Preventive effect of combined compression and cooling therapy on chemotherapy-induced peripheral neuropathy in taxane-based chemotherapy for lung cancer

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However, they can induce chemotherapy-induced peripheral neuropathy (CIPN), which often has a significant impact on quality of life. Currently, only duloxetine is recommended for the relief of CIPN pain, but it does not provide significant improvement and it is important to prevent the onset of CIPN. There are few reports of preventive effects on chemotherapy for lung cancer and little is known about the combination of compression and cooling therapies. Methods At our institution, we have conducted a study in patients with advanced lung cancer on a taxane-containing regimen, using a combination of compression therapy and cooling therapy, to determine the preventive effect on CIPN. Results The results showed a reduction in the incidence of CIPN in the group treated with combination therapy compared with previous reports, while ensuring safety. Conclusion We believe that the combination of compression and cooling therapy may be useful in the prevention of CIPN. Chemotherapy-induced peripheral neuropathy (CIPN) Compression therapy Cooling therapy Taxane Figures Figure 1 Figure 2 Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a well-known side effect of taxane-based cytotoxic anticancer drugs, reported by Seretny to occur in approximately 60% of patients [ 1 ]. CIPN presents a wide range of symptoms and severity and can have a significant impact on quality of life [ 2 , 3 ]. CIPN is caused by neurotoxic effects on neurons, and sensory symptoms tend to be more intense than motor or autonomic symptoms. Damage to dorsal root ganglion neurons and their axons can cause terminal pain and dysesthesia as well as other symptoms such as dysesthesia, dysalgesia, and hyperalgesia. In general, CIPN occurs in a dose-dependent manner, with symptoms usually beginning during the first two months of treatment, progressing during the continuation of chemotherapy, and stabilizing after completion of treatment [ 4 ]. Among them, taxanes are associated with mixed polyneuropathy, mainly with abnormal limb paresthesia, which correlates with a single dose and total dose [ 5 ]. On the other hand, weekly regimens are reported to cause more severe peripheral neuropathy than tri-weekly regimens, and the number of doses and frequency over a period of time may be involved [ 6 ]. Neuropathic pain is sometimes associated with neuropathic pain, and as the disease progresses, it also causes autonomic neuropathy, including distal extremity-dominant burning sensation, total sensory disturbance, sensory motor impairment, and bradyarrhythmia [ 7 – 9 ]. Currently, the American Society of Clinical Oncology (ASCO) guidelines recommend duloxetine as the only drug therapy for pain in CIPN [ 10 ]. However, duloxetine is more effective than taxane-based cytotoxic agents in patients with platinum-induced disease [ 11 ], and taxane-based cytotoxic agents have been shown to be more effective than taxanes. There are currently no drugs that are effective against CIPN caused by taxane-based cytotoxic agents. Therefore, it is important to prevent CIPN from occurring. Currently, exercise therapy [ 10 ] and cooling therapy [ 12 ] are recommended as preventive measures. Cooling therapy is a prophylactic measure to reduce exposure by cooling during the time of highest drug blood concentration, which causes vasoconstriction, thereby decreasing blood circulation and the amount of anticancer drug delivered. Compression therapy, which lowers epidermal temperature by 1 to 2℃ [ 13 , 14 ], may also prevent CIPN. However, there are no data showing that the combination of cooling and compression therapy is effective in preventing CIPN, so we examined the usefulness and safety of this therapy. Patients and Methods Statement of Ethics The Institutional Ethics Review Boards of St. Franciscan Himeji St. Mary's Hospital (S023-012) and Hyogo Medical University (No.4507) both approved this study on August 23, 2023, and September 19, 2023, respectively, in compliance with the 2013 Declaration of Helsinki.The requirement for informed consent was waived owing to the study’s retrospective nature. The study was a single-centre, backward-looking observational study. Between April 2021 and 31 March 2023, patients with advanced lung cancer on a regimen including taxane-based anticancer drugs at our hospital were asked, according to a measurement chart (Fig. 1 ), to wear two surgical gloves on each hand from 30 minutes before administration of taxane-based anticancer drugs until 30 minutes after completion of administration. Surgical gloves (Toray Medical, Inc./Surgical gloves: Sensiderm non-powder) (Fig. 2 ) were worn on each hand, and elastic stockings (Terumo, Inc./Jobst) (Fig. 2 ) were worn on both lower limbs, based on the measurement chart (Fig. 1 ), and compression therapy was performed using cooling gloves (cooling agent inserted in a fabric glove pocket and placed in another glove pocket) on both hands. The 53 patients were treated with a combination of compression therapy wearing a cooling glove (a cooling agent is inserted into a fabric glove pocket and both hands are inserted into a pocket in another glove) (Fig. 2 ) on both hands. Peripheral neuropathy was assessed by the physician at the time of each chemotherapy administration using the Common Terminology Criteria for Adverse Evevts (CTCAE) v5.0. Patients with a history of neuropathy, peripheral oedema or an underlying condition that precluded compression or cooling therapy were excluded. The study was approved by the Ethical Review Committee for Clinical Research at Himeji St Mary's Hospital in accordance with the ethical guidelines for medical research involving human subjects (approval number: S023-012). Results A table of the patient background of our study is presented (Table 1 ). Treatment regimens included the IMPOWER 150 (carboplatin + paclitaxel + bevacizumab + atezolizumab) regimen in 13 patients, the IMPOWER 130 (carboplatin + nab-paclitaxel + atezolizumab) regimen in 6 patients, the KEYNOTE 407 (carboplatin + nab-paclitaxel + pembrolizumab) regimen in 4 patients, carboplatin + paclitaxel + bevacizumab regimen in 2 patients, carboplatin + paclitaxel (with radiotherapy) regimen in 6 patients, carboplatin + nab-paclitaxel regimen in 7 patients, nab-paclitaxel alone regimen in 3 cases, docetaxel + Cyramza regimen in 8 cases and docetaxel monotherapy regimen in 4 cases, with immunotherapy combination regimens accounting for 43% and angiogenesis inhibitor combination regimens for 43%. The median age is characterised by a relatively elderly population. This is due to the location of the hospital and the fact that in recent years, with regard to the initial dose in Japan, it has been possible to start dosing with at least a one-step reduction of each drug. Of note, 0% of patients required dose reduction during chemotherapy administration, and the CTCAE v5.0 grades for the various regimens were very good, with a median grade of 0-0.5. Table 1 Regimen, number of patients, age (median), number of administration courses (median), initial induction dose (median), reduction rate, CIPN grade (median) in this study regimen n Age (Medium) Number of doses (medium) Induction dose (medium) Chemotherapy reduction rate percentage (medium) CIPN grade (medium) CBDCA + PAC + Bev + atezolizumab 13 73 (56–80) 6 (1–6) 100% 0% 0 (0–2) CBDCA + nab-PAC + atezolizumab 6 77 (73–83) 6 (1–6) 100% 0% 0 (0–1) CBDCA + nab-PAC + pembrolizumab 4 81.5 (74–87) 4 (3–4) 90% 0% 0 (0–0) CBDCA + PAC + Bev 2 71.5 (71–72) 4 (2–6) 90% 0% 0 (0–0) CBDCA + PAC(+ RT) 6 79 (62–88) 6 (4–6) 83% 0% 0 (0–0) CBDCA + nab-PAC 7 74 (61–81) 6 (1–6) 100% 0% 0 (0–2) nab-PAC 3 88 (86–89) 2 (1–4) 80% 0% 0 (0–2) DOC + RAM 8 77 (56–81) 5.5 (1–17) 80% 0% 0 (0–2) DOC 4 80.5 (73–83) 2 (1–6) 90% 0% 0.5 (0–1) The incidence of CIPN by course is shown next (Fig. 3 ), with CIPN starting to occur from the third course and no new cases of CIPN from the sixth course. A total of 11 patients developed the condition, with a proportion of 20.8%. No patient had CIPN of grade 3 or above in CTCAE v5.0. There were also 0% grade 3 or higher adverse events The incidence of CIPN for each of the taxane-based anticancer drugs is shown. Both paclitaxel and nab-paclitaxel caused the onset of CIPN from the third course, with 19.0% (4 of 21 patients) and 15.0% (3 of 20 patients) at the sixth course, respectively. Docetaxel began to show incidence from the third course, probably because it was used more frequently after the second line, with a final incidence of 33.3% (4 out of 12 patients). Adverse events in pressure cooling therapy are shown (Fig. 4 ). Skin pain and redness occurred in 18.9%, numbness and tingling in 15.1%, frostbite and blistering in 1.9% each. No life-threatening adverse events were observed. Discussion There are no established diagnostic criteria for CIPN, and the diagnosis is based on the history of use of neuropathy-inducing anticancer drugs, the time of appearance of peripheral neuropathy and clinical symptoms. CIPN is symptomatically classified into sensory neuropathy, motor neuropathy and autonomic neuropathy. Among these, the subjective symptoms of sensory neuropathy are described as numbness, paresthesia, tingling or tingling sensation, twitching and pain. Symptoms are particularly prevalent in the peripheral limbs, and are referred to as the glove and sticking type [ 15 ]. The symptoms are usually mixed, and the same symptom is often reported as different symptoms in the patient's phenotype. With regard to pain in particular, it is important to exclude other somatosensory system lesions or diseases, as the pain is caused by the causative anticancer drug. Pathological classifications include axonopathy, neuronopathy and myelinopathy. Axonopathy in particular is the most common form of CIPN, caused by vinca alkaloids and taxanes, and presents with glove-and-stocking type sensory deficits beginning at the extremity ends. A well-known risk factor for the development of CIPN is diabetes mellitus [ 16 , 17 ], and in a study of risk factors in patients undergoing taxane and platinum chemotherapy, older age and number of chemotherapy cycles were identified as risk factors [ 18 ]. It has also been reported that patients with lower haemoglobin, higher BMI and older age are at higher risk of developing CIPN with paclitaxel or oxaliplatin [ 19 ]. The assessment of CIPN is divided into quantitative and questionnaire assessments, with quantitative assessments including sensory function assessment, motor function assessment and electrophysiology tests, each of which can assess which senses are impaired and to what extent. Questionnaire assessments can be divided into medical and patient-reported assessments. The Common Terminology Criteria for Adverse Evetnts (CTCAE) is used as a tool for assessment by healthcare professionals. This was also used in this study and is a tool that can be used easily, but it is difficult to judge the boundaries. However, it is difficult to judge the boundaries of the method, and it is easy to reflect the discretion of the healthcare provider compared to the patient's subjective symptoms, and discrepancies have been pointed out [ 20 ]. Patient-reported assessment tools include the Europian Organisation for Reserch and Treatment of Cancer Quality of life Questionnaire-CIPN tenty-item scale (QLQ-CIPN20) and the CIPN20, Functional Assessment of Cancer Thepapy/Gynecologic Oncology Group-neurotoxicity (FACT-Ntx), which are recommended for use in clinical trials [ 21 ]. The most clinically useful assessment method is said to be patient-reported [ 22 ]. Regarding dose reduction or discontinuation of taxanes and other anticancer drugs in CIPN, prolonged dosing, dose reduction or discontinuation is important in management as there is no amental cure, and is recommended in the ASCO guidelines [ 10 ]. However, there have been no reports of discontinuation of anticancer drugs alone without loss of efficacy, so it is important to make decisions on a patient-by-patient basis, but if CIPN can be prevented, the drug should not be reduced or discontinued, and efficacy can be expected, which led us to conduct this study. Pregabalin, Gosyajinkigan and acetyl-L-carnitine are the pharmacological treatments with data for the prevention of CIPN. Pregabalin was evaluated for prophylaxis in breast cancer patients scheduled to receive paclitaxel using the EOTEC-QLQ20 and CTCAE v4.0, with no significant differences in prophylaxis [ 23 ]. There were two meta-analysis analyses of gosyajinkigan, neither of which sought significant differences in the incidence of CTCAE grade 2 or