients’ QoL (42.6 vs 36.0 vs 33.6, P < 0.001). Figure 4 displayed the distinction of these scales between patient groups became more significant with the increasing of intervention cycles. Adverse Events Associated with TCM Our study showed one patient had transient mild skin itching after hands and feet immersion, but symptoms were relieved without TCM intervention. No severe adverse events associated with the Qufenghuoxue formula were reported, including skin eruption, bruising, and local persistent pain. One patient had papules on skin in vitamin B1 group, which were relieved with antiallergic treatment. No patients withdrew from the study due to intolerance. Cumulative Dose of Paclitaxel The rate of PTX dose reductions or cessation as a result of CIPN was lower in TCM group than in vitamin B1 and warm water groups (15.3% vs 29.3% vs 42.5%; P = 0.001) (Table 3 ). Owing to the small number of patients receiving docetaxel, we focus on the cumulative dose of nab-PTX analyzed. The mean cumulative dose of nab-PTX was 1528.9 mg/m 2 , 1491.0 mg/m 2 and 1459.5 mg/m 2 in TCM, vitamin B1 and warm water groups, resulting in the significant difference of relative dose intensity of nab-PTX (0.98 vs 0.96 vs 0.94, P = 0.002). The Kaplan-Meier analysis showed that TCM group had higher likelihood of completing the recommended dose of nab-PTX (1560 mg/m²) than the other two groups (83.8% vs 74.6% vs 59.7%, P = 0.0034) (Fig. 3 B). In a Cox proportional hazards model, we estimated the hazard ratio (HR) of dose reductions or cessation due to CIPN (Supplementary table 9). With warm water as a reference, the univariate HR was 0.36 (95% CI, 0.18–0.72; P = 0.004) for TCM and 0.59 (95% CI, 0.33–1.05; P = 0.074) for vitamin B1. The multivariate HR, adjusted for age and tumor status, was 0.34 (95% CI: 0.17–0.67, P = 0.002) and 0.56 (95% CI: 0.31–1.00, P = 0.053). Factors Associated with CIPN-related Outcomes The multivariable model found a significant association with FACT/GOG- Ntx (F = 11.798; P < 0.001; R 2 = 0.605) (Supplementary table 10). Factors associated with lower FACT/GOG-Ntx were the Qufenghuoxue formula therapy (β = -11.17; 95% CI, -12.63 to -9.72; P < 0.001), vitamin B1 therapy (β = -2.25; 95% CI, -3.68 to -0.81; P = 0.002), age (β = 0.15; 95% CI, 0.07 to 0.23; P < 0.001), partial response (β = -2.64; 95% CI, -4.91 to -0.38; P = 0.022), and stable disease (β = −2.82; 95% CI, − 5.01 to − 0.62; P = 0.012). These factors above explained 60.5% of the total variance in FACT/GOG-Ntx. Multivariable analysis also identified the factors that were associated with NPS (F = 8.044; P < 0.001; R 2 = 0.511) and QoL (F = 8.942; P < 0.001; R 2 = 0.538). The independent variables included CIPN intervention, tumor histology and treatment lines. Patients who received TCM therapy were more inclined to have lower NPS (β = −12.57; 95% CI, − 14.77 to − 10.36; P < 0.001) and better QoL (β = 9.11; 95% CI, 7.64 to 10.58; P < 0.001). Patients with the 2nd treatment line had similar results in terms of NPS (β = −11.39; 95% CI, − 17.20 to − 5.58; P < 0.001) and QoL scale (β = 8.61; 95% CI, 4.75 to 12.48; P < 0.001). Discussion CIPN is one of the dose-limiting toxicity resulting in chemotherapy dose reductions/cessation and impaired daily function. Hands and feet immersion with Qufenghuoxue formula could effectively relieve CIPN-related symptoms evaluated by FACT/GOG-Ntx and NPS scales, which might increase the likelihood of CIPN relief and improve quality of life. This strategy also increased the potential of completing the recommended nab-PTX dose with fewer dose modifications. We have established that it is a safe and feasible adjunctive treatment for advanced lung cancer patients developing moderate-to- severe CIPN. As PTX cumulative dose increased, CIPN-related symptoms worsened in the vitamin B1 and warm water groups, negatively impacting QoL. In contrast, Qufenghuoxue formula therapy significantly reduced FACT/GOG-NTx and NPS scores, indicating alleviated neuropathic symptoms. Our study indicated that Qufenghuoxue formula significantly reduced the incidence of CIPN grading 2–3 compared to vitamin B1 and warm water, with effects becoming more pronounced over multiple cycles. It also shortened the mean time to CIPN relief, and increased the likelihood of CIPN relief by 48.6% after four intervention cycles, demonstrating its efficacy and safety. Patients with partial tumor response benefited more from Qufenghuoxue formula than those with stable or progressive disease. It might be due to lower tumor burden and better overall health, qualifying patients to deal with adverse effects of chemotherapy with sufficient function of vital organs. Regression analysis confirmed its significant therapeutic benefits, with partial tumor response correlating with CIPN relief. This result was also consistent with the multivariable analysis of positive correlates promoting CIPN relief. Post-treatment follow-up is needed to determine if Qufenghuoxue formula provides long-term benefit for CIPN relief. Previous research suggested that vitamin B1 might protect patients against the onset and development of CIPN through preventing nerve dysfunction and nerve damage 18 – 20 . Patients receiving vitamin B1 during chemotherapy had a lower CIPN rate after one month treatment than those without vitamin B1 (42.9% vs 63.8%, P < 0.05) 18 . An explanation for limited efficacy in our vitamin B1 group might be the short trial duration of intervention or insufficient symptom improvement to affect CIPN severity grading. Longer follow-up is necessary to assess its potential benefits on subjective symptoms and objective responses that require reversal of neuropathy process. Notably, the efficacy of assessment scales varied in clinical trials, which may be a result of discrepancies between clinician- and patient-reported outcomes with minimal agreement and variation by CIPN grade 21 . Our patient-reported outcome measures reflect a real-world setting of advanced lung cancer patients. PTX dose reductions or complete cessation is implemented among patients with CIPN-related symptoms 22 . Both dose reductions and treatment cessation due to CIPN negatively impact survival, considerably 23 , 24 . We took the cumulative nab-PTX dose as a secondary endpoint to reflect its significant influence on treatment outcomes. 83.8% of patients receiving Qufenghuoxue formula in our study completed the recommended nab-PTX dose, compared to 74.6% and 59.7% in vitamin B1 and warm water groups. The effects of Qufenghuoxue formula on cancer treatment showed that it increased the likelihood of completing recommended nab-PTX doses, leading to higher cumulative doses and relative dose intensity. Cox regression further confirmed the reduced risk of dose reductions/cessation. Sato et al. reported that cooling group had lower incidence of moderate-to-high CIPN than control group without affecting paclitaxel dose reductions in cancer patients 25 . Differences in treatment regimens, histology, chemotherapy cycles and cumulative doses might explain the discrepancy. As a new paclitaxel drug encapsulated with liposomes, nab-PTX can improve bioavailability and reduce toxicities such as myelosuppression due to lower bio-disposition in vital organs 26 , 27 . However, a recent study showed that nab-PTX was associated with more severe CIPN than traditional taxanes 28 . Thus, strategies such as Qufenghuoxue formula to manage CIPN and maintain optimal nab-PTX dosing level are of critical clinical importance. No pharmacologic agent could conclusively prevent CIPN in over 40 randomized trials involving anticonvulsants, antidepressants, vitamins and minerals 29 . Paclitaxel causes microtubule disruption in peripheral nerves, further impairing axonal transport, altering homeostasis and triggering CIPN 4 , 30 . CIPN is ascribed to “blockage syndrome” or “Bi Zheng” in TCM theory 9 . Firstly, Qufenghuoxue formula therapy may enhance microcirculation and neurotransmitter transmission to relieve “blockage syndrome”. Secondly, it may stimulate meridian points on limb extremities through transdermal absorption in order to improve peripheral blood flow and alleviate sensory disturbance. Thirdly, Qufenghuoxue formula contains nine active compounds (e.g., Huangqi for nerve development and regeneration, Guizhi for dispersing blockage, Jixueteng for relieving blood stasis, Xixiancao for anti-inflammatory/antioxidant effect with anti-tumor activities). They collectively reduce blood viscosity, support nerve repair, and mitigate nerve damage. In contrast to oral or intravenous drugs, topical administration avoids potential toxicity of liver, kidney and gastrointestinal tract. Further research is needed to clarify its molecular mechanisms. This is the first prospective and randomized study to evaluate the efficacy and safety for TCM therapy in CIPN management among advanced lung cancer patients. Qufenghuoxue formula can relieve CIPN-related symptoms and enable optimal nab-PTX dosing. However, some limitations must be acknowledged. The observation period of 4–6 chemotherapy cycles precludes assessment of long-term benefits of intervention. Long-term course with post-treatment period may determine whether Qufenghuoxue formula can reduce CIPN severity permanently and improve therapeutic outcomes. As multi-center analysis was interrupted by the outbreak of COVID-19 virus infection, originating from a single center might limit the generalizability of these results. Finally, we should further consider the effect of other potential confounding factors (e.g., nutritional or dietary supplements, patients’ lifestyle) in multicenter validation. Conclusion As a medicine for external use, Qufenghuoxue formula therapy is demonstrated to be feasible and well-tolerated in advanced lung cancer patients with PTX-related peripheral neuropathy. This strategy reduces CIPN severity grading, accelerates symptom relief, and improves quality of life. It also has the potential to prevent dose-limiting events and be supportive for completing the recommended nab-PTX dosing. These promising results warrant further investigation into long-term benefits of this valuable candidate for CIPN management. Abbreviations nab-PTX, nanoparticle albumin-bound paclitaxel; TCM, traditional Chinese medicine; CIPN, chemotherapy-induced peripheral neuropathy; NCI-CTCAE, National Cancer Institute-Common Terminology Criteria for Adverse Events; FACT/GOG-Ntx, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity; NPS, Neuropathy Pain Scale; RECIST, Response Evaluation Criteria