Maintaining Oxaliplatin Therapy After Hypersensitivity Reactions: Real-World Experience With a Desensitisation Protocol

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Vlachostergios, Jacqueline Connell, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8367553/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Jan, 2026 Read the published version in Clinical and Experimental Medicine → Version 1 posted 7 You are reading this latest preprint version Abstract Background: Hypersensitivity reactions (HSRs) to oxaliplatin occur in 7–25% of patients and pose a significant clinical challenge, particularly for individuals who otherwise benefit from oxaliplatin-based therapy. Although evidence supporting its efficacy remains limited, drug desensitisation protocols (DDPs) involving stepwise dose escalation have been adopted in clinical practice. This study describes the experience of a tertiary cancer centre with oxaliplatin desensitisation, focusing on recurrence of HSRs and treatment completion rates. Patients and Methods: A retrospective observational study was conducted at a comprehensive cancer centre between October 2019 and January 2024. Clinicopathological characteristics and oncological outcomes were examined for patients with gastrointestinal malignancies who received oxaliplatin-based chemotherapy using a DDP. Results: Sixty-six patients underwent oxaliplatin desensitisation (median age 60 years; 55% female). Most had colorectal cancer (CRC) (n=35, 53%) or upper gastrointestinal malignancies (n=26, 39%); 85% (n=56) were treated with palliative intent. The median number of oxaliplatin cycles prior to the first HSR was six (range 1–26). CAPOX (53%) and FOLFOX (42%) were the most common regimens associated with HSRs. Patients received a median of three cycles within the DDP (range 1–19). Most (76%) remained on their original systemic anti-cancer therapy without premature treatment modification. Sixteen patients (24%) experienced a recurrent HSR; however, 55 patients (83%) successfully completed their intended treatment. Outcomes during the desensitisation period included: no evidence of disease in eight patients (seven treated in the adjuvant setting), treatment response in 26 patients, and disease progression in 32 patients. Conclusions: Oxaliplatin desensitisation is feasible and enables most patients to continue systemic therapy, with low rates of treatment discontinuation and acceptable oncological outcomes. This approach should be considered for eligible patients who experience oxaliplatin-related HSRs to maintain access to effective chemotherapy. Figures Figure 1 Figure 2 1. Introduction Oxaliplatin is a cytotoxic agent that acts by interacting with DNA to form intrastrand and interstrand DNA cross-links, affecting DNA pairing, replication, and gene transcription, leading to cell death 1 . Oxaliplatin-based chemotherapy regimens are the standard of care in neo-adjuvant, adjuvant, and palliative settings, for malignancies mainly of the gastrointestinal tract (gastric, oesophageal, pancreatic, and colorectal cancer) 2 – 4 . Hypersensitivity reactions (HSRs) to oxaliplatin have been well described as an adverse event, with its incidence reported to be between 7.1% and 25% 5–9 , with some studies reporting even higher rates 10 , although only 0.5–3% represent severe reactions 11 , 12 . HSRs can involve every organ system including the skin and mucosal membranes (flushing, erythema, pruritus, urticaria, rash, angioedema, throat tightness, tongue swelling), respiratory (nasal congestion, sneezing, wheezing, dyspnoea, cough, O2 desaturation, chest tightness), cardiovascular (tachycardia, chest pain, presyncope, syncope, hypertension, hypotension), gastrointestinal (nausea/vomiting, diarrhoea, abdominal pain, bloating, reflux), neuromuscular (numbness/weakness, back pain, headache, rigors, seizures, unusual taste, other pain), or present with constitutional symptoms (diaphoresis, chills and fever) 13 . These are mostly IgE-mediated reactions, leading to activation of basophils, but cytokine release, characterised by increased IL-6 levels and activation of other types of inflammatory cells such as macrophages, can also participate in some of these reactions such as fever, chills and pain 13 , 14 . Non-immediate HSRs have also been described such as antibody-mediated thrombocytopenia 15 and immune complex mediated syndromes manifesting with urticaria and proteinuria 16 . Repeat exposure to oxaliplatin can be life-threatening for patients who have previously presented with HSR 17 . Since the early days of oxaliplatin use, drug desensitisation protocols (DDPs) have been employed to circumvent HSRs 18 . These protocols involve delivering the target dose of a drug in incremental amounts. This approach was adopted after it was proven that premedication with steroids and antihistamines alone was not an efficient way of preventing these reactions 19 , 20 . DDPs modify the immune response of patients, generating temporary tolerance to the causative agent by raising the anaphylactic threshold, via well-established cellular pathways 21 . DDPs have been proven to be powerful tools that enable patients to continue an oxaliplatin-based regimen without interruption, which could hinder the benefits of antineoplastic treatment and have a negative impact on cancer outcomes 22 . However, there is insufficient evidence to evaluate safety, particularly with regard to the likelihood and severity of breakthrough reactions (BTRs), i.e. repeated HSRs to oxaliplatin in patients receiving it via a DDP. Similarly, there is limited evidence to assess the effectiveness of the protocol in terms of oncological outcomes. Although evidence is still evolving, initial and breakthrough HSRs have been associated with various clinical and immunological risk factors. Several large cohort and mechanistic studies have attempted to identify predictors of oxaliplatin-related HSRs. While initial HSRs to oxaliplatin are associated with cumulative dosing and patient history 23 – 25 , breakthrough reactions during desensitisation protocols are less well studied. A more comprehensive understanding of the potential risk factors for BTRs is crucial to enable the safe and widespread implementation of DDPs. The oxaliplatin-DDP has been used extensively at our institution since March 2018, with a standardised approach consistently followed. This retrospective report summarises our real-world experience of tolerability and oncological outcomes in this patient population. 2. Methods 2.1 Study design This retrospective, single-cohort study examined patients who received oxaliplatin-based chemotherapy with a desensitisation protocol after experiencing a HSR between October 2019 and January 2024. Data were collected independently by two healthcare professionals and updated in March 2024. The study included patients with primary cancer of any site who had received at least one cycle of oxaliplatin via the desensitisation protocol, in line with local policy for assessing and managing HSRs to oxaliplatin. Patient demographics, characteristics, and outcomes were retrospectively retrieved from electronic medical records. The primary endpoint of the study was the incidence of BTRs, as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 26 . The study was approved by the Quality Improvement and Audit Committee of The Christie Hospital (Reference Number 3916). 2.2 Selection of patients for DDP Patients who were eligible for the oxaliplatin desensitisation regimen had either experienced a grade 2 HSR during their initial oxaliplatin treatment, or a grade 1 or 2 HSR during rechallenge with oxaliplatin. Patients who experienced a grade 1 HSR during the initial oxaliplatin treatment could continue with a prolonged regimen, with the oxaliplatin administered over four hours alongside routine premedication (rechallenge protocol). However, if they experienced a further HSR with any subsequent infusion, they switched to the desensitisation protocol, unless the reaction was grade 3–4. In this case, they should not receive any further oxaliplatin treatment. The decision to implement a DDP following a grade 2 reaction was guided by the treating team for each patient. Patients who experienced a grade 3 or 4 reaction or prolonged/unresolved grade 2 symptoms should not be re-treated with oxaliplatin. Patients who experienced BTRs while on the desensitisation protocol should discontinue oxaliplatin treatment permanently. Patients presenting with mild oxaliplatin-related HSRs that did not require the introduction of a DDP, and patients receiving a prolonged infusion of oxaliplatin using a rechallenge protocol, were excluded from the analysis. 2.3 Desensitisation protocol The oxaliplatin desensitisation protocol was adapted from the carboplatin desensitisation protocol used at The Christie. This was done in collaboration with other UK tertiary cancer centres and in accordance with the available evidence at the time 27 . It included premedication with oral steroids (dexamethasone 4mg BD) and oral antihistamines (cetirizine 10mg and Famotidine 40mg OD) starting the day before chemotherapy administration and continuing for a total of 3 days. Additionally, ondansetron (8mg), dexamethasone (7.6mg), chlorphenamine (10mg) were given as bolus infusions and famotidine (40mg orally) at least 30min prior to oxaliplatin initiation. The oxaliplatin was administered in four separate escalating doses over 6.5 hours. (dose 1 consisted of 1/500th of the total oxaliplatin dose infused over 90 minutes, dose 2 consisted of 1/100th of the total oxaliplatin dose infused over 90 minutes, dose 3 consisted of 1/10th of the total oxaliplatin dose infused over 90 minutes, and dose 4 consisted of the remaining oxaliplatin dose infused over 120 minutes). (Fig. 1 ). It should be noted that oxaliplatin desensitisation could only be performed in the main hospital setting and was not approved for use on the mobile chemotherapy unit. 2.4. Grading of Hypersensitivity Reactions The Common Terminology Criteria for Adverse Events, version 3.0 26 , were followed to grade the oxaliplatin-related HSRs both for the initial and breakthrough HSRs. Accordingly, grade 1 reactions were mild, with patients presenting only transient symptoms including flushing, rash, and a temperature below 38°C. Grade 2 reactions were moderate and patients presented with symptoms such as rash, urticaria, dyspnoea, and a temperature > 38.0°C. Grade 3 reactions were severe and patients presented with symptoms such as bronchospasm, angioedema/oedema and hypotension, or prolonged moderate symptoms that did not resolve. Grade 4 reactions were life-threatening and were characterised by anaphylaxis. Back pain, which is a common symptom, was considered a Grade 1 reaction when it was present as the only symptom, according to our protocol. 