above [ 24 , 25 ]. Two reports on acetyl-L-carnitine for taxanes reported a significant exacerbation of CIPN symptoms in the treated group [ 26 , 27 ]. In general, pharmacotherapy was not effective in prevention. Non-pharmacological treatments include exercise therapy, with Müller et al. reporting a significant difference in CIPN symptoms in intervention groups with exercise therapy adherence exceeding 2/3 [ 28 ]. However, there are no definitive reports on the intensity, frequency, type or duration of exercise, and further evidence on exercise methods is needed. Further evidence needs to be accumulated. The cooling therapy is a strategy to reduce the incidence of CIPN by cooling the extremities during the administration of anticancer drugs to cause vasoconstriction, thereby decreasing the amount of circulating blood flow and, consequently, the amount of anticancer drugs that flow locally. Meta-analysis analyses have reported a predominant reduction in the frequency of CIPN with paclitaxel [ 12 ]. There have been no reports of serious side effects, but problems include the burden of administration on the healthcare provider and patient, and the preparation and storage of cooling equipment. In addition, cooling often causes discomfort and cannot be continued during administration. Compression therapy is a strategy to reduce the onset of CIPN by compressing the extremities during the administration of anticancer drugs to cause vasoconstriction, thereby reducing the amount of circulating blood flow and, consequently, the amount of anticancer drugs flowing locally. Compression may also have a protective effect on peripheral nerves by promoting venous and lymphatic return, thereby reducing the peripheral persistence of anticancer drugs [ 29 ]. In a study of patients treated with nab-paclitaxel by Tsuyuki et al, the frequency of grade 2 or higher CIPN was reduced [ 13 ], but no differences were found in patients treated with paclitaxel, which was studied by Kotani [ 30 ]. In addition, Kanbayashi et al. reported that there was no difference between the two groups in their comparison of compression and cooling therapy [ 14 ]. As with cooling therapy, problems include the burden on both providers and patients, in particular the difficulty of wearing two pairs of gloves, the difficulty of applying the gloves, and the difficulty of applying the gloves in a way that is not easy. The problems include the difficulty of application, especially when wearing two pairs of gloves, and the preparation, storage and reusability of the compression tools. In the present study, a combination of compression and cooling therapies was used in the hope of a complementary effect that could prevent the development of CIPN in a stable manner after discomfort and difficulty in continuation, suspension or withdrawal of both therapies, and to improve the prevention rate of CIPN. When patients eligible for chemotherapy were informed of the potential preventive effect, acceptance was good in most patients. The following problems and countermeasures were encountered during the implementation of this study in actual clinical practice: (1) cooling therapy was temporarily interrupted in some cases, but the surface temperature of the peripheral fingers was maintained by alternately placing the palms and back of the hands on the cooling material. (2) When it was difficult to put on two pairs of gloves, a device was devised to facilitate putting on gloves by applying Vaseline, baby powder or potato starch to the first pair of gloves. (3) Other doctors and healthcare professionals were not aware of compression therapy and cooling therapy, and education was essential. (4) The process from prior patient explanation, measurement and purchase of gloves and stockings to implementation was centralised and concise. The results of the study showed that CIPN was significantly reduced (paclitaxel: 43.80%/19.0%, nab-paclitaxel: 60.80%/15.0%) compared to previously reported results [ 31 ], with no patients experiencing Grade 3 or higher adverse events, and most side effects from the combination therapy were minor and did not need to be addressed. The study showed that the combination was safe and effective, as most of the side effects were minor and did not require treatment. There were no cases of dose reduction or discontinuation of chemotherapy, suggesting that the drugs can be effectively delivered to patients. This is the first study to look at the preventive effect of chemotherapy in lung cancer and the combined effect of compression therapy and cooling therapy. As a limitation of this study, there is no comparison with placebo and no comparison with compression therapy alone or cooling therapy alone, so the synergistic effect of the combined therapy is not truly known. The study was also based on medical assessments, and a patient-reported assessment tool would increase the accuracy of the study. Forward-looking, large-scale clinical trials with additional cases are needed. Declarations Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. The authors did not receive support from any organization for the submitted work. Author Contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Yasuhiro Nakajima. The first draft of the manuscript was written by Yasuhiro Nakajima and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Data availability: Details of the experiments are available within the article. In addition, documents related to this study have been uploaded to the website of Himeji St Mary's Hospital (Http://www.himemaria.or.jp). Compliance with Ethical Standards Disclosure of potential conflicts of interest: The authors have no relevant financial or non-financial interests to disclose. Research involving Human Participants and/or Animals: This study was performed in line with the principles of the Declaration of Helsinki. The study was approved by the Ethical Review Committee for Clinical Research at Himeji St Mary's Hospital in accordance with the ethical guidelines for medical research involving human subjects (approval number: S023-012,6/6/2023), retrospectively registered. Informed consent: The study was carried out with the verbal consent of the patients. Consent to publish: Not Applicable. Acknowledgements: Not applicable. References Seretny M, Currie GL, Sena ES et al (2014) Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. Pain 155:2461-2470. https://doi.org/10.1016/j.pain.2014.09.020 Simon NB, Danso MA, Alberico TA, Basch E, Bennett AV (2017) The prevalence and pattern of chemotherapy-induced peripheral neuropathy among women with breast cancer receiving care in a large community oncology practice. Qual Life Res 26:2763-2772. https://doi.org/10.1007/s11136-017-1635-0 Staff NP, Grisold A, Grisold W, Windebank AJ (2017) Chemotherapy-induced peripheral neuropathy: A current review. Ann Neurol 81:772-781. https://doi.org/10.1002/ana.24951 Pachman DR, Qin R, Seisler DK et al. 