Oxaliplatin-induced Hypersensitivity Reactions Research Articles

Oxaliplatin-induced hypersensitivity reactions: risk factors and management.

Chemotherapy-related adverse reactions have been steadily increasing in recent years. In patients who develop oxaliplatin-induced hypersensitivity reactions (HSRs), prognosis and quality of life are adversely affected. Proper management of cancer patients enables them to safely receive first-line treatments. This study aimed to assess the risk factors in oxaliplatin-induced HSRs and the effectiveness of the rapid desensitization protocol. In the study, 57 patients treated with oxaliplatin between October 2019 and August 2020 in the Medical Oncology Department of Elazig City Hospital were retrospectively evaluated. We analyzed patients' clinical histories to reveal any associations with the development of oxaliplatin-induced HSRs. Moreover, we re-evaluated 11 patients with oxaliplatin-induced HSRs through infusion time or desensitization procedures. Of 57 patients treated with oxaliplatin, 11 (19.3%) had HSRs. Patients with HSRs were younger and had higher peripheral blood eosinophil counts than those without HSRs (p=0.004, p=0.020, respectively). Prolongation of the infusion time was effective in the re-administration of oxaliplatin in six of the hypersensitive patients. Rapid desensitization protocol was performed for a total of 11 cycles in four patients with recurrent HSRs, and their chemotherapy regimens were successfully completed. This retrospective study has revealed that younger ages and higher peripheral eosinophil counts could be predictive for oxaliplatin-induced HSR. Furthermore, the study confirms that prolongation of the infusion time and rapid desensitization protocol are effective in patients with HSRs.

Rechallenge After Oxaliplatin-Induced Hypersensitivity Reactions

This cohort study assesses the outcome of oxaliplatin desensitization for patients with gastrointestinal cancers who experienced hypersensitivity reactions after oxaliplatin infusion.

Interdisciplinary Healthcare Team Experience of Carboplatin and Oxaliplatin Desensitizations in a Tertiary Referral University Hospital.

Repeated exposure to platinum compounds increases the risk of immunoglobulin E-mediated immediate hypersensitivity reactions (HSR). To date, many different desensitization protocols with varying success rates have been reported. The presented study is aimed at disseminating the real-world experience of an interdisciplinary healthcare team focusing on platin desensitization. This is a cross-sectional, retrospective study of 7 female patients with carboplatin- or oxaliplatin-induced HSRs. After a discussion with the oncologist and the patient, desensitization protocols were performed by a team consisting of an allergy and immunology specialist, a clinical pharmacist, and a nurse. Clinical data were extracted from the patients' medical records, and HSRs were reviewed and classified by an allergist according to severity and type. Twenty-five desensitization protocols were carried out for patients with carboplatin- or oxaliplatin-induced HSRs (N=4 and N=3, respectively; age range: 54-66). Two of the patients did not experience any HSR during a total of 8 desensitization cycles. The other patients had grade 1-3 HSRs on 15 cycles, which were successfully managed by oxygen and/or pharmacological interventions and infusions were resumed at a lower rate after stabilization of the patient. Compared to baseline, serum tryptase levels were elevated during HSRs (4.77±0.21 vs 9.50±1.71, P=0.028). All the patients were able to finish the treatment protocol and receive full chemotherapeutic doses. Interdisciplinary teams may facilitate the preparation and administration of platinum-based chemotherapeutics and increase the success rates of desensitization protocols for platin-based chemotherapy, where the concentration and application of drugs differ from standard procedure.

Audit on Incidences of Oxaliplatin Induced Hypersensitivity Reactions during Infusion in Day Care Oncology at a Tertiary Care Hospital, Karachi, Pakistan

Audit on Incidences of Oxaliplatin Induced Hypersensitivity Reactions during Infusion in Day Care Oncology at a Tertiary Care Hospital, Karachi, Pakistan

Clinical Features of Oxaliplatin-induced Hypersensitivity Reactions in Chinese Patients: A Retrospective Multicenter Analysis.

The characteristics of oxaliplatin-induced hypersensitivity reactions (HSRs) in Chinese patients were investigated to provide a reference for patients treated with oxaliplatin. The study reviewed the records of patients who developed oxaliplatin-induced HSRs in 17 hospitals from May 2016 to May 2017. We collected and analyzed the basic information, history of oxaliplatin administration and premedication treatments, chemotherapy cycles, HSR symptoms, and the management and outcomes of these patients. Oxaliplatin-induced HSRs were recorded in 137 patients who had been treated with oxaliplatin-containing regimens. Five different chemotherapy regimens were applied. The median infusion cycle when oxaliplatin-induced HSRs occurred was 7, and HSRs occurred during or shortly after oxaliplatin infusion. Most of the patients experienced grade 1 or grade 2 HSRs with mild symptoms of pruritis (49.64%), flushing (46.72%), chest discomfort (26.28%), and urticaria (25.55%). The majority of the patients completely recovered from HSRs following treatment with antihistamines and dexamethasone. Seven patients completed chemotherapy with oxaliplatin after the symptoms resolved with proper management. The results indicate that oxaliplatin-induced HSRs remain an important issue in safely and successfully fulfilling oxaliplatin-containing chemotherapy. Further studies are needed to analyze the risk factors and establish prophylaxis for such reactions.