In Solid Tumors; QoL, Quality of Life; SPN, sensory peripheral neuropathy; MPN, motor peripheral neuropathy; ECOG, Eastern Cooperative Oncology Group; BMI, body mass index; IQR, interquartile range; OR, odds ratio; SD, standard deviation; HR, hazard ratio; CI, confidence interval. Declarations Acknowledgments The authors thank the patients who have participated in this study. Disclosure of competing interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethics approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Zhongshan Hospital, Fudan University (No. B2021-257R). Consent to participate and publish All patients signed informed consent regarding participating this trial and publishing their data. Consent for publication All authors have read and approved the revised version submitted and published. Author Contributions All authors have made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; agreed on the journal to which the article has been submitted; and agreed to be accountable for all aspects of the work. Funding This study was supported by the Science and Technology Commission of Shanghai Municipality (grant number: 20DZ2261200, 20DZ2254400); the Construction of Multidisciplinary Cooperative Diagnosis and Treatment for Severe Pneumonia (grant number: W2020-013); the Mechanisms of Antibiotic Resistance in Severe Pneumonia Treated with Traditional Chinese and Western Medicine (grant number: ZY (2021-2023)-0207-01); Shanghai Municipal Key Clinical Specialty (grant number: shslczdzk02201); National Natural Science Foundation of China (grant number: 82170110); Fujian Provincial Department of Science and Technology (grant number: 2022D014), Shanghai Pujiang Program (grant number: 20PJ1402400) and Quzhou Science and Technology Bureau Programme Project (grant number: 2023K112). Data Availability Statement The raw data supporting the conclusions of this article will be made available from the corresponding authors under reasonable requests. References Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA Cancer J Clin 2023; 73: 17–48. 2023/01/13. DOI: 10.3322/caac.21763 . NCCN. Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Non-Small Cell Lung Cancer. Version 1. 2023. NCCN. Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Small Cell Lung Cancer. Version 1. 2023. Park SB, Goldstein D, Krishnan AV, et al. Chemotherapy-induced peripheral neurotoxicity: a critical analysis. CA Cancer J Clin 2013; 63: 419–437. 2014/03/05 . DOI: 10.3322/caac.21204. Seretny M, Currie GL, Sena ES, et al. Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. Pain 2014; 155: 2461–2470. 2014/09/28. DOI: 10.1016/j.pain.2014.09.020 . Gutiérrez-Gutiérrez G, Sereno M, Miralles A, et al. Chemotherapy-induced peripheral neuropathy: clinical features, diagnosis, prevention and treatment strategies. Clin Transl Oncol 2010; 12: 81–91. 2010/02/17. DOI: 10.1007/S12094-010-0474-z . Starobova H and Vetter I. Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy. Front Mol Neurosci 2017; 10: 174. 2017/06/18. DOI: 10.3389/fnmol.2017.00174 . Kacem H, Cimini A, d'Angelo M, et al. Molecular and Cellular Involvement in CIPN. Biomedicines 2024; 12 2024/04/27. DOI: 10.3390/biomedicines12040751 . Yue Shi and Li. C. Advances of Chinese and Western Medicine in Treating Chemotherapy-induced Peripheral Neurotoxicity. Clinical Journal of Traditional Chinese Medicine 2017; 29: 327–330. Ma F and Xu B. Expert Consensus Committee on the Management of Taxanes-induced Peripheral Neuropathy. Expert consensus on standardized management of taxane-related peripheral neuropathy. Chinese Journal of the Frontiers of Medical Science 2020; 12: 41–51. Dai H. The Clinical Study of Chinese Medicine Fumigation and Wash Therapy in the Treatment of Peripheral Neurotoxicity Induced by Taxol. Chinese Medicine Modern Distance Education of China 2017; 15: 96–98. Chinese_Pharmacopoeia_Commission. Pharmacopoeia of the People’s Republic of China. Beijing : People’s Medical Publishing House 2020. Bonhof CS, Mols F, Vos MC, et al. Course of chemotherapy-induced peripheral neuropathy and its impact on health-related quality of life among ovarian cancer patients: A longitudinal study. Gynecol Oncol 2018; 149: 455–463. 2018/04/02. DOI: 10.1016/j.ygyno.2018.03.052 . Galer BS and Jensen MP. Development and preliminary validation of a pain measure specific to neuropathic pain: the Neuropathic Pain Scale. Neurology 1997; 48: 332–338. 1997/02/01. DOI: 10.1212/wnl.48.2.332 . Jensen MP, Friedman M, Bonzo D, et al. The validity of the neuropathic pain scale for assessing diabetic neuropathic pain in a clinical trial. Clin J Pain 2006; 22: 97–103. 2005/12/13. DOI: 10.1097/01.ajp.0000173018.64741.62 . Hung HW, Liu CY, Chen HF, et al. Impact of Chemotherapy-Induced Peripheral Neuropathy on Quality of Life in Patients with Advanced Lung Cancer Receiving Platinum-Based Chemotherapy. Int J Environ Res Public Health 2021; 18 2021/06/03 . DOI: 10.3390/ijerph18115677. Mizrahi D, Park SB, Li T, et al. Hemoglobin, Body Mass Index, and Age as Risk Factors for Paclitaxel- and Oxaliplatin-Induced Peripheral Neuropathy. JAMA Netw Open 2021; 4: e2036695. 2021/02/16 . DOI: 10.1001/jamanetworkopen.2020.36695. Jin L, Zhang Y and Yang W. Chemotherapy-induced peripheral neuropathy among patients with ovarian cancer. Int J Gynaecol Obstet 2020; 149: 303–308. 2020/03/07 . DOI: 10.1002/ijgo.13137. Schloss J and Colosimo M. B Vitamin Complex and Chemotherapy-Induced Peripheral Neuropathy. Curr Oncol Rep 2017; 19: 76. 2017/10/07. DOI: 10.1007/s11912-017-0636-z . Schloss JM, Colosimo M, Airey C, et al. A randomised, placebo-controlled trial assessing the efficacy of an oral B group vitamin in preventing the development of chemotherapy-induced peripheral neuropathy (CIPN). Support Care Cancer 2017; 25: 195–204. 2016/09/11 . DOI: 10.1007/s00520-016-3404-y. Nyrop KA, Deal AM, Reeder-Hayes KE, et al. Patient-reported and clinician-reported chemotherapy-induced peripheral neuropathy in patients with early breast cancer: Current clinical practice. Cancer 2019; 125: 2945–2954. 2019/05/16 . DOI: 10.1002/cncr.32175. Dorsey SG, Kleckner IR, Barton D, et al. The National Cancer Institute Clinical Trials Planning Meeting for Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy. J Natl Cancer Inst 2019; 111: 531–537. 2019/02/05 . DOI: 10.1093/jnci/djz011. Chirivella I, Bermejo B, Insa A, et al. Optimal delivery of anthracycline-based chemotherapy in the adjuvant setting improves outcome of breast cancer patients. Breast Cancer Res Treat 2009; 114: 479–484. 2008/05/09 . DOI: 10.1007/s10549-008-0018-1. Winer EP, Berry DA, Woolf S, et al. Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: cancer and leukemia group B trial 9342. J Clin Oncol 2004; 22: 2061–2068. 2004/06/01. DOI: 10.1200/jco.2004.08.048 . Sato J, Mori M, Nihei S, et al. The effectiveness of regional cooling for paclitaxel-induced peripheral neuropathy. J Pharm Health Care Sci 2016; 2: 33. 2016/11/29. DOI: 10.1186/s40780-016-0067-2 . Yang T, Cui FD, Choi MK, et al. Enhanced solubility and stability of PEGylated liposomal paclitaxel: in vitro and in vivo evaluation. Int J Pharm 2007; 338: 317–326. 2007/03/21. DOI: 10.1016/j.ijpharm.2007.02.011 . Zang X, Lee JB, Deshpande K, et al. Prevention of paclitaxel-induced neuropathy by formulation approach. J Control Release 2019; 303: 109–116. 2019/04/15. DOI: 10.1016/j.jconrel.2019.04.013 . Mo H, Yan X, Zhao F, et al. Association of Taxane Type With Patient-Reported Chemotherapy-Induced Peripheral Neuropathy Among Patients With Breast Cancer. JAMA Netw Open 2022; 5: e2239788. 2022/11/03 . DOI: 10.1001/jamanetworkopen.2022.39788. Loprinzi CL, Lacchetti C, Bleeker J, et al. Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update. J Clin Oncol 2020; 38: 3325–3348. 2020/07/15 . DOI: 10.1200/jco.20.01399. Verweij J, Clavel M and Chevalier B. Paclitaxel (Taxol) and docetaxel (Taxotere): not simply two of a kind. Ann Oncol 1994; 5: 495–505. 1994/07/01. DOI: 10.1093/oxfordjournals.annonc.a058903 . Additional Declarations No competing interests reported. Supplementary Files Supplementarydata.docx Cite Share Download PDF Status: Published Journal Publication published 22 Dec, 2025 Read the published version in Supportive Care in Cancer → Version 1 posted Editorial decision: Revision requested 20 Oct, 2025 Reviews received at journal 16 Oct, 2025 Reviews received at journal 29 Sep, 2025 Reviewers agreed at journal 25 Sep, 2025 Reviewers agreed at journal 25 Sep, 2025 Reviewers agreed at journal 17 Jul, 2025 Reviewers invited by journal 13 Jul, 2025 Editor assigned by journal 08 Jul, 2025 Submission checks completed at journal 05 Jun, 2025 First submitted to journal 02 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6802916","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":485253179,"identity":"a3f2acc8-6b1d-408b-a9cb-7e7ad336b550","order_by":0,"name":"Yijun Song","email":"","orcid":"","institution":"Zhongshan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yijun","middleName":"","lastName":"Song","suffix":""},{"id":485253180,"identity":"681153eb-b182-4740-a68b-49ba94348247","order_by":1,"name":"Zhidan Hua","email":"","orcid":"","institution":"Quzhou City People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhidan","middleName":"","lastName":"Hua","suffix":""},{"id":485253181,"identity":"cb14b898-9a6a-48ea-b3fc-61b11bbf110d","order_by":2,"name":"Mengting Sun","email":"","orcid":"","institution":"Zhongshan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mengting","middleName":"","lastName":"Sun","suffix":""},{"id":485253182,"identity":"be9dcf8a-8104-426d-9df6-a0d07682a9ef","order_by":3,"name":"Nuo Xu","email":"","orcid":"","institution":"Zhongshan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Nuo","middleName":"","lastName":"Xu","suffix":""},{"id":485253183,"identity":"4907ab4d-432f-4ea0-9597-5c6a874f2e73","order_by":4,"name":"Xinyuan Lu","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Xinyuan","middleName":"","lastName":"Lu","suffix":""},{"id":485253184,"identity":"b7e509c5-24e7-43c6-8f70-5a4343a31639","order_by":5,"name":"Dawei Yang","email":"","orcid":"","institution":"Zhongshan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dawei","middleName":"","lastName":"Yang","suffix":""},{"id":485253185,"identity":"af7ad497-40d4-44bf-90ff-b2127b0cd01c","order_by":6,"name":"Xixi Gu","email":"","orcid":"","institution":"Zhongshan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xixi","middleName":"","lastName":"Gu","suffix":""},{"id":485253186,"identity":"495cdfd0-10ba-43c3-97dc-fe2f16b65eb0","order_by":7,"name":"Yuanlin