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BMC Cancer 21:548. https://doi.org/10.1186/s12885-021-08240-6 Pharmaceuticals and Medical Devices Agency. https//www.pmda.go.jp/PmdaSearch/iyakuSearch/. Accessed February 2024. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4337948","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":304218327,"identity":"f7876f5f-ee5e-44f7-b5c0-77534c3f42e9","order_by":0,"name":"Yasuhiro Nakajima","email":"","orcid":"","institution":"Society of St. Franciscan Himeji St. Mary's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yasuhiro","middleName":"","lastName":"Nakajima","suffix":""},{"id":304218328,"identity":"474b57b1-c393-4cc3-a753-c3fdca7711f2","order_by":1,"name":"Kozo Kuribayashi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIie3QPQrCMBiA4U+zCjpGhHqFr2Rw8DKVQrM0ILg4OHTSxQP0GN3ELRJolxygg4sI3Z0VsbaiTrFugnkhf8MDSQBsth+MlkMCgoP1mVQzNiHsO3JvkrwTY/1YHNR8uucb6st2Ph9DdyVhNjWQAeW401iIbRx4JNQcqPaAxQbi0AB2ESqR5OHoLJYKIAdgnQaEYx4iEVcFw09k8CBeTSIF+In010VF3EQX5VtS3nH1JDK+hWYBOUUXNcTMlyRcjB0nUykz/dirnlct5ZVaS9ZIQFc+t+TYjNhsNtufdAN6FkrMA1FUeAAAAABJRU5ErkJggg==","orcid":"","institution":"Hyogo College of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Kozo","middleName":"","lastName":"Kuribayashi","suffix":""},{"id":304218329,"identity":"3978ba76-fb65-4508-ae4f-017a4a0d04d2","order_by":2,"name":"Akio Tada","email":"","orcid":"","institution":"Society of St. Franciscan Himeji St. Mary's 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Medicine","correspondingAuthor":false,"prefix":"","firstName":"Toshiyuki","middleName":"","lastName":"Minami","suffix":""},{"id":304218333,"identity":"5b65941a-70b6-45df-b124-f5f8b0b2a19d","order_by":6,"name":"Arihiko Kanehiro","email":"","orcid":"","institution":"Society of St. Franciscan Himeji St. Mary's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Arihiko","middleName":"","lastName":"Kanehiro","suffix":""},{"id":304218334,"identity":"81024c8c-20e6-46d7-ad0e-2ac7feec8881","order_by":7,"name":"Takashi Kijima","email":"","orcid":"","institution":"Hyogo College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Takashi","middleName":"","lastName":"Kijima","suffix":""}],"badges":[],"createdAt":"2024-04-28 12:44:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4337948/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4337948/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57290285,"identity":"4b6ae2ee-bc22-4679-b85a-ff75328ebeeb","added_by":"auto","created_at":"2024-05-28 17:55:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":76317,"visible":true,"origin":"","legend":"\u003cp\u003eHow to measure hands and feet\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4337948/v1/8a947370b7deb81c2c9a8e98.png"},{"id":57290286,"identity":"2a4b446c-775c-418d-bdea-feaf54944a12","added_by":"auto","created_at":"2024-05-28 17:55:50","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":308087,"visible":true,"origin":"","legend":"\u003cp\u003eGloves/stockings in this study\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4337948/v1/68e36eea831697fecf83f7fd.png"},{"id":63299893,"identity":"6d8d2674-00c0-4936-bb14-b5bdf67d6af6","added_by":"auto","created_at":"2024-08-26 16:00:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":760542,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4337948/v1/dd9dd42e-0101-4998-ac1b-96cdeaa09d33.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Preventive effect of combined compression and cooling therapy on chemotherapy-induced peripheral neuropathy in taxane-based chemotherapy for lung cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChemotherapy-induced peripheral neuropathy (CIPN) is a well-known side effect of taxane-based cytotoxic anticancer drugs, reported by Seretny to occur in approximately 60% of patients [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. CIPN presents a wide range of symptoms and severity and can have a significant impact on quality of life [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. CIPN is caused by neurotoxic effects on neurons, and sensory symptoms tend to be more intense than motor or autonomic symptoms. Damage to dorsal root ganglion neurons and their axons can cause terminal pain and dysesthesia as well as other symptoms such as dysesthesia, dysalgesia, and hyperalgesia. In general, CIPN occurs in a dose-dependent manner, with symptoms usually beginning during the first two months of treatment, progressing during the continuation of chemotherapy, and stabilizing after completion of treatment [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Among them, taxanes are associated with mixed polyneuropathy, mainly with abnormal limb paresthesia, which correlates with a single dose and total dose [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. On the other hand, weekly regimens are reported to cause more severe peripheral neuropathy than tri-weekly regimens, and the number of doses and frequency over a period of time may be involved [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Neuropathic pain is sometimes associated with neuropathic pain, and as the disease progresses, it also causes autonomic neuropathy, including distal extremity-dominant burning sensation, total sensory disturbance, sensory motor impairment, and bradyarrhythmia [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCurrently, the American Society of Clinical Oncology (ASCO) guidelines recommend duloxetine as the only drug therapy for pain in CIPN [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, duloxetine is more effective than taxane-based cytotoxic agents in patients with platinum-induced disease [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and taxane-based cytotoxic agents have been shown to be more effective than taxanes. There are currently no drugs that are effective against CIPN caused by taxane-based cytotoxic agents. Therefore, it is important to prevent CIPN from occurring. Currently, exercise therapy [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and cooling therapy [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] are recommended as preventive measures. Cooling therapy is a prophylactic measure to reduce exposure by cooling during the time of highest drug blood concentration, which causes vasoconstriction, thereby decreasing blood circulation and the amount of anticancer drug delivered. Compression therapy, which lowers epidermal temperature by 1 to 2℃ [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], may also prevent CIPN. However, there are no data showing that the combination of cooling and compression therapy is effective in preventing CIPN, so we examined the usefulness and safety of this therapy.