2.5. Outcome measures and Statistical Analysis The primary objective of this study was to evaluate the safety and efficacy of oxaliplatin DDP at our hospital. The type and severity of initial and breakthrough HSRs were summarised using absolute numbers and relative frequency tables. Oncological outcomes were also assessed and presented. These included disease response to treatment and completion of the intended treatment cycles. For neoadjuvant treatment, this was defined as completion of planned chemotherapy cycles until a pre-planned imaging evaluation was performed. For adjuvant treatment, it was defined as completion of the pre-planned chemotherapy regimen. For palliative intent, it was defined as completion of planned treatment until either a subsequent scan or other clinical factors, such as unacceptable toxicity, indicated the need to stop treatment. A secondary objective was to explore potential risk factors for BTRs, including age, sex, history of pre-existing allergies, treatment intent, previous exposure to oxaliplatin as part of an oxaliplatin-based regimen in prior lines of chemotherapy, chemotherapy regimen, grade of initial reaction, number of cycles in which the initial HSR occurred, and cumulative doses of oxaliplatin received at the time of the initial and BTR HSR. To assess statistical differences between patients who experienced a BTR and those who did not, a chi-squared test was performed on all variables. Continuous variables were categorised based on clinical relevance and previous literature to facilitate comparison. The number and percentage of patients in each category were calculated and reported using the IBM SPSS Statistics, Version 31 program. 3. Results 3.1 Patient characteristics and initial oxaliplatin reaction A total of 66 patients (36 females [55%]) with a median age of 60 years (range 36–81) were treated within the DDP. Most patients had colorectal (n = 35, 53%) or oesophago-gastric (n = 26, 39%) cancer, and the majority were treated with palliative intent (n = 56, 85%). Around half of the patients (n = 34, 52%) had oxaliplatin exposure in previous lines of chemotherapy, and 22 patients (33%) had a documented history of allergy in their electronic medical records (Table 1 ). The initial HSR was reported after a median of six cycles (range 1–26). The mean cumulative dose of oxaliplatin was 870 mg (range 130–2,295 mg). A grade 1 reaction was observed in 11 patients (17%), a grade 2 reaction in 48 patients (73%), and a grade 3 reaction in seven patients (11%). No patients experienced a grade 4 reaction. The most common symptoms were flushing/warmth (35%), dyspnoea (35%), oropharyngeal dysaesthesia/laryngospasm (24%) and pruritus (20%) (Table 2 ). One patient with oxaliplatin induced immune thrombocytopenia immediately following oxaliplatin infusion, which is considered a non-immediate HSR, was included in the study. 3.2 Breakthrough Reactions The total success rate was 76% and only sixteen patients (24%) experienced a BTR: 69% in the first cycle of DDP treatment and 31% in cycles two to six. The median number of oxaliplatin cycles on the DDP regimen was three (range 1–19), with a mean cumulative dose of 673 mg (range 90–5602mg). Most of the reactions were grade 1 or 2 (87.5%). Only two patients experienced a grade 3 reaction. The most common BTRs were flushing/warmth (n = 7/16, 44%), rash (n = 4/16, 25%), pruritus (n = 3/16, 19%), oropharyngeal dysaesthesia (n = 3/16, 19%), and gastrointestinal symptoms (e.g. diarrhoea, nausea, vomiting) (n = 3/16, 19%) (Table 2 ). No life-threatening or fatal reactions were reported in patients who received the DDP. Our protocol dictated that, once a patient experienced a BTR, oxaliplatin treatment should be permanently discontinued, regardless of the nature of the reaction. However, two patients continued their treatment with the DDP despite experiencing a BTR. In one case, oxaliplatin was continued with a 25% dose reduction at the final dilution—where the BTR had occurred—and with an additional dose of chlorphenamine and hydrocortisone administered beforehand. In the other case, treatment proceeded without any further modifications. Neither patient experienced additional HSRs. 3.3 Risk factors for Breakthrough Reactions The potential risk factors related to BTRs were analysed, including age, gender, type of cancer, allergy history, cumulative dose, curative or palliative intent, chemotherapy regimen, use of targeted agents, and oxaliplatin exposure in previous lines of chemotherapy; however, no statistically significant results were found for any of the studied parameters (Table 3 ). In patients with BTR, there was a trend of receiving fewer than three cycles of treatment (p = 0.07). Patients who did not develop HSRs received a higher median cumulative dose of oxaliplatin than those who reacted while on DDP (p = 0.01). 3.4 Oncologic outcomes Of the 66 patients in total, 34 achieved a favourable outcome in the initial scan after DDP was introduced. Of these patients, 25 were in a palliative care setting, two were receiving treatment in a neoadjuvant setting, and seven were undergoing adjuvant treatment. Fifty-five patients (83%) completed the intended number of oxaliplatin cycles, indicating that the initial reaction did not require treatment to be stopped prematurely and switched to a different chemotherapy regime (Fig. 2 ). Fifty of the patients who completed their intended treatment did not experience a BTR. Nine were treated with curative intent, two were on neoadjuvant treatment and showed some response, and sever were on adjuvant treatment. Out of those six showed no evidence of disease and one, with colorectal cancer, experienced disease recurrence. The remaining 41 patients were on palliative chemotherapy. Of these, 19 showed progressive disease (PD) on the first assessment scan after the introduction of the DDP, 14 achieved stable disease (SD), seven had a partial response (PR) and one attained a complete response (CR). Five patients who completed the intended therapy had a BTR. Four of these patients were receiving palliative treatment. Two stopped treatment due to disease progression, while the other two continued at the discretion of their oncology team: one experienced disease progression, while the other achieved stable disease (SD). The final patient was on adjuvant therapy and treatment was stopped due to other treatment-related side effects, with no evidence of recurrence. 4. Discussion Over the past two decades, oxaliplatin-related HSRs have been the subject of thorough investigation, resulting in the development of various DDP aimed at mitigating these events. Despite the publication of over 30 studies on this subject, a consensus remains elusive, and practices vary among centres according to local policies. Prominent studies in this field 13 , 16 , 28 – 31 , have shown that pre-medication regimens in desensitisation protocols typically consist of three main components: antihistamines, corticosteroids and additional agents tailored to the characteristics of the initial HSR. As oxaliplatin-related HSRs are primarily considered to be type I IgE-mediated reactions, with histamine as a key mediator, antihistamines are a consistent feature across all protocols. These generally include both H1 and H2 receptor antagonists, although the specific timing and dosage can vary. A review of H2 antagonists used for premedication in paclitaxel chemotherapy found no benefit in reducing HSRs, which calls into question their effectiveness in preventing oxaliplatin-induced HSRs 32 , 33 . Although corticosteroids are widely used to treat various inflammatory conditions, ranging from sepsis to immunotherapy-related reactions, they are not included in all desensitisation protocols. Similar to previous oncology-led approaches, our protocol incorporates the administration of high-dose of dexamethasone prior to oxaliplatin 28 , 31 . On the other hand, allergist-led protocols usually don't include corticosteroids unless the initial reaction included symptoms like chills, shivering, fever or pain. In such cases, additional agents such as intravenous fluids, ibuprofen and opioids are commonly used 13 , 29 . Furthermore, some protocols include aspirin and montelukast as part of the pre-medication regimen for patients who experienced flushing or bronchospasm during their initial HSR 13 , 16 - an approach not adopted in our protocol. The original protocol for oxaliplatin desensitisation at Brigham and Women’s Hospital involved three different dilutions administered in 12 steps over a 6-hour period 34 . However, various teams have introduced modifications to this protocol, either increasing the number of steps and dilutions 16 , 30 or modifying the protocol depending on the type and severity of the initial and breakthrough HSRs 13 , 29 . Due to the complexity of the original protocol, simplified versions using fewer dilutions and infusion steps have also been developed and studied 28 , 31 , including our own, which has been shown to be equally effective. In our study, we observed a total success rate of 76%, which is similar to that reported in previous studies, irrespective of whether multi-step or simpler graded protocols were employed 13 , 16 , 28 – 31 . This suggests that the success of the DDP may depend on other underlying factors, in addition to the number of steps or adjustments to pre-medication. A recent study proposed that 26.0% of patients with oxaliplatin-induced adverse drug reactions (ADRs) could not undergo oxaliplatin rechallenge. A specific HLA-DRB*12:01 allele has been identified as conferring sensitivity to these reactions, which could explain the consistent outcome observed across the studies 35 . Only two patients (3% of the population) experienced a grade 3 HSR, and there were no grade 4 or 5 (fatal) HSRs. This is consistent with similar studies who reported 5% 31 -7% 28 of severe grade 3 and 4 reactions. The overwhelming majority of BTRs were classified as Type I HSR. No type II reactions involving antibody-mediated immune reactions in which IgG or IgM antibodies bind to antigens on the surface of cells or extracellular matrix, leading to cell destruction, inflammation, or dysfunction. were observed, and none of the patient’s required hospitalisation. The management of BTRs during DDPs remains challenging. While permanent discontinuation of oxaliplatin is recommended by our protocol, several strategies have been explored to mitigate their occurrence. Other approaches involving simplified DDPs included switching to a 12-step desensitisation protocol, which was only partially effective, as two-thirds of patients still experienced further reactions and had to discontinue treatment 31 . More recent reports have also explored the efficacy of new immunomodulating agents such as tocilizumab 36 , omalizumab 29 , 37 or acalabrutinib 38 , as an attempt to avoid BTRs with promising results. However, larger studies are needed to confirm the effectiveness of these methods. It is challenging to identify patients predisposed to BTRs due to the absence of reliable, consistent outcome data. Madrigal-Burgaleta et al. 39 found that atopy was a risk factor for BTRs in a mixed cohort of patients receiving taxanes, platinum compounds, or biological agents (OR: 2.16; 95% CI: 1.5–14.06; p = 0.03). However, previous studies have not identified age, gender or atopy as risk factors for BTRs 13 , 40 , 41 , which is consistent with our results. Caiado et al. showed that receiving more than ten platinum infusions was a risk factor for BTRs (OR: 4.11, 95% CI: [1.17–14.52]; p = 0.03), and this was confirmed as an independent risk factor in a multivariate analysis 41 . However, our data indicate that the cumulative dose of oxaliplatin was not a significant risk factor 37 . This difference may be due to the fact that their population included patients who had also received other platinum treatments, such as cisplatin or carboplatin 29 . Caiado et al. also so demonstrated that an initial HSR of grade 2 or 3 increased the risk of BTRs (OR: 2.19, 95% CI: [0.38–12.79]), though