Song","email":"","orcid":"","institution":"Zhongshan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuanlin","middleName":"","lastName":"Song","suffix":""},{"id":485253187,"identity":"7b3c8877-af79-4aaf-acf5-e5431f28e62a","order_by":8,"name":"Jun She","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABC0lEQVRIie2Qv0oDQRCH5wjsNXtcOyHivsIeFkEQ8iobAqZJsLNeCWyb9oKFr2Cp3YYFq5D6iis8hNRXCYEUzqkxEtxca7Ef7D+Yj/3NAAQC/xH8Wud0sObNAToaIt2uXPwovKlvVYih/lagVRH3MwuXphw/zC17rXfl2SBe6mj7BKLvUWT5oqBrNtO7XMXZwmw450PdSVaQPXt+kjiRpLjpDNP3XqId9UJKZEBJ6wmW39SNMmapZT2+IyWtKNgJBYoJNIrioEhhpCCNIjmhyOJaWly7LEfFup+9FJV2icHs0RtsVL3hrROCJoY0sUE8Hy2rrbkS3mCEw8Pd7nf8s3RPVB8rgUAgEPjNBxpJV3v0TJqUAAAAAElFTkSuQmCC","orcid":"","institution":"Zhongshan Hospital","correspondingAuthor":true,"prefix":"","firstName":"Jun","middleName":"","lastName":"She","suffix":""}],"badges":[],"createdAt":"2025-06-02 14:08:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6802916/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6802916/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00520-025-10273-7","type":"published","date":"2025-12-22T15:57:46+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":87033272,"identity":"b6967058-e3a4-45ce-b6b5-9ebebfa2c29a","added_by":"auto","created_at":"2025-07-18 13:04:33","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":42395,"visible":true,"origin":"","legend":"\u003cp\u003eStudy design. CIPN, chemotherapy-induced peripheral neuropathy; TCM, traditional Chinese medicine\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6802916/v1/06ab4f8ad20bc07ebdbc7fa7.png"},{"id":87035177,"identity":"60da2c23-9717-4f60-bfa6-5116af78191f","added_by":"auto","created_at":"2025-07-18 13:12:33","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":32976,"visible":true,"origin":"","legend":"\u003cp\u003ePrevalence of (A) sensory peripheral neuropathy and (B) motor peripheral neuropathy with different severity grading at each study visit in TCM, vitamin B1 and warm water groups. TCM, traditional Chinese medicine\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6802916/v1/fa8b049ded847bde45723c09.png"},{"id":87035178,"identity":"4de32885-ee04-4b21-9771-ce631d20283d","added_by":"auto","created_at":"2025-07-18 13:12:33","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":18768,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of CIPN relief (A) and cumulative dose of nab-PTX (B) between TCM, vitamin B1 and warm water groups by Kaplan-Meier curves. TCM, traditional Chinese medicine; CIPN, chemotherapy-induced peripheral neuropathy; nab-PTX, nanoparticle albumin-bound paclitaxel\u003c/p\u003e","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6802916/v1/55d75a88c8283afb52b39358.png"},{"id":87033271,"identity":"02d6c529-7492-40c6-b0d4-a5d6ce37440c","added_by":"auto","created_at":"2025-07-18 13:04:33","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":23358,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of CIPN-related outcomes including FACT/GOG-Ntx, NPS and Quality of Life (QoL) between TCM, vitamin B1 and warm water groups. TCM, traditional Chinese medicine; CIPN, chemotherapy-induced peripheral neuropathy; FACT/GOG-Ntx, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity; NPS, Neuropathy Pain Scale\u003c/p\u003e","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6802916/v1/3d1cd23dc08663c0304b3707.png"},{"id":99172307,"identity":"3217be55-69c3-4eca-8434-0b9975c73a7a","added_by":"auto","created_at":"2025-12-29 16:07:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1490741,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6802916/v1/07f05f32-a3a6-4f5d-bb21-aec0092138b4.pdf"},{"id":87036342,"identity":"053e3d63-57cb-4857-a3b4-4e9018f83bf2","added_by":"auto","created_at":"2025-07-18 13:20:33","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":55067,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarydata.docx","url":"https://assets-eu.researchsquare.com/files/rs-6802916/v1/78aa21359d7e13d7a2e2394f.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Efficacy and Safety of Traditional Chinese Medicine Qufenghuoxue Formula on Peripheral Neuropathy Induced by Paclitaxel in Advanced Lung Cancer：A Randomized Clinical Trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePaclitaxel (PTX) is considered to be one of the main chemotherapy for advanced lung cancer\u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. However, chemotherapy-induced peripheral neuropathy (CIPN), including sensory peripheral neuropathy (SPN) and motor peripheral neuropathy (MPN), is one of the most dose-limiting side effects of PTX administration\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Up to 90% of cancer patients develop CIPN during or after chemotherapy with 30% continuing to suffer permanently\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. These side effects frequently lead to chemotherapy dose reduction or cessation, worsening treatment outcomes and quality of life⁷. Currently, there are no treatment strategies that effectively prevent or attenuate CIPN-related symptoms, leaving disease management largely symptomatic and palliative.\u003c/p\u003e\u003cp\u003ePatients may develop acute neurological symptoms within hours or days of chemotherapy, persisting for months⁷. CIPN significantly impacts quality of life and survival, necessitating effective management to alleviate symptoms and maintain optimal paclitaxel dosing. Current treatments, including narcotics, antidepressants, anticonvulsants, vitamins, and acupuncture, provide limited relief⁸. While vitamin B, cryotherapy, and gradient pressure show potential in reducing CIPN risk, conclusive evidence is still lacking⁹⁻\u0026sup1;\u0026sup1;. Notably, moderate to severe CIPN continues to plague patients and medical fraternity, driving the need for innovative therapies\u0026sup1;\u0026sup2;.\u003c/p\u003e\u003cp\u003eThe pathophysiology of CIPN involves microtubule disruption, neuroinflammation, oxidative stress, and homeostasis imbalance\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. In Traditional Chinese Medicine (TCM) theory, CIPN is ascribed to \"blockage syndrome\" (\u0026ldquo;Bi Zheng\u0026rdquo;)\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Hands and feet immersion of TCM may alleviate neuropathic symptoms by stimulating meridian points and promoting transdermal drug absorption\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. For example, Qufenghuoxue formula may enhance neurotransmitter activity and microcirculation to address \"blockage syndrome\" via immersion. TCM is widely accessible, well-tolerated, and rarely causes severe side effects, aligning with its principle of external treatment for internal disorders\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. This study compares the efficacy and safety of Qufenghuoxue formula, vitamin B1, and warm water in treating CIPN among advanced lung cancer patients.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatients and study design\u003c/h2\u003e\u003cp\u003eThe investigator-initiated, open-label randomized study evaluated the efficacy and safety of hands and feet immersion with Qufenghuoxue formula for CIPN among advanced lung cancer patients. A total of 227 patients developing CIPN after PTX-based chemotherapy were enrolled. Both PTX (nanoparticle albumin-bound paclitaxel (nab-PTX) 260 mg/m\u003csup\u003e2\u003c/sup\u003e or docetaxel 75 mg/m\u003csup\u003e2\u003c/sup\u003e) and platinum agents were given every three weeks. The inclusion criteria include: (1) Advanced lung cancer (pathologically confirmed at Zhongshan Hospital); (2) PTX-induced CIPN (National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading 2\u0026ndash;3); (3) Willing to attend visits and complete questionnaires every three weeks; (4) Age\u0026thinsp;\u0026gt;\u0026thinsp;18 years old, life expectancy\u0026thinsp;\u0026ge;\u0026thinsp;6 months; (5) Eastern Cooperative Oncology Group (ECOG) performance score (PS) 0\u0026ndash;2. Patients who had skin damage on hands and feet or failed to complete the questionnaires were excluded from the study.\u003c/p\u003e\u003cp\u003e227 advanced lung cancer patients with CIPN were randomized into three groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e): (1) TCM group: Qufenghuoxue formula (nine herbs, see Supplementary table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) for hands and feet immersion (30 minutes, twice daily); (2) Vitamin B1 group: Oral vitamin B1 (10 mg, three times daily); (3) Warm water group: Hands and feet immersion in 40℃ water (30 minutes, twice daily). The quality of herbs complied with the 2020 Chinese pharmacopoeia, and safety tests for heavy metals, microbial contamination and residual pesticides met national standards\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. PTX dose reductions or discontinuation were considered for severe adverse events, including CIPN; patients were censored if dosing changed for non-neuropathy reasons. Demographic and clinical data were collected from May 2023 to August 2024 at Zhongshan Hospital, Fudan University. The study (B2021-257R, ChiCTR2300069949) complied with the Declaration of Helsinki and was approved by the hospital\u0026rsquo;s ethics committee. All participants provided informed consent.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003ePeripheral Neuropathy Assessments\u003c/h3\u003e\n\u003cp\u003eNeuropathy assessments were conducted at baseline and every three weeks before chemotherapy. The severity of SPN and MPN was evaluated by NCI-CTCAE version 5.0 (Grade 1\u0026ndash;5) (Supplementary table 2). CIPN relief was defined as a reduction in SPN or MPN severity grading, with relief time recorded from study entry to the first occurrence of CIPN relief. Subjective neuropathy symptoms were evaluated using:\u003c/p\u003e\u003cp\u003e(1) Functional Assessment of Cancer Therapy/Gynecologic Oncology Group\u0026ndash;Neurotoxicity (FACT/GOG-NTx) (score 0\u0026ndash;44; higher\u0026thinsp;=\u0026thinsp;worse neuropathic symptoms): Ntx subscale contains eleven neurotoxicity items assessing SPN, MPN, hearing neuropathy, and neuropathic dysfunction associated with neurotoxicity symptoms\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e (Supplementary Table\u0026nbsp;3).\u003c/p\u003e\u003cp\u003e(2) Neuropathy Pain Scale (NPS) (score 0\u0026ndash;100; higher\u0026thinsp;=\u0026thinsp;worse neuropathic pain): NPS utilizes self-report visual analogue scales to quantify neuropathic pain intensity and distinguish it from non-neuropathic pain\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e (Supplementary Table\u0026nbsp;4).