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cp\u003eStatement of Ethics\u003c/p\u003e \u003cp\u003e The Institutional Ethics Review Boards of St. Franciscan Himeji St. Mary's Hospital (S023-012) and Hyogo Medical University (No.4507) both approved this study on August 23, 2023, and September 19, 2023, respectively, in compliance with the 2013 Declaration of Helsinki.The requirement for informed consent was waived owing to the study\u0026rsquo;s retrospective nature.\u003c/p\u003e \u003cp\u003eThe study was a single-centre, backward-looking observational study. Between April 2021 and 31 March 2023, patients with advanced lung cancer on a regimen including taxane-based anticancer drugs at our hospital were asked, according to a measurement chart (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), to wear two surgical gloves on each hand from 30 minutes before administration of taxane-based anticancer drugs until 30 minutes after completion of administration. Surgical gloves (Toray Medical, Inc./Surgical gloves: Sensiderm non-powder) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) were worn on each hand, and elastic stockings (Terumo, Inc./Jobst) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) were worn on both lower limbs, based on the measurement chart (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), and compression therapy was performed using cooling gloves (cooling agent inserted in a fabric glove pocket and placed in another glove pocket) on both hands. The 53 patients were treated with a combination of compression therapy wearing a cooling glove (a cooling agent is inserted into a fabric glove pocket and both hands are inserted into a pocket in another glove) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) on both hands. Peripheral neuropathy was assessed by the physician at the time of each chemotherapy administration using the Common Terminology Criteria for Adverse Evevts (CTCAE) v5.0. Patients with a history of neuropathy, peripheral oedema or an underlying condition that precluded compression or cooling therapy were excluded. The study was approved by the Ethical Review Committee for Clinical Research at Himeji St Mary's Hospital in accordance with the ethical guidelines for medical research involving human subjects (approval number: S023-012).\u003c/p\u003e "},{"header":"Results","content":"\u003cp\u003eA table of the patient background of our study is presented (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Treatment regimens included the IMPOWER 150 (carboplatin\u0026thinsp;+\u0026thinsp;paclitaxel\u0026thinsp;+\u0026thinsp;bevacizumab\u0026thinsp;+\u0026thinsp;atezolizumab) regimen in 13 patients, the IMPOWER 130 (carboplatin\u0026thinsp;+\u0026thinsp;nab-paclitaxel\u0026thinsp;+\u0026thinsp;atezolizumab) regimen in 6 patients, the KEYNOTE 407 (carboplatin\u0026thinsp;+\u0026thinsp;nab-paclitaxel\u0026thinsp;+\u0026thinsp;pembrolizumab) regimen in 4 patients, carboplatin\u0026thinsp;+\u0026thinsp;paclitaxel\u0026thinsp;+\u0026thinsp;bevacizumab regimen in 2 patients, carboplatin\u0026thinsp;+\u0026thinsp;paclitaxel (with radiotherapy) regimen in 6 patients, carboplatin\u0026thinsp;+\u0026thinsp;nab-paclitaxel regimen in 7 patients, nab-paclitaxel alone regimen in 3 cases, docetaxel\u0026thinsp;+\u0026thinsp;Cyramza regimen in 8 cases and docetaxel monotherapy regimen in 4 cases, with immunotherapy combination regimens accounting for 43% and angiogenesis inhibitor combination regimens for 43%. The median age is characterised by a relatively elderly population. This is due to the location of the hospital and the fact that in recent years, with regard to the initial dose in Japan, it has been possible to start dosing with at least a one-step reduction of each drug. Of note, 0% of patients required dose reduction during chemotherapy administration, and the CTCAE v5.0 grades for the various regimens were very good, with a median grade of 0-0.5.\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\u003eRegimen, number of patients, age (median), number of administration courses (median), initial induction dose (median), reduction rate, CIPN grade (median) in this study\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eregimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge (Medium)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNumber of doses (medium)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInduction dose (medium)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eChemotherapy reduction rate percentage (medium)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCIPN grade (medium)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCBDCA\u0026thinsp;+\u0026thinsp;PAC\u0026thinsp;+\u0026thinsp;Bev\u0026thinsp;+\u0026thinsp;atezolizumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73 (56\u0026ndash;80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (1\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 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(4\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e83%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0\u0026ndash;0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCBDCA\u0026thinsp;+\u0026thinsp;nab-PAC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74 (61\u0026ndash;81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (1\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enab-PAC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88 (86\u0026ndash;89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e80%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDOC\u0026thinsp;+\u0026thinsp;RAM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77 (56\u0026ndash;81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.5 (1\u0026ndash;17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e80%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDOC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80.5 (73\u0026ndash;83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e90%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.5 (0\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe incidence of CIPN by course is shown next (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), with CIPN starting to occur from the third course and no new cases of CIPN from the sixth course. A total of 11 patients developed the condition, with a proportion of 20.8%. No patient had CIPN of grade 3 or above in CTCAE v5.0.