this difference was not statistically significant 41 . Similarly, we found no difference in the incidence of BTRs between patients with mild/moderate and severe initial HSR. Silver et al. suggested that patients with BTRs tend to do so within the first three cycles of DDP 13 , and our data did reflect the same trend. Efforts have been made to study blood biomarkers and skin testing (ST) as predictors of response to DDP. Although serum tryptase is generally considered a reliable marker of anaphylaxis, research has shown that it is not useful in predicting BTRs 13 . IL-6 levels are significantly raised in patients presenting with cytokine release syndrome 13 . An increased total IgE level (> 100 U/mL) was shown to be a risk factor for BTRs, (OR: 8.24, 95% CI: [2.06–30.02]) but this study involved a mixed population who received different types of platinum agents 41 . Studies regarding the ST protocol are controversial. Some studies have shown that positive oxaliplatin skin testing can predict a response to DDP 16 , 40 , and a stratification protocol has been implemented for the use of DDP 30 , suggesting positive and negative predictive values of 92% and 56.4%, respectively. However, other studies have not confirmed these outcomes 13 , 41 . Unfortunately, such parameters were unavailable and therefore not included in our study. We categorised both the initial and the breakthrough reactions based on the clinical presentation and severity of the reaction, according to the CTCAE criteria for allergic reactions/ hypersensitivity (version 3.0) 26 . However, attempts have been made to endophenotype oxaliplatin HSRs according to their underlying pathophysiology, separating type II reactions (pruritus, urticaria, angioedema, nasal congestion, sneezing, wheezing, coughing, throat tightness, tongue swelling and hypotension), which are IgE-mediated reactions related to increased tryptase levels, from cytokine release reactions (chest pain, back pain, headache, other pain, chills, rigours, fever, numbness/weakness and hypertension/hypotension), which are characterised by increased IL-6 levels, as well as HSRs that can be mediated by either of these pathophysiological mechanisms 13 . This classification not only allows adjustments to the initial DDP depending on the type of reaction, but also modifications to the DDP if a patient experiences a HSR 13 , 29 . While the primary objective of DDP is to enable treatment to continue in patients with HSRs, it is ultimately crucial for maintaining favourable oncological outcomes. Previous studies have shown that desensitisation protocols for various chemotherapy agents can achieve similar oncological outcomes to standard, non-desensitised regimens 42 , 43 . Nevertheless, large-scale data remains scarce. The largest study of oxaliplatin DDP to date was conducted by Alonso Martinez et al. , who reported a PD rate of 35% 31 . In our cohort, 83% of patients completed their intended treatment; however, 44% experienced disease progression. Eighteen per cent of patients discontinued treatment due to other toxicities, while 44% completed their full course. Interpreting progression rates in these settings is complex owing to the heterogeneity of patient populations, which often include individuals undergoing both radical and palliative treatments, as well as those with different primary diseases. Further research involving larger, more homogeneous patient groups is needed to establish whether oxaliplatin-related HSRs or the nature of the desensitisation protocol itself may have a negative impact on oncological outcomes. Our study has several limitations. Data on initial and breakthrough HSRs were collected retrospectively from electronic medical records at a single centre. Consequently, the characterisation and grading of reactions depended heavily on the quality and completeness of clinical documentation, which may have varied depending on the experience of the healthcare professional involved. The cohort predominantly included patients with Grade 1–2 reactions, as our local policy excludes those with moderate-to-severe initial reactions from desensitisation. Additionally, as the study reflects the experience of a single centre using a desensitisation protocol that has not yet been adopted by other teams, the findings may be difficult to generalise. The small sample size also precluded a multivariate analysis to explore potential risk factors for breakthrough reactions. Despite these limitations, our results suggest that the DDP is a reliable treatment for patients with oxaliplatin reactions, provided the appropriate patients are selected. Conclusion To our knowledge, this is one of the largest published series of patients treated with oxaliplatin using a structured desensitisation protocol, which further supports the safety and clinical efficacy of this approach in managing oxaliplatin-induced HSRs. The high overall success rate highlights the value of desensitisation in enabling patients to continue with life-prolonging chemotherapy, even following a significant hypersensitivity event. However, some patients will still experience BTRs or be unable to tolerate re-exposure despite desensitisation. There is still a need to establish standardised, consensus-driven DDPs across institutions. This would facilitate multi-centre collaborations, increase statistical power and enable more rigorous exploration of predictive biomarkers and clinical risk factors associated with DDP failure. Crucially, identifying patients at high risk of desensitisation failure early on could prompt timely referral to specialist allergy services. In these settings, expert allergists can implement tailored interventions, such as stepwise desensitisation and adjunctive pharmacological premedication, thereby maximising the likelihood of treatment continuity and oncological benefit. In conclusion, although DDPs are a valuable tool for overcoming oxaliplatin HSRs, the future lies in improving patient selection, personalising management and encouraging collaboration to optimise outcomes in different clinical settings. Declarations Institutional Review Board Statement: This study was conducted in accordance with the Declaration of Helsinki. The study was approved by the Quality Improvement and Audit Committee of The Christie Hospital (Reference Number 3916). Informed Consent Statement :The study was approved by The Christie NHS Foundation Trust Research and Ethics Committee. The requirement for individual informed consent was waived due to the retrospective nature of the analysis and use of anonymised data. Data Availability Statement: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Acknowledgments: The authors have no acknowledgements to declare. Conflicts of Interest: M.S. reports personal fees from Servier Global, Merck, UK, and Amgen, UK, outside the submitted work. All other authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results. Funding Declaration : No funding was received for this study. References Graham J, Muhsin M, Kirkpatrick P, Oxaliplatin. Nat Rev Drug Discov. 2004;3:11–2. André T, et al. Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer. N Engl J Med. 2004;350:2343–51. Sánchez-Gundín J, Fernández-Carballido AM, Martínez-Valdivieso L, Barreda-Hernández D. Torres-Suárez, A. I. New Trends in the Therapeutic Approach to Metastatic Colorectal Cancer. Int J Med Sci. 2018;15:659–65. Al-Batran S-E, et al. 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Makrilia N, Syrigou E, Kaklamanos I, Manolopoulos L, Saif MW. Hypersensitivity Reactions Associated with Platinum Antineoplastic Agents: A Systematic Review. Met Based Drugs 2010, 1–11 (2010). Rassy E, et al. Rechallenge After Oxaliplatin-Induced Hypersensitivity Reactions. JAMA Oncol. 2023;9:434. Jimenez-Rodriguez T-W, et al. Differential presentation of hypersensitivity reactions to carboplatin and oxaliplatin: Phenotypes, endotypes, and management with desensitization. Allergy. 2024;79:679–89. Wang AL, Patil SU, Long AA, Banerji A. Risk-stratification protocol for carboplatin and oxaliplatin hypersensitivity: repeat skin testing to identify drug allergy. Ann Allergy Asthma Immunol. 2015;115:422–8. Alonso Martinez S, et al. Simplified Graded Infusion Strategy for Mitigation of Oxaliplatin Hypersensitivity. Clin Colorectal Cancer. 2022;21:149–53. Boulanger J, et al. Management of hypersensitivity to platinum- and taxane-based chemotherapy: cepo review and clinical recommendations. Curr Oncol. 2014;21:e630–41. Foreman E, Polwart C, Walker A, Chambers P. Histamine-2 (H 2 ) antagonists can be safely removed from standard paclitaxel premedication regimens. Br J Clin Pharmacol. 2022;88:4191–8. Castells MC, et al. Hypersensitivity reactions to chemotherapy: Outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol. 2008;122:574–80. Hsu H-C, et al. Clinical characteristics and genetic HLA marker for patients with oxaliplatin-induced adverse drug reactions. Allergology Int. 2024. https://doi.org/10.1016/j.alit.2024.03.003 . Liao J, Jiang M. Case report: Tocilizumab for hypersensitivity reaction after oxaliplatin in a patient with NK/T-cell lymphoma. Front Pharmacol. 2024;15:1471038. Penella J, et al. Successful Desensitization to Oxaliplatin After a Single Initial Dose of Omalizumab in a Patient With Elevated IgE Levels. J Investig Allergol Clin Immunol. 2020;30:293–5. Erickson KA, et al. Prevention of allergic reactions during oxaliplatin desensitization through inhibition of Bruton tyrosine kinase. J Allergy Clin Immunol. 2024;154:222–e2284. Madrigal-Burgaleta R, et al. A Large Single-Hospital Experience Using Drug Provocation Testing and Rapid Drug Desensitization in Hypersensitivity to Antineoplastic and Biological Agents. J Allergy Clin Immunol Pract. 2019;7:618–32. Gorgulu Akin B, et al. Rapid drug desensitization with platin-based chemotherapy: Analysis of risk factors for breakthrough reactions. World Allergy Organ J. 2022;15:100619. Caiado J, Brás R, Paulino M, Costa L, Castells M. Rapid desensitization to antineoplastic drugs in an outpatient immunoallergology clinic. Ann Allergy Asthma Immunol. 2020;125:325–e3331. Sloane D, et al. Safety, Costs, and Efficacy of Rapid Drug Desensitizations to Chemotherapy and Monoclonal Antibodies. J Allergy Clin Immunol Pract. 