\u003c/p\u003e\u003cp\u003eQuality of Life (QoL) was assessed through a 12-item scale (score 0\u0026ndash;60; higher\u0026thinsp;=\u0026thinsp;better QoL), covering appetite, mental state, pain, daily activities, and side effects of treatment\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e (Supplementary Table\u0026nbsp;5).\u003c/p\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eDemographic and clinical data were collected from medical recording system, including age, gender, weight, height, ECOG PS, histology, tumor stage, tumor status, treatment lines, chemotherapy modalities, and cumulative PTX dose. Tumor status was assessed periodically via tumor markers and CT scans. Relative dose intensity of PTX was calculated as (cumulative administered dose / planned dose) \u0026times; 100%\u003csup\u003e17\u003c/sup\u003e. Patients self-reported FACT/GOG-Ntx, NPS, and QoL scales, with physicians assisting older or illiterate patients. During follow-ups, physicians recorded PTX doses, dose adjustments, CIPN grade, adverse effects, and tumor responses assessed by Response Evaluation Criteria in Solid Tumors v1.1. Pulmonologists independently adjusted chemotherapy based on toxicity. All dose modifications, delays, or cessations were documented.\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eThe primary endpoint was the efficacy and safety of Qufenghuoxue formula versus vitamin B1 and warm water. The secondary endpoint was the potential of completing recommended nab-PTX doses. Univariate and multivariable analyses identified independent predictors of CIPN relief, with Cox regression and Kaplan-Meier curves comparing the risk of CIPN relief. A multiple regression analysis was conducted to compare the cumulative nab-PTX doses. The outcome of treatment completion (1560 mg/m\u0026sup2; of nab-PTX over six cycles) was assessed by logistic regression, while dose-response relationships were examined by Kaplan-Meier and Cox regression analysis of CIPN-related dose reductions/cessation. An exploratory endpoint was to analyze predictors of FACT/GOG-Ntx, NPS, and QoL by multiple linear regression, adjusting for age, gender, histology, tumor status, and interventions.\u003c/p\u003e\u003cp\u003eDescriptive statistics, presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations, summarized demographic data and clinical outcomes (FACT/GOG-Ntx, NPS, QoL scales). Categorical variables were compared using Chi-square or Fisher\u0026rsquo;s exact tests, while continuous variables were analyzed via ANOVA or nonparametric tests (Mann-Whitney U) for non-normal distributions. Sample size calculation (90% power, α\u0026thinsp;=\u0026thinsp;0.05) required 207 patients; 227 were enrolled to account for 10% attrition. \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Statistical analyses were conducted with SPSS Statistics Software version 26 (IBM) and scripts developed in R version 4.2.1 (R Foundation for Statistical Computing, Vienna, Austria).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eBaseline Characteristics and Clinical Features\u003c/h2\u003e\u003cp\u003eOf 248 screened CIPN patients, 21 patients were excluded due to declining participation, lost to follow-up, missing data, or dose change considering other reasons. 227 patients with persistent CIPN grading 2\u0026ndash;3 were randomly assigned into TCM (n\u0026thinsp;=\u0026thinsp;72), vitamin B1 (n\u0026thinsp;=\u0026thinsp;75) or warm water (n\u0026thinsp;=\u0026thinsp;80) group (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). At baseline, the three groups were generally well matched demographically and clinically, including prior neuropathy, tumor status and chemotherapy cycles (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). For TCM, vitamin B1 and warm water groups, more than half of patients underwent the first treatment line with PTX (50.0% vs 53.3% vs 51.3%); most of the patients received nab-PTX rather than docetaxel (94.4% vs 94.7% vs 96.3%); the proportion of patients receiving treatment other than chemotherapy was 52.8%, 53.3% and 52.5%. In TCM group, 76.4% patients reported CIPN after the first cycle of PTX chemotherapy, and 8.3% patients reported CIPN after the third cycle, which was similar with the other two groups. Analysis by RECIST criteria for tumor status showed similar results of overall response rates (37.5% vs 36.0% vs 35.0%) and disease control rates (90.3% vs 89.3% vs 91.2%).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline demographics and clinical characteristics of the evaluable population\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDemographic and clinical characteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTCM(n\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eVitamin B1(n\u0026thinsp;=\u0026thinsp;75)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWarm water(n\u0026thinsp;=\u0026thinsp;80)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.83\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e61(84.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e63(84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e65(81.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11(15.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12(16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15(18.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years old)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60.89\u0026thinsp;\u0026plusmn;\u0026thinsp;9.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60.72\u0026thinsp;\u0026plusmn;\u0026thinsp;9.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.894\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.913\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;18.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(2.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1(1.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e18.5\u0026thinsp;~\u0026thinsp;23.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39(54.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39(52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e40(50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;24.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31(43.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34(45.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e39(48.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.946\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e68(94.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e70(93.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e74(92.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4(5.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5(6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6(7.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrior neuropathy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.862\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e67(93.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e68(90.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e73(91.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5(6.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7(9.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7(8.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistology\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.988\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdenocarcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22(30.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22(29.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e25(31.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSquamous cell carcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34(47.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36(48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e39(48.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeuroendocrine carcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11(15.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12(16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13(16.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5(6.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5(6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3(3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer stage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.916\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅢ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13(18.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15(20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14(17.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅣ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e59(81.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60(80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e66(82.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor status\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.989\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProgression disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7(9.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8(10.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7(8.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStable disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38(52.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40(53.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e45(56.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePartial response\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27(37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27(36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28(35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eECOG performance score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.962\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(4.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5(6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34(47.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35(46.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e39(48.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35(48.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37(49.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e36(45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment lines\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.996\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36(50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40(53.