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThere were also 0% grade 3 or higher adverse events\u003c/p\u003e \u003cp\u003eThe incidence of CIPN for each of the taxane-based anticancer drugs is shown. Both paclitaxel and nab-paclitaxel caused the onset of CIPN from the third course, with 19.0% (4 of 21 patients) and 15.0% (3 of 20 patients) at the sixth course, respectively. Docetaxel began to show incidence from the third course, probably because it was used more frequently after the second line, with a final incidence of 33.3% (4 out of 12 patients).\u003c/p\u003e \u003cp\u003eAdverse events in pressure cooling therapy are shown (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Skin pain and redness occurred in 18.9%, numbness and tingling in 15.1%, frostbite and blistering in 1.9% each. No life-threatening adverse events were observed.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThere are no established diagnostic criteria for CIPN, and the diagnosis is based on the history of use of neuropathy-inducing anticancer drugs, the time of appearance of peripheral neuropathy and clinical symptoms.\u003c/p\u003e \u003cp\u003eCIPN is symptomatically classified into sensory neuropathy, motor neuropathy and autonomic neuropathy. Among these, the subjective symptoms of sensory neuropathy are described as numbness, paresthesia, tingling or tingling sensation, twitching and pain. Symptoms are particularly prevalent in the peripheral limbs, and are referred to as the glove and sticking type [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The symptoms are usually mixed, and the same symptom is often reported as different symptoms in the patient's phenotype. With regard to pain in particular, it is important to exclude other somatosensory system lesions or diseases, as the pain is caused by the causative anticancer drug.\u003c/p\u003e \u003cp\u003ePathological classifications include axonopathy, neuronopathy and myelinopathy. Axonopathy in particular is the most common form of CIPN, caused by vinca alkaloids and taxanes, and presents with glove-and-stocking type sensory deficits beginning at the extremity ends.\u003c/p\u003e \u003cp\u003eA well-known risk factor for the development of CIPN is diabetes mellitus [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], and in a study of risk factors in patients undergoing taxane and platinum chemotherapy, older age and number of chemotherapy cycles were identified as risk factors [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. It has also been reported that patients with lower haemoglobin, higher BMI and older age are at higher risk of developing CIPN with paclitaxel or oxaliplatin [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe assessment of CIPN is divided into quantitative and questionnaire assessments, with quantitative assessments including sensory function assessment, motor function assessment and electrophysiology tests, each of which can assess which senses are impaired and to what extent. Questionnaire assessments can be divided into medical and patient-reported assessments. The Common Terminology Criteria for Adverse Evetnts (CTCAE) is used as a tool for assessment by healthcare professionals. This was also used in this study and is a tool that can be used easily, but it is difficult to judge the boundaries. However, it is difficult to judge the boundaries of the method, and it is easy to reflect the discretion of the healthcare provider compared to the patient's subjective symptoms, and discrepancies have been pointed out [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Patient-reported assessment tools include the Europian Organisation for Reserch and Treatment of Cancer Quality of life Questionnaire-CIPN tenty-item scale (QLQ-CIPN20) and the CIPN20, Functional Assessment of Cancer Thepapy/Gynecologic Oncology Group-neurotoxicity (FACT-Ntx), which are recommended for use in clinical trials [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The most clinically useful assessment method is said to be patient-reported [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRegarding dose reduction or discontinuation of taxanes and other anticancer drugs in CIPN, prolonged dosing, dose reduction or discontinuation is important in management as there is no amental cure, and is recommended in the ASCO guidelines [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, there have been no reports of discontinuation of anticancer drugs alone without loss of efficacy, so it is important to make decisions on a patient-by-patient basis, but if CIPN can be prevented, the drug should not be reduced or discontinued, and efficacy can be expected, which led us to conduct this study.\u003c/p\u003e \u003cp\u003ePregabalin, Gosyajinkigan and acetyl-L-carnitine are the pharmacological treatments with data for the prevention of CIPN. Pregabalin was evaluated for prophylaxis in breast cancer patients scheduled to receive paclitaxel using the EOTEC-QLQ20 and CTCAE v4.0, with no significant differences in prophylaxis [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. There were two meta-analysis analyses of gosyajinkigan, neither of which sought significant differences in the incidence of CTCAE grade 2 or above [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Two reports on acetyl-L-carnitine for taxanes reported a significant exacerbation of CIPN symptoms in the treated group [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In general, pharmacotherapy was not effective in prevention.