2016;4:497–504. Castells M. Rapid Desensitization for Hypersensitivity Reactions to Medications. Immunol Allergy Clin North Am. 2009;29:585–606. Tables Table 1. Baseline Demographics and characteristics of participants Number, n (%) Gender Male Female 30 (45) 36 (55) Age median (range) 60 (36 - 81) Type of Cancer Colorectal Gastric Oesophageal Gastro-Oesophageal Pancreatic NET Appendiceal Cholangiocarcinoma 35 (53%) 11 (17%) 6 (9%) 9 (14%) 1 (2%) 1 (2%) 2 (3%) 1 (2%) Regime during initial hypersensitivity reaction OxMdG/ Rechallenge OxMdG OxMdG + Bevacizumab OxCap / Rechallenge OxCap OxCap + Trastuzumab OxCap + Nivolumab OxCap + Pembrolizumab FOLFIRINOX FLOT 26 (39%) 2 (2%) 31 (47%) 1 (2%) 1 (2%) 2 (3%) 2 (3%) 1 (2%) Treatment intention Palliative Adjuvant Neo-Adjuvant 56 (85%) 8 (12%) 2 (3%) Oxaliplatin exposure in previous lines of chemotherapy Yes No 34 (52%) 32 (48%) History of previous allergies Yes No 22 (33%) 44 (67%) Table 2. Characteristics of initial and Breakthrough Reactions Oxaliplatin cycles prior to initial reaction median (range) Desensitisation cycles - median (range) 6 (1-26) 3 (1-19) Severity of Reaction Initial - Nr (%) Breakthrough Nr (%) Grade 1 11 (17) 7 (43.8) Grade 2 48 (73) 7 (43.8) Grade 3 7 (11) 2 (12.5) Grade 4 0 (0) 0 (0) Type of Reaction Initial Nr (%) Breakthrough Nr (%) Pruritus 13 (20) 3(19) Rash 10 (15) 4 (25) Erythema 7 (11) 2 (13) Urticaria 10 (15) 1 (6) Flushing/Warmth 23 (35) 7 (44) Dyspnoea 23 (35) 0 (0) Oropharyngeal dysaesthesia/Laryngospasm 16 (24) 3 (19) GI Symptoms (diarrhoea, nausea, vomiting) 11 (17) 3 (19) Pyrexia 4 (6) 0 (0) Rigors 2 (3) 0 (0) Chest pain/Tachycardia 2 (3) 0 (0) Angioedema 0 (0) 0 (0) Back pain 4 (6) 2 (13) Hypertension (SBP >170mmHg) 3 (5) 2 (13) Hypotension (SBP < 90mmHg) 4 (6) 0 (0) Bronchospasm 1 (2) 1 (6) Hypoxia (SaO2 < 94%) 2 (3) 0 (0) Numbness/ paraesthesia/weakness 6 (9) 0 (0) Miscellaneous neurological symptoms (visual blurriness/slurred speech/imbalance/dizziness) 7 (11) 0 (0) Table 3. Risk factors for Breakthrough reactions Risk factors Group Categories Chi-square (x2) test p-Value Age <65 / ≥65 0.102 0.750 Gender Male/Female 3.664 0.160 Type of Cancer UGI/LGI/HPB 0.748 0.668 Treatment intention Curative/palliative 1.302 0.254 Regime before the reaction CAPOX/FOLFOX/ FOLFIRINOX/FLOT 3.241 0.663 Targeted agents Panitumumab/Bevacizumab /Nivolumab/Trastuzumab 0.206 0.650 Previous Exposure to oxaliplatin Yes/No 0.019 0.889 Initial Grading of the reaction Mild-moderate/Severe 0.003 0.957 Hx of Allergy Yes/No 2.640 0.104 No of cycles in desensitisation protocol 3 or less/ >3 3.284 0.070 Cumulative dose at the time of initial reaction 1000 1.142 0.565 Cumulative dose at the time of end of treatment 1000 9.300 0.010 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 21 Jan, 2026 Read the published version in Clinical and Experimental Medicine → Version 1 posted Editorial decision: Accepted 28 Dec, 2025 Reviews received at journal 27 Dec, 2025 Reviewers agreed at journal 24 Dec, 2025 Reviewers invited by journal 19 Dec, 2025 Editor assigned by journal 18 Dec, 2025 Submission checks completed at journal 18 Dec, 2025 First submitted to journal 15 Dec, 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. We do this by developing innovative software and high quality services for the global research community. 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16:30:34","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":113797,"visible":true,"origin":"","legend":"","description":"","filename":"835de68b953b45938461085eda9255f41structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8367553/v1/8e429ec108e52b97b11c2fb0.xml"},{"id":99188399,"identity":"5bd4d11d-272c-4244-906b-109e1be68f2d","added_by":"auto","created_at":"2025-12-30 00:18:37","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":130533,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8367553/v1/ab298079a312b089e172f492.html"},{"id":99188389,"identity":"db1ad9aa-dfb0-4742-879a-7545121137dc","added_by":"auto","created_at":"2025-12-30 00:18:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":98763,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOxaliplatin Desensitisation Protocol\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is a schematic diagram of the oxaliplatin desensitisation protocol that was used in our Institution for this study.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8367553/v1/561bae5a9f7295b0ccdb7738.png"},{"id":99316798,"identity":"37a5a09e-5921-4176-bc72-348121b46f16","added_by":"auto","created_at":"2025-12-31 16:29:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":144052,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOncological\u003c/strong\u003e \u003cstrong\u003eoutcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis figure illustrates the oncological outcomes of patients categorised by the presence or absence of BTR, treatment intent, and completion of treatment. BTR, Breakthrough Reactions, DDP Drug-Desensitisation Protocol, Pts: patients, PD: Progression of Disease, CR: Complete Response, PR: Partial Response, SD: Stable Disease, NED: No Evidence of Disease\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e* Include patients who completed their intended treatment despite having undergone BTR\u003c/em\u003e.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8367553/v1/50ae48821a27fcb7120405e3.png"},{"id":101152871,"identity":"86d8b53a-62cf-4d88-bf46-9ccb454c5131","added_by":"auto","created_at":"2026-01-26 16:13:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1356839,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8367553/v1/70918676-4c2a-4560-bb5b-8a3db52a0b53.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Maintaining Oxaliplatin Therapy After Hypersensitivity Reactions: Real-World Experience With a Desensitisation Protocol","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eOxaliplatin is a cytotoxic agent that acts by interacting with DNA to form intrastrand and interstrand DNA cross-links, affecting DNA pairing, replication, and gene transcription, leading to cell death\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Oxaliplatin-based chemotherapy regimens are the standard of care in neo-adjuvant, adjuvant, and palliative settings, for malignancies mainly of the gastrointestinal tract (gastric, oesophageal, pancreatic, and colorectal cancer)\u003csup\u003e\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Hypersensitivity reactions (HSRs) to oxaliplatin have been well described as an adverse event, with its incidence reported to be between 7.1% and 25%\u003csup\u003e5\u0026ndash;9\u003c/sup\u003e, with some studies reporting even higher rates\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, although only 0.5\u0026ndash;3% represent severe reactions\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. HSRs can involve every organ system including the skin and mucosal membranes (flushing, erythema, pruritus, urticaria, rash, angioedema, throat tightness, tongue swelling), respiratory (nasal congestion, sneezing, wheezing, dyspnoea, cough, O2 desaturation, chest tightness), cardiovascular (tachycardia, chest pain, presyncope, syncope, hypertension, hypotension), gastrointestinal (nausea/vomiting, diarrhoea, abdominal pain, bloating, reflux), neuromuscular (numbness/weakness, back pain, headache, rigors, seizures, unusual taste, other pain), or present with constitutional symptoms (diaphoresis, chills and fever)\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. These are mostly IgE-mediated reactions, leading to activation of basophils, but cytokine release, characterised by increased IL-6 levels and activation of other types of inflammatory cells such as macrophages, can also participate in some of these reactions such as fever, chills and pain\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Non-immediate HSRs have also been described such as antibody-mediated thrombocytopenia\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e and immune complex mediated syndromes manifesting with urticaria and proteinuria\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Repeat exposure to oxaliplatin can be life-threatening for patients who have previously presented with HSR\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSince the early days of oxaliplatin use, drug desensitisation protocols (DDPs) have been employed to circumvent HSRs\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. These protocols involve delivering the target dose of a drug in incremental amounts. This approach was adopted after it was proven that premedication with steroids and antihistamines alone was not an efficient way of preventing these reactions\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. DDPs modify the immune response of patients, generating temporary tolerance to the causative agent by raising the anaphylactic threshold, via well-established cellular pathways\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. DDPs have been proven to be powerful tools that enable patients to continue an oxaliplatin-based regimen without interruption, which could hinder the benefits of antineoplastic treatment and have a negative impact on cancer outcomes\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHowever, there is insufficient evidence to evaluate safety, particularly with regard to the likelihood and severity of breakthrough reactions (BTRs), i.e. repeated HSRs to oxaliplatin in patients receiving it via a DDP. Similarly, there is limited evidence to assess the effectiveness of the protocol in terms of oncological outcomes. Although evidence is still evolving, initial and breakthrough HSRs have been associated with various clinical and immunological risk factors. Several large cohort and mechanistic studies have attempted to identify predictors of oxaliplatin-related HSRs. While initial HSRs to oxaliplatin are associated with cumulative dosing and patient history\u003csup\u003e\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e, breakthrough reactions during desensitisation protocols are less well studied. A more comprehensive understanding of the potential risk factors for BTRs is crucial to enable the safe and widespread implementation of DDPs.\u003c/p\u003e \u003cp\u003eThe oxaliplatin-DDP has been used extensively at our institution since March 2018, with a standardised approach consistently followed. This retrospective report summarises our real-world experience of tolerability and oncological outcomes in this patient population.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study design\u003c/h2\u003e \u003cp\u003eThis retrospective, single-cohort study examined patients who received oxaliplatin-based chemotherapy with a desensitisation protocol after experiencing a HSR between October 2019 and January 2024. Data were collected independently by two healthcare professionals and updated in March 2024.\u003c/p\u003e \u003cp\u003eThe study included patients with primary cancer of any site who had received at least one cycle of oxaliplatin via the desensitisation protocol, in line with local policy for assessing and managing HSRs to oxaliplatin. Patient demographics, characteristics, and outcomes were retrospectively retrieved from electronic medical records. The primary endpoint of the study was the incidence of BTRs, as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 \u003csup\u003e26\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e The study was approved by the Quality Improvement and Audit Committee of The Christie Hospital (Reference Number 3916).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Selection of patients for DDP\u003c/h2\u003e \u003cp\u003ePatients who were eligible for the oxaliplatin desensitisation regimen had either experienced a grade 2 HSR during their initial oxaliplatin treatment, or a grade 1 or 2 HSR during rechallenge with oxaliplatin. Patients who experienced a grade 1 HSR during the initial oxaliplatin treatment could continue with a prolonged regimen, with the oxaliplatin administered over four hours alongside routine premedication (rechallenge protocol). However, if they experienced a further HSR with any subsequent infusion, they switched to the desensitisation protocol, unless the reaction was grade 3\u0026ndash;4. In this case, they should not receive any further oxaliplatin treatment. The decision to implement a DDP following a grade 2 reaction was guided by the treating team for each patient. Patients who experienced a grade 3 or 4 reaction or prolonged/unresolved grade 2 symptoms should not be re-treated with oxaliplatin. Patients who experienced BTRs while on the desensitisation protocol should discontinue oxaliplatin treatment permanently.