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e41(51.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25(34.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24(32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28(35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9(12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8(10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(2.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3(3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChemotherapy cycles\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.664\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5(6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e70(97.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e72(96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e75(93.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTypes of paclitaxel\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003enab-PTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e68(94.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e71(94.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e77(96.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.861\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDocetaxel\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4(5.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4(5.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3(3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatinum\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.696\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18(25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15(20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16(20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54(75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60(80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e64(80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eImmunotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.943\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44(61.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47(62.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e48(60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28(38.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28(37.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e32(40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntiangiogenic drugs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.821\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62(86.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e63(84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e70(87.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10(13.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12(16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10(12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: TCM, traditional Chinese medicine; ECOG, Eastern Cooperative Oncology Group; BMI, body mass index; nab-PTX, nanoparticle albumin-bound paclitaxel\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eAssessment of the Severity of CIPN\u003c/h3\u003e\n\u003cp\u003eThe severity of CIPN for TCM group had no significant difference compared to the other two groups at baseline (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The incidence of CIPN grading 2\u0026ndash;3 after two cycles of intervention were significantly lower in TCM group than in vitamin B1 and warm water groups (SPN: 90.3% vs 100.0% vs 100.0%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; MPN: 93.1% vs 100.0% vs 100.0%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). After four cycles of TCM therapy, the proportion of participants with SPN grading 2\u0026ndash;3 dropped to 83.3% (60/72) and MPN grading 2\u0026ndash;3 dropped to 73.6% (53/72), resulting in more significant distinction between treatment groups with the increasing of intervention cycles (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The Kaplan-Meier analysis indicated that the likelihood of CIPN relief compared was significantly higher in TCM group (48.6%) than in vitamin B1 (12%) and warm water group (7.5%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean time from study entry to first CIPN relief was 9.7, 11.6 and 11.8 weeks for TCM, vitamin B1 and warm water groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). A multivariable model analysis of CIPN relief correlates found that TCM therapy significantly increased the incidence of CIPN relief (OR\u0026thinsp;=\u0026thinsp;14.76; 95% CI, 5.39\u0026ndash;40.4, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), while negative factors were progression disease (OR\u0026thinsp;=\u0026thinsp;0.13; 95% CI, 0.03\u0026ndash;0.68; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016), stable disease (OR\u0026thinsp;=\u0026thinsp;0.331; 95% CI, 0.15\u0026ndash;0.72; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005) and antiangiogenic drugs (OR\u0026thinsp;=\u0026thinsp;0.23; 95% CI, 0.06\u0026ndash;0.88, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032) (Supplementary table 6\u0026ndash;7). Further, in a Cox regression analysis to control for CIPN relief time, TCM therapy (HR\u0026thinsp;=\u0026thinsp;9.76; 95% CI, 4.09\u0026ndash;23.31; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), progression disease (HR\u0026thinsp;=\u0026thinsp;0.17; 95% CI, 0.04\u0026ndash;0.74; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018) and stable disease (HR\u0026thinsp;=\u0026thinsp;0.46; 95% CI, 0.26\u0026ndash;0.82; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008) remained to be significant variables influencing CIPN relief (Supplementary table 8).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of CIPN severity grading and variable CIPN-related scales level between treatment groups within four cycles of intervention\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade/scales\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTCM\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eVitamin B1(n\u0026thinsp;=\u0026thinsp;75)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eWarm water(n\u0026thinsp;=\u0026thinsp;80)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003eGrade of SPN\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.793\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64(88.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e66(88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e73(91.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8(11.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9(12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7(8.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eCycle 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.226\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66(91.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e66(88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e71(88.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4(5.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9(12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9(11.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eCycle 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7(9.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65(90.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e67(89.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e69(86.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8(10.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e11(13.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eCycle 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10(13.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62(86.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e67(89.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e67(83.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8(10.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13(16.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eCycle 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12(16.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60(83.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e64(85.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e63(78.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11(14.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e17(21.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGrade of MPN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.732\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50(69.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e50(66.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e58(72.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22(30.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e25(33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e22(27.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eCycle 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(1.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66(91.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e52(69.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e57(71.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5(6.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23(30.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23(28.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eCycle 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5(6.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e67(93.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e56(74.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e52(65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19(25.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e28(35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eCycle 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12(16.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60(83.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e52(69.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e50(62.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23(30.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e30(37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eCycle 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19(26.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53(73.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e48(64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e49(61.