Intervention for oxaliplatin-induced hypersensitivity in China: a cross-sectional internet-based survey*

Abstract Objective This cross-sectional study aimed at investigating the intervention status and the influence of oncologists on oxaliplatin-induced hypersensitivity reactions (OIHR). Methods Snowball sampling was used to send questionnaires to oncologists in various provinces and cities in China, via the internet, to collect data on their socio-demographic characteristics, the occurrence of OIHR, and the current status of interventions. One-way ANOVA and T-test of geographic samples were used to explore the relationship between the incidence of OIHR and intervention measures. Results A total of 401 valid questionnaires were collected, most respondents were 30-40 years old, and most oncologists had 5 years of working experience. The proportions of glucocorticoid and H1 receptor antagonist use for OIHR prevention were 67.83% and 38.65%, respectively. The proportion of oncologists with longer working years and higher professional titles who used glucocorticoids for OIHR prevention was higher, and the observed OIHR incidence was lower. Pretreatment with glucocorticoids may be an effective preventive measure and can reduce the incidence of the OXA allergic reactions (P < 0.05). Conclusion The risk awareness of junior oncologists to OIHR prevention should be strengthened, and clinical efficacy evaluation of glucocorticoids in OIHR prevention should be further promoted.

Clinical Analysis of Hypersensitivity Reactions to Oxaliplatin Among Colorectal Cancer Patients.

This study investigated the characteristics of oxaliplatin-induced hypersensitivity reactions (HSRs) and evaluated the efficacy of premedication for controlling HSRs among colorectal cancer patients. A retrospective study was performed on the clinical records of 291 patients with colorectal cancer in The Tenth People’s Hospital of Shanghai from January 2008 to January 2016. Patients who experienced HSRs to oxaliplatin were compared with those who did not. A total of 291 colorectal cancer patients received oxaliplatin, with 39 (13.40%) experiencing HSRs. Oxaliplatin-free interval and premedication with dexamethasone and antihistamine were independent variables for oxaliplatin-related HSRs. Rechallenging patients with premedication was successful in 72.2% of the patients who successfully completed their treatment. Attention should be paid to patients with any prior exposure to oxaliplatin. Patients with grades 1 and 2 HSRs can successfully rechallenge with oxaliplatin and complete their treatment by premedication with dexamethasone and antihistamine.

Clinical Features of Oxaliplatin Induced Hypersensitivity Reactions and Therapeutic Approaches.

Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan.

A validation study of preventing oxaliplatin-induced hypersensitivity reactions by dexamethasone: The AVOID trial.

727 Background: Patients treated with oxaliplatin are at risk for hypersensitivity reactions. The incidence of hypersensitivity reactions in clinical practice is estimated to be 12% to 20%. Prescribing information says that oxaliplatin is incompatible in solution with alkaline medications or media and must not be mixed these or administered simultaneously through the same infusion line. Because steroid is alkaline, the coinfusion of steroids and oxaliplatin can make oxaliplatin unstable due to the elevation of pH; further, the effectiveness of steroid in this therapy is unknown. Therefore, dexamethasone is routinely given to patients before they receive chemotherapy. However, we have reported that the pH after the addition of DEX (6.6 mg) to oxaliplatin was less than 7.4, and there is possibility that hypersensitivity reactions to oxaliplatin could have been prevented by coinfusion of dexamethasone (DEX) (Yoshida et al.2012 ASCO-GI) but just in a retrospective study. This prospective study was undertaken to evaluate the effectiveness of coinfusion of DEX to oxaliplatin for controlling hypersensitivity reactions caused by oxaliplatin. Methods: The AVOID trial is a prospective, multicenter, open-label, single-arm, phase II trial investigating hypersensitivity reactions to oxaliplatin could have been prevented by coinfusion of DEX. The study included 73 patients who received XELOX or XELOX +bevacizumab therapy for colorectal cancer. In all the patients, oxaliplatin (130mg/m²) was administered in combination with DEX (6.6 mg). Results: Hypersensitivity reactions developed in 3 patients (4.1%). Respiratory symptoms, ocular symptoms and anaphylaxis were not observed in 73 patients. The three patients experienced cutaneous reaction (erythema: grade1). Grade 3 or higher hemotoxicity was noted in 13.7% of the patients, and grade 3 or higher nonhematological toxicity was noted in 13.7%. The response rate was 58.1%. Conclusions: This trial supports coinfusion of dexamethasone and oxaliplatin reduced oxaliplatin-related hypersensitivity reactions. This effective approach should be considered for all patients who receive oxaliplatin, allowing treatment to be completed as planned. Clinical trial information: UMIN000009742.