\u003c/p\u003e \u003cp\u003ePatients presenting with mild oxaliplatin-related HSRs that did not require the introduction of a DDP, and patients receiving a prolonged infusion of oxaliplatin using a rechallenge protocol, were excluded from the analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Desensitisation protocol\u003c/h2\u003e \u003cp\u003eThe oxaliplatin desensitisation protocol was adapted from the carboplatin desensitisation protocol used at The Christie. This was done in collaboration with other UK tertiary cancer centres and in accordance with the available evidence at the time \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. It included premedication with oral steroids (dexamethasone 4mg BD) and oral antihistamines (cetirizine 10mg and Famotidine 40mg OD) starting the day before chemotherapy administration and continuing for a total of 3 days. Additionally, ondansetron (8mg), dexamethasone (7.6mg), chlorphenamine (10mg) were given as bolus infusions and famotidine (40mg orally) at least 30min prior to oxaliplatin initiation. The oxaliplatin was administered in four separate escalating doses over 6.5 hours. (dose 1 consisted of 1/500th of the total oxaliplatin dose infused over 90 minutes, dose 2 consisted of 1/100th of the total oxaliplatin dose infused over 90 minutes, dose 3 consisted of 1/10th of the total oxaliplatin dose infused over 90 minutes, and dose 4 consisted of the remaining oxaliplatin dose infused over 120 minutes). (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIt should be noted that oxaliplatin desensitisation could only be performed in the main hospital setting and was not approved for use on the mobile chemotherapy unit.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Grading of Hypersensitivity Reactions\u003c/h2\u003e \u003cp\u003eThe Common Terminology Criteria for Adverse Events, version 3.0\u003csup\u003e26\u003c/sup\u003e, were followed to grade the oxaliplatin-related HSRs both for the initial and breakthrough HSRs. Accordingly, grade 1 reactions were mild, with patients presenting only transient symptoms including flushing, rash, and a temperature below 38\u0026deg;C. Grade 2 reactions were moderate and patients presented with symptoms such as rash, urticaria, dyspnoea, and a temperature\u0026thinsp;\u0026gt;\u0026thinsp;38.0\u0026deg;C. Grade 3 reactions were severe and patients presented with symptoms such as bronchospasm, angioedema/oedema and hypotension, or prolonged moderate symptoms that did not resolve. Grade 4 reactions were life-threatening and were characterised by anaphylaxis.\u003c/p\u003e \u003cp\u003eBack pain, which is a common symptom, was considered a Grade 1 reaction when it was present as the only symptom, according to our protocol.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Outcome measures and Statistical Analysis\u003c/h2\u003e \u003cp\u003eThe primary objective of this study was to evaluate the safety and efficacy of oxaliplatin DDP at our hospital. The type and severity of initial and breakthrough HSRs were summarised using absolute numbers and relative frequency tables. Oncological outcomes were also assessed and presented. These included disease response to treatment and completion of the intended treatment cycles. For neoadjuvant treatment, this was defined as completion of planned chemotherapy cycles until a pre-planned imaging evaluation was performed. For adjuvant treatment, it was defined as completion of the pre-planned chemotherapy regimen. For palliative intent, it was defined as completion of planned treatment until either a subsequent scan or other clinical factors, such as unacceptable toxicity, indicated the need to stop treatment.\u003c/p\u003e \u003cp\u003eA secondary objective was to explore potential risk factors for BTRs, including age, sex, history of pre-existing allergies, treatment intent, previous exposure to oxaliplatin as part of an oxaliplatin-based regimen in prior lines of chemotherapy, chemotherapy regimen, grade of initial reaction, number of cycles in which the initial HSR occurred, and cumulative doses of oxaliplatin received at the time of the initial and BTR HSR.\u003c/p\u003e \u003cp\u003eTo assess statistical differences between patients who experienced a BTR and those who did not, a chi-squared test was performed on all variables. Continuous variables were categorised based on clinical relevance and previous literature to facilitate comparison. The number and percentage of patients in each category were calculated and reported using the IBM SPSS Statistics, Version 31 program.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Patient characteristics and initial oxaliplatin reaction\u003c/h2\u003e \u003cp\u003eA total of 66 patients (36 females [55%]) with a median age of 60 years (range 36\u0026ndash;81) were treated within the DDP. Most patients had colorectal (n\u0026thinsp;=\u0026thinsp;35, 53%) or oesophago-gastric (n\u0026thinsp;=\u0026thinsp;26, 39%) cancer, and the majority were treated with palliative intent (n\u0026thinsp;=\u0026thinsp;56, 85%). Around half of the patients (n\u0026thinsp;=\u0026thinsp;34, 52%) had oxaliplatin exposure in previous lines of chemotherapy, and 22 patients (33%) had a documented history of allergy in their electronic medical records (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe initial HSR was reported after a median of six cycles (range 1\u0026ndash;26). The mean cumulative dose of oxaliplatin was 870 mg (range 130\u0026ndash;2,295 mg). A grade 1 reaction was observed in 11 patients (17%), a grade 2 reaction in 48 patients (73%), and a grade 3 reaction in seven patients (11%). No patients experienced a grade 4 reaction. The most common symptoms were flushing/warmth (35%), dyspnoea (35%), oropharyngeal dysaesthesia/laryngospasm (24%) and pruritus (20%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). One patient with oxaliplatin induced immune thrombocytopenia immediately following oxaliplatin infusion, which is considered a non-immediate HSR, was included in the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Breakthrough Reactions\u003c/h2\u003e \u003cp\u003eThe total success rate was 76% and only sixteen patients (24%) experienced a BTR: 69% in the first cycle of DDP treatment and 31% in cycles two to six. The median number of oxaliplatin cycles on the DDP regimen was three (range 1\u0026ndash;19), with a mean cumulative dose of 673 mg (range 90\u0026ndash;5602mg). Most of the reactions were grade 1 or 2 (87.5%). Only two patients experienced a grade 3 reaction. The most common BTRs were flushing/warmth (n\u0026thinsp;=\u0026thinsp;7/16, 44%), rash (n\u0026thinsp;=\u0026thinsp;4/16, 25%), pruritus (n\u0026thinsp;=\u0026thinsp;3/16, 19%), oropharyngeal dysaesthesia (n\u0026thinsp;=\u0026thinsp;3/16, 19%), and gastrointestinal symptoms (e.g. diarrhoea, nausea, vomiting) (n\u0026thinsp;=\u0026thinsp;3/16, 19%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). No life-threatening or fatal reactions were reported in patients who received the DDP.\u003c/p\u003e \u003cp\u003eOur protocol dictated that, once a patient experienced a BTR, oxaliplatin treatment should be permanently discontinued, regardless of the nature of the reaction. However, two patients continued their treatment with the DDP despite experiencing a BTR. In one case, oxaliplatin was continued with a 25% dose reduction at the final dilution\u0026mdash;where the BTR had occurred\u0026mdash;and with an additional dose of chlorphenamine and hydrocortisone administered beforehand. In the other case, treatment proceeded without any further modifications. Neither patient experienced additional HSRs.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Risk factors for Breakthrough Reactions\u003c/h2\u003e \u003cp\u003eThe potential risk factors related to BTRs were analysed, including age, gender, type of cancer, allergy history, cumulative dose, curative or palliative intent, chemotherapy regimen, use of targeted agents, and oxaliplatin exposure in previous lines of chemotherapy; however, no statistically significant results were found for any of the studied parameters (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In patients with BTR, there was a trend of receiving fewer than three cycles of treatment (p\u0026thinsp;=\u0026thinsp;0.07). Patients who did not develop HSRs received a higher median cumulative dose of oxaliplatin than those who reacted while on DDP (p\u0026thinsp;=\u0026thinsp;0.01).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Oncologic outcomes\u003c/h2\u003e \u003cp\u003eOf the 66 patients in total, 34 achieved a favourable outcome in the initial scan after DDP was introduced. Of these patients, 25 were in a palliative care setting, two were receiving treatment in a neoadjuvant setting, and seven were undergoing adjuvant treatment.\u003c/p\u003e \u003cp\u003eFifty-five patients (83%) completed the intended number of oxaliplatin cycles, indicating that the initial reaction did not require treatment to be stopped prematurely and switched to a different chemotherapy regime (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFifty of the patients who completed their intended treatment did not experience a BTR. Nine were treated with curative intent, two were on neoadjuvant treatment and showed some response, and sever were on adjuvant treatment. Out of those six showed no evidence of disease and one, with colorectal cancer, experienced disease recurrence. The remaining 41 patients were on palliative chemotherapy. Of these, 19 showed progressive disease (PD) on the first assessment scan after the introduction of the DDP, 14 achieved stable disease (SD), seven had a partial response (PR) and one attained a complete response (CR).\u003c/p\u003e \u003cp\u003eFive patients who completed the intended therapy had a BTR. Four of these patients were receiving palliative treatment. Two stopped treatment due to disease progression, while the other two continued at the discretion of their oncology team: one experienced disease progression, while the other achieved stable disease (SD). The final patient was on adjuvant therapy and treatment was stopped due to other treatment-related side effects, with no evidence of recurrence.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eOver the past two decades, oxaliplatin-related HSRs have been the subject of thorough investigation, resulting in the development of various DDP aimed at mitigating these events. Despite the publication of over 30 studies on this subject, a consensus remains elusive, and practices vary among centres according to local policies.