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27(36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e31(38.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCIPN-related outcomes\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFACT/GOG-Ntx\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.69\u0026thinsp;\u0026plusmn;\u0026thinsp;4.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.51\u0026thinsp;\u0026plusmn;\u0026thinsp;3.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16.55\u0026thinsp;\u0026plusmn;\u0026thinsp;4.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.183\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNPS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23.78\u0026thinsp;\u0026plusmn;\u0026thinsp;7.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e22.93\u0026thinsp;\u0026plusmn;\u0026thinsp;8.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.734\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eQoL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37.17\u0026thinsp;\u0026plusmn;\u0026thinsp;5.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e37.65\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e37.56\u0026thinsp;\u0026plusmn;\u0026thinsp;3.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.805\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eCycle 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFACT/GOG-Ntx\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.56\u0026thinsp;\u0026plusmn;\u0026thinsp;3.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16.15\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16.48\u0026thinsp;\u0026plusmn;\u0026thinsp;5.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.017\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNPS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23.4\u0026thinsp;\u0026plusmn;\u0026thinsp;7.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23.38\u0026thinsp;\u0026plusmn;\u0026thinsp;8.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.009\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eQoL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39.13\u0026thinsp;\u0026plusmn;\u0026thinsp;5.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e38.52\u0026thinsp;\u0026plusmn;\u0026thinsp;4.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e37.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.114\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eCycle 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFACT/GOG-Ntx\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.01\u0026thinsp;\u0026plusmn;\u0026thinsp;4.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17.87\u0026thinsp;\u0026plusmn;\u0026thinsp;4.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e18.19\u0026thinsp;\u0026plusmn;\u0026thinsp;5.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNPS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18.69\u0026thinsp;\u0026plusmn;\u0026thinsp;6.55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24.04\u0026thinsp;\u0026plusmn;\u0026thinsp;6.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e25.23\u0026thinsp;\u0026plusmn;\u0026thinsp;8.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eQoL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40.71\u0026thinsp;\u0026plusmn;\u0026thinsp;5.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e38.31\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e37.14\u0026thinsp;\u0026plusmn;\u0026thinsp;3.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eCycle 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFACT/GOG-Ntx\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.03\u0026thinsp;\u0026plusmn;\u0026thinsp;3.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19.01\u0026thinsp;\u0026plusmn;\u0026thinsp;3.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e20.06\u0026thinsp;\u0026plusmn;\u0026thinsp;4.88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNPS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17.49\u0026thinsp;\u0026plusmn;\u0026thinsp;6.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26.03\u0026thinsp;\u0026plusmn;\u0026thinsp;6.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e26.73\u0026thinsp;\u0026plusmn;\u0026thinsp;8.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eQoL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42.03\u0026thinsp;\u0026plusmn;\u0026thinsp;5.82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e36.85\u0026thinsp;\u0026plusmn;\u0026thinsp;4.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e35.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eCycle 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFACT/GOG-Ntx\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20.43\u0026thinsp;\u0026plusmn;\u0026thinsp;3.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e22.41\u0026thinsp;\u0026plusmn;\u0026thinsp;6.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNPS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.75\u0026thinsp;\u0026plusmn;\u0026thinsp;5.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27.71\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e29.24\u0026thinsp;\u0026plusmn;\u0026thinsp;9.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eQoL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e36.04\u0026thinsp;\u0026plusmn;\u0026thinsp;4.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e33.56\u0026thinsp;\u0026plusmn;\u0026thinsp;4.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: CIPN, chemotherapy-induced peripheral neuropathy; TCM, traditional Chinese medicine; SPN, sensory peripheral neuropathy; MPN, motor peripheral neuropathy; FACT/GOG-Ntx, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity; NPS, Neuropathy Pain Scale; QoL, Quality of Life\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eEfficacy outcomes of TCM intervention in CIPN relief and paclitaxel dose reductions/cessation compared to vitamin B1 and warm water\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOutcome of paclitaxel\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTCM(n\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eVitamin B1(n\u0026thinsp;=\u0026thinsp;75)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWarm water(n\u0026thinsp;=\u0026thinsp;80)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCIPN relief\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37(51.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66(88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e74(92.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35(48.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9(12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6(7.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRelief time (weeks)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.72\u0026thinsp;\u0026plusmn;\u0026thinsp;2.83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDose reductions/cessation of paclitaxel\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e61(84.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53(70.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e46(57.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11(15.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22(29.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34(42.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime of dose reductions/cessation (weeks)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11.08\u0026thinsp;\u0026plusmn;\u0026thinsp;2.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.62\u0026thinsp;\u0026plusmn;\u0026thinsp;2.86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.66\u0026thinsp;\u0026plusmn;\u0026thinsp;3.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.011\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDose reductions/cessation cycles\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e61(84.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53(70.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e46(57.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(1.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5(6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(1.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5(6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(1.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7(9.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17(21.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9(12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12(15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOutcomes of nab-PTX\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eTCM(n\u0026thinsp;=\u0026thinsp;68)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eVitamin B1 (n\u0026thinsp;=\u0026thinsp;71)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eWarm water (n\u0026thinsp;=\u0026thinsp;77)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eP\u003c/b\u003e \u003cb\u003evalue\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCumulative dose of nab-PTX (mg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1528.87\u0026thinsp;\u0026plusmn;\u0026thinsp;81.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1490.97\u0026thinsp;\u0026plusmn;\u0026thinsp;124.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1459.45\u0026thinsp;\u0026plusmn;\u0026thinsp;134.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRelative dose intensity of nab-PTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: CIPN, chemotherapy-induced peripheral neuropathy; TCM, traditional Chinese medicine; nab-PTX, nanoparticle albumin-bound paclitaxel\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003eEvaluation of CIPN-related Symptoms and QoL\u003c/h3\u003e\n\u003cp\u003ePatient-reported neurological assessment outcomes evaluated by FACT/GOG-Ntx, NPS and QoL scales showed similar neuropathic burden between treatment groups at baseline (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). FACT/GOG-Ntx decreased from 16.7 at baseline to 11.5 after four cycles of TCM therapy, with NPS reduced from 23.8 at baseline to 16.8. There were 45.8% (33/72) and 56.9% (41/72) of patients who had at least a 30% reduction in FACT/GOG-Ntx and NPS from baseline to the end of intervention, considered responsive to TCM therapy. However, these two scales remained increasing in the other two groups, resulting in significant differences between treatment groups after four cycles of intervention (FACT/GOG-Ntx: 11.5 vs 20.4 vs 22.4, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; NPS: 16.8 vs 27.7 vs 29.2, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was no significant difference in the mean QoL score at baseline for TCM, vitamin B1 and warm water groups (37.2 vs 37.7 vs 37.6, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.805). QoL score increased after four cycles of TCM therapy, indicating better physical and emotional well-being, while both vitamin B1 and warm water exhibited limited efficacy in improving patients\u0026rsquo; QoL (42.6 vs 36.0 vs 33.6, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e displayed the distinction of these scales between patient groups became more significant with the increasing of intervention cycles.