\u003c/p\u003e \u003cp\u003eNon-pharmacological treatments include exercise therapy, with M\u0026uuml;ller et al. reporting a significant difference in CIPN symptoms in intervention groups with exercise therapy adherence exceeding 2/3 [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. However, there are no definitive reports on the intensity, frequency, type or duration of exercise, and further evidence on exercise methods is needed. Further evidence needs to be accumulated. The cooling therapy is a strategy to reduce the incidence of CIPN by cooling the extremities during the administration of anticancer drugs to cause vasoconstriction, thereby decreasing the amount of circulating blood flow and, consequently, the amount of anticancer drugs that flow locally. Meta-analysis analyses have reported a predominant reduction in the frequency of CIPN with paclitaxel [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. There have been no reports of serious side effects, but problems include the burden of administration on the healthcare provider and patient, and the preparation and storage of cooling equipment. In addition, cooling often causes discomfort and cannot be continued during administration. Compression therapy is a strategy to reduce the onset of CIPN by compressing the extremities during the administration of anticancer drugs to cause vasoconstriction, thereby reducing the amount of circulating blood flow and, consequently, the amount of anticancer drugs flowing locally. Compression may also have a protective effect on peripheral nerves by promoting venous and lymphatic return, thereby reducing the peripheral persistence of anticancer drugs [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In a study of patients treated with nab-paclitaxel by Tsuyuki et al, the frequency of grade 2 or higher CIPN was reduced [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], but no differences were found in patients treated with paclitaxel, which was studied by Kotani [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In addition, Kanbayashi et al. reported that there was no difference between the two groups in their comparison of compression and cooling therapy [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. As with cooling therapy, problems include the burden on both providers and patients, in particular the difficulty of wearing two pairs of gloves, the difficulty of applying the gloves, and the difficulty of applying the gloves in a way that is not easy. The problems include the difficulty of application, especially when wearing two pairs of gloves, and the preparation, storage and reusability of the compression tools.\u003c/p\u003e \u003cp\u003eIn the present study, a combination of compression and cooling therapies was used in the hope of a complementary effect that could prevent the development of CIPN in a stable manner after discomfort and difficulty in continuation, suspension or withdrawal of both therapies, and to improve the prevention rate of CIPN. When patients eligible for chemotherapy were informed of the potential preventive effect, acceptance was good in most patients. The following problems and countermeasures were encountered during the implementation of this study in actual clinical practice: (1) cooling therapy was temporarily interrupted in some cases, but the surface temperature of the peripheral fingers was maintained by alternately placing the palms and back of the hands on the cooling material. (2) When it was difficult to put on two pairs of gloves, a device was devised to facilitate putting on gloves by applying Vaseline, baby powder or potato starch to the first pair of gloves. (3) Other doctors and healthcare professionals were not aware of compression therapy and cooling therapy, and education was essential. (4) The process from prior patient explanation, measurement and purchase of gloves and stockings to implementation was centralised and concise. The results of the study showed that CIPN was significantly reduced (paclitaxel: 43.80%/19.0%, nab-paclitaxel: 60.80%/15.0%) compared to previously reported results [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], with no patients experiencing Grade 3 or higher adverse events, and most side effects from the combination therapy were minor and did not need to be addressed. The study showed that the combination was safe and effective, as most of the side effects were minor and did not require treatment. There were no cases of dose reduction or discontinuation of chemotherapy, suggesting that the drugs can be effectively delivered to patients. This is the first study to look at the preventive effect of chemotherapy in lung cancer and the combined effect of compression therapy and cooling therapy.\u003c/p\u003e \u003cp\u003eAs a limitation of this study, there is no comparison with placebo and no comparison with compression therapy alone or cooling therapy alone, so the synergistic effect of the combined therapy is not truly known. The study was also based on medical assessments, and a patient-reported assessment tool would increase the accuracy of the study. Forward-looking, large-scale clinical trials with additional cases are needed.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript. The authors did not receive support from any organization for the submitted work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u0026nbsp;\u003c/strong\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Yasuhiro Nakajima. The first draft of the manuscript was written by Yasuhiro Nakajima and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u0026nbsp;\u003c/strong\u003eDetails of the experiments are available within the article. In addition, documents related to this study have been uploaded to the website of Himeji St Mary's Hospital (Http://www.himemaria.or.jp).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompliance with Ethical Standards\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure of potential conflicts of interest:\u003c/strong\u003e The authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResearch involving Human Participants and/or Animals:\u003c/strong\u003e This study was performed in line with the principles of the Declaration of Helsinki. The study was approved by the Ethical Review Committee for Clinical Research at Himeji St Mary's Hospital in accordance with the ethical guidelines for medical research involving human subjects (approval number: S023-012,6/6/2023),\u0026nbsp;retrospectively registered.