\u003c/p\u003e \u003cp\u003eProminent studies in this field\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan additionalcitationids=\"CR29 CR30\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e, have shown that pre-medication regimens in desensitisation protocols typically consist of three main components: antihistamines, corticosteroids and additional agents tailored to the characteristics of the initial HSR. As oxaliplatin-related HSRs are primarily considered to be type I IgE-mediated reactions, with histamine as a key mediator, antihistamines are a consistent feature across all protocols. These generally include both H1 and H2 receptor antagonists, although the specific timing and dosage can vary. A review of H2 antagonists used for premedication in paclitaxel chemotherapy found no benefit in reducing HSRs, which calls into question their effectiveness in preventing oxaliplatin-induced HSRs\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAlthough corticosteroids are widely used to treat various inflammatory conditions, ranging from sepsis to immunotherapy-related reactions, they are not included in all desensitisation protocols. Similar to previous oncology-led approaches, our protocol incorporates the administration of high-dose of dexamethasone prior to oxaliplatin\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. On the other hand, allergist-led protocols usually don't include corticosteroids unless the initial reaction included symptoms like chills, shivering, fever or pain. In such cases, additional agents such as intravenous fluids, ibuprofen and opioids are commonly used\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Furthermore, some protocols include aspirin and montelukast as part of the pre-medication regimen for patients who experienced flushing or bronchospasm during their initial HSR\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e - an approach not adopted in our protocol.\u003c/p\u003e \u003cp\u003eThe original protocol for oxaliplatin desensitisation at Brigham and Women\u0026rsquo;s Hospital involved three different dilutions administered in 12 steps over a 6-hour period\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. However, various teams have introduced modifications to this protocol, either increasing the number of steps and dilutions\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e or modifying the protocol depending on the type and severity of the initial and breakthrough HSRs\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Due to the complexity of the original protocol, simplified versions using fewer dilutions and infusion steps have also been developed and studied \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e, including our own, which has been shown to be equally effective.\u003c/p\u003e \u003cp\u003eIn our study, we observed a total success rate of 76%, which is similar to that reported in previous studies, irrespective of whether multi-step or simpler graded protocols were employed \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan additionalcitationids=\"CR29 CR30\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. This suggests that the success of the DDP may depend on other underlying factors, in addition to the number of steps or adjustments to pre-medication. A recent study proposed that 26.0% of patients with oxaliplatin-induced adverse drug reactions (ADRs) could not undergo oxaliplatin rechallenge. A specific HLA-DRB*12:01 allele has been identified as conferring sensitivity to these reactions, which could explain the consistent outcome observed across the studies \u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOnly two patients (3% of the population) experienced a grade 3 HSR, and there were no grade 4 or 5 (fatal) HSRs. This is consistent with similar studies who reported 5%\u003csup\u003e31\u003c/sup\u003e -7%\u003csup\u003e28\u003c/sup\u003e of severe grade 3 and 4 reactions. The overwhelming majority of BTRs were classified as Type I HSR. No type II reactions involving antibody-mediated immune reactions in which IgG or IgM antibodies bind to antigens on the surface of cells or extracellular matrix, leading to cell destruction, inflammation, or dysfunction. were observed, and none of the patient\u0026rsquo;s required hospitalisation.\u003c/p\u003e \u003cp\u003eThe management of BTRs during DDPs remains challenging. While permanent discontinuation of oxaliplatin is recommended by our protocol, several strategies have been explored to mitigate their occurrence. Other approaches involving simplified DDPs included switching to a 12-step desensitisation protocol, which was only partially effective, as two-thirds of patients still experienced further reactions and had to discontinue treatment \u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. More recent reports have also explored the efficacy of new immunomodulating agents such as tocilizumab\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e, omalizumab \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003eor acalabrutinib \u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e, as an attempt to avoid BTRs with promising results. However, larger studies are needed to confirm the effectiveness of these methods.\u003c/p\u003e \u003cp\u003eIt is challenging to identify patients predisposed to BTRs due to the absence of reliable, consistent outcome data. Madrigal-Burgaleta et al.\u003csup\u003e39\u003c/sup\u003e found that atopy was a risk factor for BTRs in a mixed cohort of patients receiving taxanes, platinum compounds, or biological agents (OR: 2.16; 95% CI: 1.5\u0026ndash;14.06; p\u0026thinsp;=\u0026thinsp;0.03). However, previous studies have not identified age, gender or atopy as risk factors for BTRs \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e, which is consistent with our results.\u003c/p\u003e \u003cp\u003eCaiado et al. showed that receiving more than ten platinum infusions was a risk factor for BTRs (OR: 4.11, 95% CI: [1.17\u0026ndash;14.52]; p\u0026thinsp;=\u0026thinsp;0.03), and this was confirmed as an independent risk factor in a multivariate analysis \u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. However, our data indicate that the cumulative dose of oxaliplatin was not a significant risk factor \u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e. This difference may be due to the fact that their population included patients who had also received other platinum treatments, such as cisplatin or carboplatin\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Caiado \u003cem\u003eet al.\u003c/em\u003e also so demonstrated that an initial HSR of grade 2 or 3 increased the risk of BTRs (OR: 2.19, 95% CI: [0.38\u0026ndash;12.79]), though this difference was not statistically significant \u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. Similarly, we found no difference in the incidence of BTRs between patients with mild/moderate and severe initial HSR. Silver et al. suggested that patients with BTRs tend to do so within the first three cycles of DDP \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e, and our data did reflect the same trend.\u003c/p\u003e \u003cp\u003eEfforts have been made to study blood biomarkers and skin testing (ST) as predictors of response to DDP. Although serum tryptase is generally considered a reliable marker of anaphylaxis, research has shown that it is not useful in predicting BTRs \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. IL-6 levels are significantly raised in patients presenting with cytokine release syndrome \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. An increased total IgE level (\u0026gt;\u0026thinsp;100 U/mL) was shown to be a risk factor for BTRs, (OR: 8.24, 95% CI: [2.06\u0026ndash;30.02]) but this study involved a mixed population who received different types of platinum agents \u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. Studies regarding the ST protocol are controversial. Some studies have shown that positive oxaliplatin skin testing can predict a response to DDP \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e, and a stratification protocol has been implemented for the use of DDP \u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e, suggesting positive and negative predictive values of 92% and 56.4%, respectively. However, other studies have not confirmed these outcomes \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. Unfortunately, such parameters were unavailable and therefore not included in our study.\u003c/p\u003e \u003cp\u003eWe categorised both the initial and the breakthrough reactions based on the clinical presentation and severity of the reaction, according to the CTCAE criteria for allergic reactions/ hypersensitivity (version 3.0)\u003csup\u003e26\u003c/sup\u003e. However, attempts have been made to endophenotype oxaliplatin HSRs according to their underlying pathophysiology, separating type II reactions (pruritus, urticaria, angioedema, nasal congestion, sneezing, wheezing, coughing, throat tightness, tongue swelling and hypotension), which are IgE-mediated reactions related to increased tryptase levels, from cytokine release reactions (chest pain, back pain, headache, other pain, chills, rigours, fever, numbness/weakness and hypertension/hypotension), which are characterised by increased IL-6 levels, as well as HSRs that can be mediated by either of these pathophysiological mechanisms\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. This classification not only allows adjustments to the initial DDP depending on the type of reaction, but also modifications to the DDP if a patient experiences a HSR \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWhile the primary objective of DDP is to enable treatment to continue in patients with HSRs, it is ultimately crucial for maintaining favourable oncological outcomes. Previous studies have shown that desensitisation protocols for various chemotherapy agents can achieve similar oncological outcomes to standard, non-desensitised regimens \u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e,\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e. Nevertheless, large-scale data remains scarce.\u003c/p\u003e \u003cp\u003eThe largest study of oxaliplatin DDP to date was conducted by Alonso Martinez \u003cem\u003eet al.\u003c/em\u003e, who reported a PD rate of 35% \u003csup\u003e31\u003c/sup\u003e. In our cohort, 83% of patients completed their intended treatment; however, 44% experienced disease progression. Eighteen per cent of patients discontinued treatment due to other toxicities, while 44% completed their full course. Interpreting progression rates in these settings is complex owing to the heterogeneity of patient populations, which often include individuals undergoing both radical and palliative treatments, as well as those with different primary diseases. Further research involving larger, more homogeneous patient groups is needed to establish whether oxaliplatin-related HSRs or the nature of the desensitisation protocol itself may have a negative impact on oncological outcomes.\u003c/p\u003e \u003cp\u003eOur study has several limitations. Data on initial and breakthrough HSRs were collected retrospectively from electronic medical records at a single centre. Consequently, the characterisation and grading of reactions depended heavily on the quality and completeness of clinical documentation, which may have varied depending on the experience of the healthcare professional involved. The cohort predominantly included patients with Grade 1\u0026ndash;2 reactions, as our local policy excludes those with moderate-to-severe initial reactions from desensitisation. Additionally, as the study reflects the experience of a single centre using a desensitisation protocol that has not yet been adopted by other teams, the findings may be difficult to generalise. The small sample size also precluded a multivariate analysis to explore potential risk factors for breakthrough reactions. Despite these limitations, our results suggest that the DDP is a reliable treatment for patients with oxaliplatin reactions, provided the appropriate patients are selected.