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eAdverse Events Associated with TCM\u003c/h2\u003e\u003cp\u003eOur study showed one patient had transient mild skin itching after hands and feet immersion, but symptoms were relieved without TCM intervention. No severe adverse events associated with the Qufenghuoxue formula were reported, including skin eruption, bruising, and local persistent pain. One patient had papules on skin in vitamin B1 group, which were relieved with antiallergic treatment. No patients withdrew from the study due to intolerance.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eCumulative Dose of Paclitaxel\u003c/h2\u003e\u003cp\u003eThe rate of PTX dose reductions or cessation as a result of CIPN was lower in TCM group than in vitamin B1 and warm water groups (15.3% vs 29.3% vs 42.5%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Owing to the small number of patients receiving docetaxel, we focus on the cumulative dose of nab-PTX analyzed. The mean cumulative dose of nab-PTX was 1528.9 mg/m\u003csup\u003e2\u003c/sup\u003e, 1491.0 mg/m\u003csup\u003e2\u003c/sup\u003e and 1459.5 mg/m\u003csup\u003e2\u003c/sup\u003e in TCM, vitamin B1 and warm water groups, resulting in the significant difference of relative dose intensity of nab-PTX (0.98 vs 0.96 vs 0.94, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002). The Kaplan-Meier analysis showed that TCM group had higher likelihood of completing the recommended dose of nab-PTX (1560 mg/m\u0026sup2;) than the other two groups (83.8% vs 74.6% vs 59.7%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0034) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). In a Cox proportional hazards model, we estimated the hazard ratio (HR) of dose reductions or cessation due to CIPN (Supplementary table 9). With warm water as a reference, the univariate HR was 0.36 (95% CI, 0.18\u0026ndash;0.72; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004) for TCM and 0.59 (95% CI, 0.33\u0026ndash;1.05; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.074) for vitamin B1. The multivariate HR, adjusted for age and tumor status, was 0.34 (95% CI: 0.17\u0026ndash;0.67, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) and 0.56 (95% CI: 0.31\u0026ndash;1.00, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.053).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eFactors Associated with CIPN-related Outcomes\u003c/h2\u003e\u003cp\u003eThe multivariable model found a significant association with FACT/GOG- Ntx (F\u0026thinsp;=\u0026thinsp;11.798; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.605) (Supplementary table 10). Factors associated with lower FACT/GOG-Ntx were the Qufenghuoxue formula therapy (β = -11.17; 95% CI, -12.63 to -9.72; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), vitamin B1 therapy (β = -2.25; 95% CI, -3.68 to -0.81; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), age (β\u0026thinsp;=\u0026thinsp;0.15; 95% CI, 0.07 to 0.23; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), partial response (β = -2.64; 95% CI, -4.91 to -0.38; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.022), and stable disease (β = \u0026minus;2.82; 95% CI, \u0026minus;\u0026thinsp;5.01 to \u0026minus;\u0026thinsp;0.62; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012). These factors above explained 60.5% of the total variance in FACT/GOG-Ntx. Multivariable analysis also identified the factors that were associated with NPS (F\u0026thinsp;=\u0026thinsp;8.044; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.511) and QoL (F\u0026thinsp;=\u0026thinsp;8.942; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.538). The independent variables included CIPN intervention, tumor histology and treatment lines. Patients who received TCM therapy were more inclined to have lower NPS (β = \u0026minus;12.57; 95% CI, \u0026minus;\u0026thinsp;14.77 to \u0026minus;\u0026thinsp;10.36; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and better QoL (β\u0026thinsp;=\u0026thinsp;9.11; 95% CI, 7.64 to 10.58; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Patients with the 2nd treatment line had similar results in terms of NPS (β = \u0026minus;11.39; 95% CI, \u0026minus;\u0026thinsp;17.20 to \u0026minus;\u0026thinsp;5.58; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and QoL scale (β\u0026thinsp;=\u0026thinsp;8.61; 95% CI, 4.75 to 12.48; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eCIPN is one of the dose-limiting toxicity resulting in chemotherapy dose reductions/cessation and impaired daily function. Hands and feet immersion with Qufenghuoxue formula could effectively relieve CIPN-related symptoms evaluated by FACT/GOG-Ntx and NPS scales, which might increase the likelihood of CIPN relief and improve quality of life. This strategy also increased the potential of completing the recommended nab-PTX dose with fewer dose modifications. We have established that it is a safe and feasible adjunctive treatment for advanced lung cancer patients developing moderate-to- severe CIPN.\u003c/p\u003e\u003cp\u003eAs PTX cumulative dose increased, CIPN-related symptoms worsened in the vitamin B1 and warm water groups, negatively impacting QoL. In contrast, Qufenghuoxue formula therapy significantly reduced FACT/GOG-NTx and NPS scores, indicating alleviated neuropathic symptoms. Our study indicated that Qufenghuoxue formula significantly reduced the incidence of CIPN grading 2\u0026ndash;3 compared to vitamin B1 and warm water, with effects becoming more pronounced over multiple cycles. It also shortened the mean time to CIPN relief, and increased the likelihood of CIPN relief by 48.6% after four intervention cycles, demonstrating its efficacy and safety. Patients with partial tumor response benefited more from Qufenghuoxue formula than those with stable or progressive disease. It might be due to lower tumor burden and better overall health, qualifying patients to deal with adverse effects of chemotherapy with sufficient function of vital organs. Regression analysis confirmed its significant therapeutic benefits, with partial tumor response correlating with CIPN relief. This result was also consistent with the multivariable analysis of positive correlates promoting CIPN relief. Post-treatment follow-up is needed to determine if Qufenghuoxue formula provides long-term benefit for CIPN relief.\u003c/p\u003e\u003cp\u003ePrevious research suggested that vitamin B1 might protect patients against the onset and development of CIPN through preventing nerve dysfunction and nerve damage\u003csup\u003e\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Patients receiving vitamin B1 during chemotherapy had a lower CIPN rate after one month treatment than those without vitamin B1 (42.9% vs 63.8%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003csup\u003e18\u003c/sup\u003e. An explanation for limited efficacy in our vitamin B1 group might be the short trial duration of intervention or insufficient symptom improvement to affect CIPN severity grading. Longer follow-up is necessary to assess its potential benefits on subjective symptoms and objective responses that require reversal of neuropathy process. Notably, the efficacy of assessment scales varied in clinical trials, which may be a result of discrepancies between clinician- and patient-reported outcomes with minimal agreement and variation by CIPN grade\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Our patient-reported outcome measures reflect a real-world setting of advanced lung cancer patients.\u003c/p\u003e\u003cp\u003ePTX dose reductions or complete cessation is implemented among patients with CIPN-related symptoms\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Both dose reductions and treatment cessation due to CIPN negatively impact survival, considerably\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. We took the cumulative nab-PTX dose as a secondary endpoint to reflect its significant influence on treatment outcomes. 83.8% of patients receiving Qufenghuoxue formula in our study completed the recommended nab-PTX dose, compared to 74.6% and 59.7% in vitamin B1 and warm water groups. The effects of Qufenghuoxue formula on cancer treatment showed that it increased the likelihood of completing recommended nab-PTX doses, leading to higher cumulative doses and relative dose intensity. Cox regression further confirmed the reduced risk of dose reductions/cessation. Sato et al. reported that cooling group had lower incidence of moderate-to-high CIPN than control group without affecting paclitaxel dose reductions in cancer patients\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Differences in treatment regimens, histology, chemotherapy cycles and cumulative doses might explain the discrepancy. As a new paclitaxel drug encapsulated with liposomes, nab-PTX can improve bioavailability and reduce toxicities such as myelosuppression due to lower bio-disposition in vital organs\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. However, a recent study showed that nab-PTX was associated with more severe CIPN than traditional taxanes\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Thus, strategies such as Qufenghuoxue formula to manage CIPN and maintain optimal nab-PTX dosing level are of critical clinical importance.