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent:\u003c/strong\u003e The study was carried out with the verbal consent of the patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish:\u0026nbsp;\u003c/strong\u003eNot Applicable.\u003c/p\u003e\u003ch2\u003eAcknowledgements:\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSeretny M, Currie GL, Sena ES et al (2014) Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. 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Brain Behav 9:e01312. https://doi.org/10.1002/brb3.1312\u003c/li\u003e\n\u003cli\u003eMizrahi D, Park SB, Li T et al (2021) Hemoglobin, body mass index, and age as risk factors for paclitaxel- and oxaliplatin-induced peripheral neuropathy. JAMA Netw Open 4:e2036695. https://doi.org/10.1001/jamanetworkopen.2020.36695\u003c/li\u003e\n\u003cli\u003eNyrop KA, Deal AM, Reeder-Hayes KE et al (2019) Patient-reported and clinician-reported chemotherapy-induced peripheral neuropathy in patients with early breast cancer: current clinical practice. Cancer 125:2945-2954. https://doi.org/10.1002/cncr.32175\u003c/li\u003e\n\u003cli\u003eRattanakrong N, Thipprasopchock S, Siriphorn A, Boonyong S (2022) Reliability and validity of the EORTC QLQ-CIPN20 (European organization for research and treatment of cancer quality of life questionnaire-chemotherapy-induced peripheral neuropathy 20-item scale) among Thai Women with Breast Cancer Undergoing taxane-Based Chemotherapy. Asian Pac J Cancer Prev 23:1547-1553. https://doi.org/10.31557/APJCP.2022.23.5.1547\u003c/li\u003e\n\u003cli\u003eLustberg M, Loprinzi C (eds) (2021). Diagnosis, Management and Emerging Strategies for Chemotherapy-Induced Neuropathy: A MASCC Book. Springer. https://doi.org/10.1007/978-3-030-78663-2 \u003c/li\u003e\n\u003cli\u003eShinde SS, Seisler D, Soori G et al (2016) Can pregabalin prevent paclitaxel-associated neuropathy?-An ACCRU pilot trial. Support Care Cancer 24:547-553. https://doi.org/10.1007/s00520-015-2807-5\u003c/li\u003e\n\u003cli\u003eKuriyama A, Endo K (2018) Goshajinkigan for prevention of chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis. Support Care Cancer 26:1051-1059. https://doi.org/10.1007/s00520-017-4028-6\u003c/li\u003e\n\u003cli\u003eHoshino N, Ganeko R, Hida K, Sakai Y (2018) Goshajinkigan for reducing chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis. Int J Clin Oncol 23:434-442. https://doi.org/10.1007/s10147-017-1229-4\u003c/li\u003e\n\u003cli\u003eCampone M, Berton-Rigaud D, Joly-Lobbedez F et al (2013) A double-blind, randomized phase Ⅱ study to evaluate the safety and efficacy of acetyl-L-carnitine in the prevention of sagopilone-induced peripheral neuropathy. Oncologist 18:1190-1191. https://doi.org/10.1634/theoncologist.2013-0061\u003c/li\u003e\n\u003cli\u003eHershman DL, Unger JM, Crew KD et al. (2018) Two-year trends of taxane-induced neuropathy in woman enrolled in a randomized trial of acetyl-L-carnitine. J Natl Cancer Inst 110:669-676. https://doi.org/10.1093/jnci/djx259\u003c/li\u003e\n\u003cli\u003eM\u0026uuml;ller J, Weiler M, Schneeweiss A et al (2021) Preventive effect of sensorimotor exercise and resistance training on chemotherapy-induced peripheral neuropathy: a randomised-controlled trial. Br J Cancer 125:955-965. https://doi.org/10.1038/s41416-021-01471-1\u003c/li\u003e\n\u003cli\u003eOhno T, Mine T, Yoshioka H et al. (2014) Management of peripheral neuropathy induced by nab-paclitaxel treatment for breast cancer. Anticancer Res 34:4213\u0026ndash;4216\u003c/li\u003e\n\u003cli\u003eKotani H, Terada M, Mori M et al (2021) Compression therapy using surgical gloves does not prevent paclitaxel-induced peripheral neuropathy: result from a double-blind phase Ⅱ trial. BMC Cancer 21:548. https://doi.org/10.1186/s12885-021-08240-6 \u003c/li\u003e\n\u003cli\u003ePharmaceuticals and Medical Devices Agency. https//www.pmda.go.jp/PmdaSearch/iyakuSearch/. Accessed February 2024.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Chemotherapy-induced peripheral neuropathy (CIPN), Compression therapy, Cooling therapy, Taxane","lastPublishedDoi":"10.21203/rs.3.rs-4337948/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4337948/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eCurrently, taxane-based cytotoxic anticancer drugs are the drug of choice for chemotherapy in various carcinomas. However, they can induce chemotherapy-induced peripheral neuropathy (CIPN), which often has a significant impact on quality of life. Currently, only duloxetine is recommended for the relief of CIPN pain, but it does not provide significant improvement and it is important to prevent the onset of CIPN. There are few reports of preventive effects on chemotherapy for lung cancer and little is known about the combination of compression and cooling therapies.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eAt our institution, we have conducted a study in patients with advanced lung cancer on a taxane-containing regimen, using a combination of compression therapy and cooling therapy, to determine the preventive effect on CIPN.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe results showed a reduction in the incidence of CIPN in the group treated with combination therapy compared with previous reports, while ensuring safety.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eWe believe that the combination of compression and cooling therapy may be useful in the prevention of CIPN.\u003c/p\u003e","manuscriptTitle":"Preventive effect of combined compression and cooling therapy on chemotherapy-induced peripheral neuropathy in taxane-based chemotherapy for lung cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-28 17:55:45","doi":"10.21203/rs.3.rs-4337948/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"96fc219a-5fc9-47c8-a1dd-3b7202d7336a","owner":[],"postedDate":"May 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-26T15:52:34+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-28 17:55:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4337948","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4337948","identity":"rs-4337948","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}