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTo our knowledge, this is one of the largest published series of patients treated with oxaliplatin using a structured desensitisation protocol, which further supports the safety and clinical efficacy of this approach in managing oxaliplatin-induced HSRs. The high overall success rate highlights the value of desensitisation in enabling patients to continue with life-prolonging chemotherapy, even following a significant hypersensitivity event.\u003c/p\u003e \u003cp\u003eHowever, some patients will still experience BTRs or be unable to tolerate re-exposure despite desensitisation. There is still a need to establish standardised, consensus-driven DDPs across institutions. This would facilitate multi-centre collaborations, increase statistical power and enable more rigorous exploration of predictive biomarkers and clinical risk factors associated with DDP failure.\u003c/p\u003e \u003cp\u003eCrucially, identifying patients at high risk of desensitisation failure early on could prompt timely referral to specialist allergy services. In these settings, expert allergists can implement tailored interventions, such as stepwise desensitisation and adjunctive pharmacological premedication, thereby maximising the likelihood of treatment continuity and oncological benefit.\u003c/p\u003e \u003cp\u003eIn conclusion, although DDPs are a valuable tool for overcoming oxaliplatin HSRs, the future lies in improving patient selection, personalising management and encouraging collaboration to optimise outcomes in different clinical settings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eInstitutional Review Board Statement:\u003c/strong\u003e This study was conducted in accordance with the Declaration of Helsinki. The study was approved by the Quality Improvement and Audit Committee of The Christie Hospital (Reference Number 3916).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent Statement\u003c/strong\u003e:The study was approved by The Christie NHS Foundation Trust Research and Ethics Committee. The requirement for individual informed consent was waived due to the retrospective nature of the analysis and use of anonymised data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement:\u003c/strong\u003e The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e The authors have no acknowledgements to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e\u0026nbsp; M.S. reports personal fees from Servier Global, Merck, UK, and Amgen, UK, outside the submitted work. All other authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Declaration\u003c/strong\u003e: No funding was received for this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGraham J, Muhsin M, Kirkpatrick P, Oxaliplatin. Nat Rev Drug Discov. 2004;3:11\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAndr\u0026eacute; T, et al. Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer. N Engl J Med. 2004;350:2343\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS\u0026aacute;nchez-Gund\u0026iacute;n J, Fern\u0026aacute;ndez-Carballido AM, Mart\u0026iacute;nez-Valdivieso L, Barreda-Hern\u0026aacute;ndez D. 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Prevention of allergic reactions during oxaliplatin desensitization through inhibition of Bruton tyrosine kinase. J Allergy Clin Immunol. 2024;154:222\u0026ndash;e2284.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMadrigal-Burgaleta R, et al. A Large Single-Hospital Experience Using Drug Provocation Testing and Rapid Drug Desensitization in Hypersensitivity to Antineoplastic and Biological Agents. J Allergy Clin Immunol Pract. 2019;7:618\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGorgulu Akin B, et al. Rapid drug desensitization with platin-based chemotherapy: Analysis of risk factors for breakthrough reactions. World Allergy Organ J. 2022;15:100619.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCaiado J, Br\u0026aacute;s R, Paulino M, Costa L, Castells M. Rapid desensitization to antineoplastic drugs in an outpatient immunoallergology clinic. Ann Allergy Asthma Immunol. 2020;125:325\u0026ndash;e3331.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSloane D, et al. Safety, Costs, and Efficacy of Rapid Drug Desensitizations to Chemotherapy and Monoclonal Antibodies. J Allergy Clin Immunol Pract. 2016;4:497\u0026ndash;504.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCastells M. Rapid Desensitization for Hypersensitivity Reactions to Medications. Immunol Allergy Clin North Am. 2009;29:585\u0026ndash;606.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"609\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003eTable 1. Baseline Demographics and characteristics of participants\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.5747%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49.4253%;\"\u003e\n \u003cp\u003eNumber, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.5747%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49.4253%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e30 (45)\u003c/p\u003e\n \u003cp\u003e36 (55)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.5747%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49.4253%;\"\u003e\n \u003cp\u003e60 (36 - 81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.5747%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of Cancer\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eColorectal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eGastric\u003c/p\u003e\n \u003cp\u003eOesophageal\u003c/p\u003e\n \u003cp\u003eGastro-Oesophageal\u003c/p\u003e\n \u003cp\u003ePancreatic\u003c/p\u003e\n \u003cp\u003eNET\u003c/p\u003e\n \u003cp\u003eAppendiceal\u003c/p\u003e\n \u003cp\u003eCholangiocarcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49.4253%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e35 (53%)\u003c/p\u003e\n \u003cp\u003e11 (17%)\u003c/p\u003e\n \u003cp\u003e6 (9%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;9 (14%)\u003c/p\u003e\n \u003cp\u003e1 (2%)\u003c/p\u003e\n \u003cp\u003e1 (2%)\u003c/p\u003e\n \u003cp\u003e2 (3%)\u003c/p\u003e\n \u003cp\u003e1 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.5747%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRegime during initial hypersensitivity reaction\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eOxMdG/ Rechallenge OxMdG\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eOxMdG + Bevacizumab\u003c/p\u003e\n \u003cp\u003eOxCap / Rechallenge OxCap\u003c/p\u003e\n \u003cp\u003eOxCap + Trastuzumab\u003c/p\u003e\n \u003cp\u003eOxCap + Nivolumab\u003cbr\u003e\u0026nbsp;OxCap + Pembrolizumab\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFOLFIRINOX\u003c/p\u003e\n \u003cp\u003eFLOT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49.4253%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26 (39%)\u003c/p\u003e\n \u003cp\u003e2 (2%)\u003c/p\u003e\n \u003cp\u003e31 (47%)\u003c/p\u003e\n \u003cp\u003e1 (2%)\u003c/p\u003e\n \u003cp\u003e1 (2%)\u003c/p\u003e\n \u003cp\u003e2 (3%)\u003c/p\u003e\n \u003cp\u003e2 (3%)\u003c/p\u003e\n \u003cp\u003e1 (2%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.5747%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment intention\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePalliative\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAdjuvant\u003c/p\u003e\n \u003cp\u003eNeo-Adjuvant\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49.4253%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e56 (85%)\u003c/p\u003e\n \u003cp\u003e8 (12%)\u003c/p\u003e\n \u003cp\u003e2 (3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.5747%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOxaliplatin exposure in previous lines of chemotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eYes\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49.4253%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e34 (52%)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32 (48%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.5747%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistory of previous allergies\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Yes\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49.4253%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22 (33%)\u003c/p\u003e\n \u003cp\u003e44 (67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"610\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003eTable 2. Characteristics of initial and Breakthrough Reactions\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003eOxaliplatin cycles prior to initial reaction\u0026nbsp;\u003c/p\u003e\n \u003cp\u003emedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003eDesensitisation cycles - median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e6 (1-26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e3 (1-19)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSeverity of Reaction\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInitial - Nr (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBreakthrough Nr (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e11 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e7 (43.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e48 (73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e7 (43.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e7 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e2 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eType of Reaction\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInitial Nr\u003c/strong\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBreakthrough Nr (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePruritus\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e13 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e3(19)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRash\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e10 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e4 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eErythema\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e7 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e2 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUrticaria\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e10 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e1 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFlushing/Warmth\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e23 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e7 (44)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDyspnoea\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e23 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOropharyngeal dysaesthesia/Laryngospasm\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e16 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e3 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGI Symptoms (diarrhoea, nausea, vomiting)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e11 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e3 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePyrexia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e4 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRigors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e2 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChest pain/Tachycardia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e2 