\u003c/p\u003e\u003cp\u003eNo pharmacologic agent could conclusively prevent CIPN in over 40 randomized trials involving anticonvulsants, antidepressants, vitamins and minerals\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Paclitaxel causes microtubule disruption in peripheral nerves, further impairing axonal transport, altering homeostasis and triggering CIPN\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. CIPN is ascribed to \u0026ldquo;blockage syndrome\u0026rdquo; or \u0026ldquo;Bi Zheng\u0026rdquo; in TCM theory\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Firstly, Qufenghuoxue formula therapy may enhance microcirculation and neurotransmitter transmission to relieve \u0026ldquo;blockage syndrome\u0026rdquo;. Secondly, it may stimulate meridian points on limb extremities through transdermal absorption in order to improve peripheral blood flow and alleviate sensory disturbance. Thirdly, Qufenghuoxue formula contains nine active compounds (e.g., Huangqi for nerve development and regeneration, Guizhi for dispersing blockage, Jixueteng for relieving blood stasis, Xixiancao for anti-inflammatory/antioxidant effect with anti-tumor activities). They collectively reduce blood viscosity, support nerve repair, and mitigate nerve damage. In contrast to oral or intravenous drugs, topical administration avoids potential toxicity of liver, kidney and gastrointestinal tract. Further research is needed to clarify its molecular mechanisms.\u003c/p\u003e\u003cp\u003eThis is the first prospective and randomized study to evaluate the efficacy and safety for TCM therapy in CIPN management among advanced lung cancer patients. Qufenghuoxue formula can relieve CIPN-related symptoms and enable optimal nab-PTX dosing. However, some limitations must be acknowledged. The observation period of 4\u0026ndash;6 chemotherapy cycles precludes assessment of long-term benefits of intervention. Long-term course with post-treatment period may determine whether Qufenghuoxue formula can reduce CIPN severity permanently and improve therapeutic outcomes. As multi-center analysis was interrupted by the outbreak of COVID-19 virus infection, originating from a single center might limit the generalizability of these results. Finally, we should further consider the effect of other potential confounding factors (e.g., nutritional or dietary supplements, patients\u0026rsquo; lifestyle) in multicenter validation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAs a medicine for external use, Qufenghuoxue formula therapy is demonstrated to be feasible and well-tolerated in advanced lung cancer patients with PTX-related peripheral neuropathy. This strategy reduces CIPN severity grading, accelerates symptom relief, and improves quality of life. It also has the potential to prevent dose-limiting events and be supportive for completing the recommended nab-PTX dosing. These promising results warrant further investigation into long-term benefits of this valuable candidate for CIPN management.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003enab-PTX, nanoparticle albumin-bound paclitaxel; TCM, traditional Chinese medicine; CIPN, chemotherapy-induced peripheral neuropathy; NCI-CTCAE, National Cancer Institute-Common Terminology Criteria for Adverse Events; FACT/GOG-Ntx, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity; NPS, Neuropathy Pain Scale; RECIST, Response Evaluation Criteria In Solid Tumors; QoL, Quality of Life; SPN, sensory peripheral neuropathy; MPN, motor peripheral neuropathy; ECOG, Eastern Cooperative Oncology Group; BMI, body mass index; IQR, interquartile range; OR, odds ratio; SD, standard deviation; HR, hazard ratio; CI, confidence interval.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the patients who have participated in this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure of competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Zhongshan Hospital, Fudan University (No. B2021-257R).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate and publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients signed informed consent regarding participating this trial and publishing their data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have read and approved the revised version submitted and published.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; agreed on the journal to which the article has been submitted; and agreed to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Science and Technology Commission of Shanghai Municipality (grant number: 20DZ2261200, 20DZ2254400); the Construction of Multidisciplinary Cooperative Diagnosis and Treatment for Severe Pneumonia (grant number: W2020-013); the Mechanisms of Antibiotic Resistance in Severe Pneumonia Treated with Traditional Chinese and Western Medicine (grant number: ZY (2021-2023)-0207-01); Shanghai Municipal Key Clinical Specialty (grant number: shslczdzk02201); National Natural Science Foundation of China (grant number: 82170110); Fujian Provincial Department of Science and Technology (grant number: 2022D014), Shanghai Pujiang Program (grant number: 20PJ1402400) and Quzhou Science and Technology Bureau Programme Project (grant number: 2023K112).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe raw data supporting the conclusions of this article will be made available from the corresponding authors under reasonable requests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSiegel RL, Miller KD, Wagle NS, et al. 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Association of Taxane Type With Patient-Reported Chemotherapy-Induced Peripheral Neuropathy Among Patients With Breast Cancer. \u003cem\u003eJAMA Netw Open\u003c/em\u003e 2022; 5: e2239788. \u003cdiv class=\"ExternalRefDOI\"\u003e2022/11/03\u003c/div\u003e. DOI: 10.1001/jamanetworkopen.2022.39788.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLoprinzi CL, Lacchetti C, Bleeker J, et al. Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update. \u003cem\u003eJ Clin Oncol\u003c/em\u003e 2020; 38: 3325\u0026ndash;3348. \u003cdiv class=\"ExternalRefDOI\"\u003e2020/07/15\u003c/div\u003e. DOI: 10.1200/jco.20.01399.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVerweij J, Clavel M and Chevalier B. Paclitaxel (Taxol) and docetaxel (Taxotere): not simply two of a kind. \u003cem\u003eAnn Oncol\u003c/em\u003e 1994; 5: 495\u0026ndash;505. 1994/07/01. DOI: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/oxfordjournals.annonc.a058903\u003c/span\u003e\u003cspan address=\"10.1093/oxfordjournals.annonc.a058903\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Paclitaxel, chemotherapy-induced peripheral neuropathy, advanced lung cancer, traditional Chinese medicine, recommended chemotherapy dose, randomized clinical trial","lastPublishedDoi":"10.21203/rs.3.rs-6802916/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6802916/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eTo assess the benefits of hands and feet immersion with traditional Chinese medicine (TCM) Qufenghuoxue formula on chemotherapy-induced peripheral neuropathy (CIPN) in advanced lung cancer patients receiving paclitaxel.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eIn this prospective trial, 227 patients with CIPN grading 2\u0026ndash;3 randomly received TCM therapy, oral vitamin B1 or warm water immersion during paclitaxel chemotherapy. Assessment measures such as Neuropathy Pain Scale (NPS), and the potential of completing recommended paclitaxel dosing were used to evaluate the efficacy.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe incidence of sensory peripheral neuropathy and motor peripheral neuropathy with NCI-CTCAE grading 2\u0026ndash;3 dropped to 83.3% and 73.6% in TCM group, significantly lower than vitamin B1 and warm water groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). TCM therapy improved FACT/GOG-Ntx (11.5 vs 20.4 vs 22.4), NPS (16.8 vs 27.7 vs 29.2) and Quality of Life scales (42.6 vs 36.0 vs 33.6) (all P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Compared to vitamin B1 and warm water groups, more patients in TCM group experienced CIPN relief (48.6% vs 12.0% vs 7.5%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) with decreased mean time to CIPN relief. TCM group also had greater potential of completing recommended dose level of paclitaxel (83.8% vs 74.6% vs 59.7%, P\u0026thinsp;=\u0026thinsp;0.0034). With warm water as a reference, the multivariate hazard ratio of paclitaxel dose reductions/cessation as a result of CIPN was 0.34 for TCM and 0.56 for vitamin B1.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eQufenghuoxue formula was a feasible strategy in relieving CIPN-related symptoms, reducing CIPN severity grading, and improving the potential of completing recommended paclitaxel dosing in advanced lung cancer patients.\u003c/p\u003e\u003ch2\u003eTrial Registration\u003c/h2\u003e\u003cp\u003eChinese Clinical Trial Registry No. ChiCTR2300069949. Registered 30 March 2023, URL www.chictr.org/cn/.\u003c/p\u003e","manuscriptTitle":"The Efficacy and Safety of Traditional Chinese Medicine Qufenghuoxue Formula on Peripheral Neuropathy Induced by Paclitaxel in Advanced Lung Cancer：A Randomized Clinical Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-18 13:04:28","doi":"10.21203/rs.3.rs-6802916/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-20T05:26:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-16T23:04:08+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-29T07:54:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"126376666153196307476194251070290319486","date":"2025-09-25T13:15:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"167304906028340480102095466114967052266","date":"2025-09-25T10:56:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"152401947998763311641973805376105251955","date":"2025-07-17T13:39:35+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-13T20:14:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-08T13:29:10+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-05T06:42:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"Supportive Care in Cancer","date":"2025-06-02T13:53:38+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"106a59f0-41be-4d0f-b5a6-979bd951e16b","owner":[],"postedDate":"July 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-29T16:01:16+00:00","versionOfRecord":{"articleIdentity":"rs-6802916","link":"https://doi.org/10.1007/s00520-025-10273-7","journal":{"identity":"supportive-care-in-cancer","isVorOnly":false,"title":"Supportive Care in Cancer"},"publishedOn":"2025-12-22 15:57:46","publishedOnDateReadable":"December 22nd, 2025"},"versionCreatedAt":"2025-07-18 13:04:28","video":"","vorDoi":"10.1007/s00520-025-10273-7","vorDoiUrl":"https://doi.org/10.1007/s00520-025-10273-7","workflowStages":[]},"version":"v1","identity":"rs-6802916","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6802916","identity":"rs-6802916","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}