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAngioedema\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBack pain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e4 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e2 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypertension (SBP \u0026gt;170mmHg)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e3 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e2 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypotension (SBP \u0026lt; 90mmHg)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e4 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBronchospasm\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e1 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e1 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypoxia (SaO2 \u0026lt; 94%)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e2 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumbness/ paraesthesia/weakness\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e6 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 46.0656%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMiscellaneous neurological symptoms\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(visual blurriness/slurred speech/imbalance/dizziness)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3934%;\"\u003e\n \u003cp\u003e7 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.541%;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Risk factors for Breakthrough reactions\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"616\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0632%;\"\u003e\n \u003cp\u003eRisk factors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.6045%;\"\u003e\n \u003cp\u003eGroup Categories\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.5008%;\"\u003e\n \u003cp\u003eChi-square (x2) test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8314%;\"\u003e\n \u003cp\u003ep-Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0632%;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.6045%;\"\u003e\n \u003cp\u003e\u0026lt;65 / \u0026ge;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.5008%;\"\u003e\n \u003cp\u003e0.102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8314%;\"\u003e\n \u003cp\u003e0.750\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0632%;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.6045%;\"\u003e\n \u003cp\u003eMale/Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.5008%;\"\u003e\n \u003cp\u003e3.664\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8314%;\"\u003e\n \u003cp\u003e0.160\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0632%;\"\u003e\n \u003cp\u003eType of Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.6045%;\"\u003e\n \u003cp\u003eUGI/LGI/HPB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.5008%;\"\u003e\n \u003cp\u003e0.748\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8314%;\"\u003e\n \u003cp\u003e0.668\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0632%;\"\u003e\n \u003cp\u003eTreatment intention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.6045%;\"\u003e\n \u003cp\u003eCurative/palliative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.5008%;\"\u003e\n \u003cp\u003e1.302\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8314%;\"\u003e\n \u003cp\u003e0.254\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0632%;\"\u003e\n \u003cp\u003eRegime before the reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.6045%;\"\u003e\n \u003cp\u003eCAPOX/FOLFOX/\u003c/p\u003e\n \u003cp\u003eFOLFIRINOX/FLOT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.5008%;\"\u003e\n \u003cp\u003e3.241\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8314%;\"\u003e\n \u003cp\u003e0.663\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0632%;\"\u003e\n \u003cp\u003eTargeted agents\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.6045%;\"\u003e\n \u003cp\u003ePanitumumab/Bevacizumab\u003c/p\u003e\n \u003cp\u003e/Nivolumab/Trastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.5008%;\"\u003e\n \u003cp\u003e0.206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8314%;\"\u003e\n \u003cp\u003e0.650\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0632%;\"\u003e\n \u003cp\u003ePrevious Exposure to oxaliplatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.6045%;\"\u003e\n \u003cp\u003eYes/No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.5008%;\"\u003e\n \u003cp\u003e0.019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8314%;\"\u003e\n \u003cp\u003e0.889\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0632%;\"\u003e\n \u003cp\u003eInitial Grading of the reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.6045%;\"\u003e\n \u003cp\u003eMild-moderate/Severe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.5008%;\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8314%;\"\u003e\n \u003cp\u003e0.957\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0632%;\"\u003e\n \u003cp\u003eHx of Allergy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.6045%;\"\u003e\n \u003cp\u003eYes/No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.5008%;\"\u003e\n \u003cp\u003e2.640\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8314%;\"\u003e\n \u003cp\u003e0.104\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0632%;\"\u003e\n \u003cp\u003eNo of cycles in desensitisation protocol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.6045%;\"\u003e\n \u003cp\u003e3 or less/ \u0026gt;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.5008%;\"\u003e\n \u003cp\u003e3.284\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8314%;\"\u003e\n \u003cp\u003e0.070\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0632%;\"\u003e\n \u003cp\u003eCumulative dose at the time of initial reaction\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.6045%;\"\u003e\n \u003cp\u003e\u0026lt;500/500-1000/\u0026gt;1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.5008%;\"\u003e\n \u003cp\u003e1.142\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8314%;\"\u003e\n \u003cp\u003e0.565\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0632%;\"\u003e\n \u003cp\u003eCumulative dose at the time of end of treatment\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 31.6045%;\"\u003e\n \u003cp\u003e\u0026lt;500/ 500-1000/\u0026gt;1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.5008%;\"\u003e\n \u003cp\u003e9.300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8314%;\"\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\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":"clinical-and-experimental-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"clem","sideBox":"Learn more about [Clinical and Experimental Medicine](https://www.springer.com/journal/10238)","snPcode":"10238","submissionUrl":"https://submission.nature.com/new-submission/10238/3","title":"Clinical and Experimental Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8367553/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8367553/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHypersensitivity reactions (HSRs) to oxaliplatin occur in 7–25% of patients and pose a significant clinical challenge, particularly for individuals who otherwise benefit from oxaliplatin-based therapy. Although evidence supporting its efficacy remains limited, drug desensitisation protocols (DDPs) involving stepwise dose escalation have been adopted in clinical practice. This study describes the experience of a tertiary cancer centre with oxaliplatin desensitisation, focusing on recurrence of HSRs and treatment completion rates.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients and Methods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA retrospective observational study was conducted at a comprehensive cancer centre between October 2019 and January 2024. Clinicopathological characteristics and oncological outcomes were examined for patients with gastrointestinal malignancies who received oxaliplatin-based chemotherapy using a DDP.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSixty-six patients underwent oxaliplatin desensitisation (median age 60 years; 55% female). Most had colorectal cancer (CRC) (n=35, 53%) or upper gastrointestinal malignancies (n=26, 39%); 85% (n=56) were treated with palliative intent. The median number of oxaliplatin cycles prior to the first HSR was six (range 1–26). CAPOX (53%) and FOLFOX (42%) were the most common regimens associated with HSRs.\u003c/p\u003e\n\u003cp\u003ePatients received a median of three cycles within the DDP (range 1–19). Most (76%) remained on their original systemic anti-cancer therapy without premature treatment modification. Sixteen patients (24%) experienced a recurrent HSR; however, 55 patients (83%) successfully completed their intended treatment. Outcomes during the desensitisation period included: no evidence of disease in eight patients (seven treated in the adjuvant setting), treatment response in 26 patients, and disease progression in 32 patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOxaliplatin desensitisation is feasible and enables most patients to continue systemic therapy, with low rates of treatment discontinuation and acceptable oncological outcomes. This approach should be considered for eligible patients who experience oxaliplatin-related HSRs to maintain access to effective chemotherapy.\u003c/p\u003e","manuscriptTitle":"Maintaining Oxaliplatin Therapy After Hypersensitivity Reactions: Real-World Experience With a Desensitisation Protocol","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-30 00:18:32","doi":"10.21203/rs.3.rs-8367553/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accepted","date":"2025-12-28T17:39:16+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-27T13:20:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"97315214208552434937719171183514441695","date":"2025-12-24T12:24:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-19T09:42:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-18T10:49:41+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-18T10:48:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"Clinical and Experimental Medicine","date":"2025-12-15T14:35:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"clinical-and-experimental-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"clem","sideBox":"Learn more about [Clinical and Experimental Medicine](https://www.springer.com/journal/10238)","snPcode":"10238","submissionUrl":"https://submission.nature.com/new-submission/10238/3","title":"Clinical and Experimental Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"19724343-b9bb-4dda-a0e3-2987fe734de7","owner":[],"postedDate":"December 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-26T16:10:09+00:00","versionOfRecord":{"articleIdentity":"rs-8367553","link":"https://doi.org/10.1007/s10238-025-02035-w","journal":{"identity":"clinical-and-experimental-medicine","isVorOnly":false,"title":"Clinical and Experimental Medicine"},"publishedOn":"2026-01-21 15:58:20","publishedOnDateReadable":"January 21st, 2026"},"versionCreatedAt":"2025-12-30 00:18:32","video":"","vorDoi":"10.1007/s10238-025-02035-w","vorDoiUrl":"https://doi.org/10.1007/s10238-025-02035-w","workflowStages":[]},"version":"v1","identity":"rs-8367553","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8367553","identity":"rs-8367553","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}