Hypersensitivity reactions associated with oxaliplatin and their clinical management

Introduction: Oxaliplatin, has become an integral part of the medical treatment of colorectal cancer and other malignancies. Increased use of the drug during the last decade, has led to increased occurrence of oxaliplatin-induced hypersensitivity reactions (HSRs), posing a significant challenge for clinicians. This article aims to review the existing literature regarding the incidence, clinical presentation, pathophysiology, risk factors and current management of oxaliplatin-induced HSRs.Areas covered: A systematic review of the English literature published in PubMed and Medline was undertaken. The clinical manifestations of HSRs were found to be variable and unpredictable. These reactions should be an important concern, as their potential life-threatening risks can force doctors to stop treatment and seek alternatives, which may be less effective, not as well tolerated and/or more expensive. There are a few strategies to prevent these reactions so that patients can still benefit from oxaliplatin. Such strategies include the use of premedication (steroid and antagonists of type I and II histamine receptors), prolonged infusion time and desensitization.Expert opinion: The presented management strategies as well as novel diagnostic tools including skin/intradermal tests and specific IgE have shown promising results. However, future research and validation are warranted in bigger clinical trials.

Serum lactate dehydrogenase levels as a predictive marker of oxaliplatin-induced hypersensitivity reactions in Japanese patients with advanced colorectal cancer.

Objective: Clinical laboratory test data obtained prior to treatments were previously analyzed from the standpoint of susceptibility to hypersensitivity reactions in patients treated with the platimun anticancer agent, oxaliplatin (L-OHP). In the present study, the time course from the first to last cycle of the treatment was additionally analyzed to determine a better predictor of these reactions.Methods: A total of 20 laboratory test data were obtained from 108 Japanese patients with advanced colorectal cancer who were treated with the L-OHP-containing regimens, FOLFOX4 and/or mFOLFOX6. The averages and variation coefficients (CV%) of the data until the last cycle of the treatment were compared between patients with hypersensitivity reactions and those without.Results: The average serum lactate dehydrogenase (LDH) level was lower in patients with grade 1/2 reactions (P=0.016), whereas its CV% value was higher in patients with grade 3/4 reactions (P=0.005) than in those without reactions. An increase in serum LDH levels was observed in some patients with grade 3/4 reactions as the cycle number increased, and thereafter hypersensitivity reactions occurred. This phenomenon was not always observed, but was never detected in patients with grade 1/2 reactions.Conclusions: Serum LDH levels may be a predictive marker of hypersensitivity reactions in patients treated with L-OHP. Further extensive examinations with a larger number of patients are needed to establish a patient management strategy.

P2-083 - Oxaliplatin-Induced Hypersensitivity Reactions in Patients with Advanced Colorectal Cancer in a Single Hospital

ABSTRACT Oxaliplatin is a third-generation platinum agent indicated for the treatment of colorectal cancer. It is regarded as a high risk for the development of hypersensitivity reactions. Clinical date from 119 patients with colorectal cancer were analyzed, who were treated with oxaliplatin containing regimens (FOLFOX4, mFOLOX6, Xelox, SOX) between April 2007 and January 2012. Eight males and nine females had hypersensitivity reactions. The 17 patients were 43–75 years (median 63 years), total cycle number of therapy with oxaliplatin were 2–19 cycles (median 9 cycles). The severity of hypersensitivity reactions was assessed by using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Five cases had grade 1, 11 cases grade 2 and 1 case had grade 3 hypersensitivity reactions. An immediate hypersensitivity reaction showed itching, rash, stomachache, vomit and choking. Oxygen saturation was measured continuously. Hypoxemia was diagnosed for patients and they were given oxygen. The oxaliplatin infusion was withheld and substituted with fluid support. Chlorpheniramine maleate and mPSL were administered to alleviate the hypersensitivity reactions. There was no mortality, and no one required intensive care. One case could resume chemotherapy with oxaliplatin by strong pretreatment. On the basis of our experience, we consider the hypersensitivity reactions to oxialiplatin, essential medications for the hypersensitivity reactions and the course in our hospital that we can try to treat with oxaliplatin again.

Dexamethasone as a means for controlling vascular pain caused by the administration of oxaliplatin via the peripheral vein and also for controlling oxaliplatin-induced hypersensitivity reactions.

662 Background: With the recent development of XELOX therapy involving oral administration of drug preparations, etc., implantation of a CV port can be now avoided. However, vascular pain (pain in the peripheral veins) occasionally requires switching of the drip infusion route during XELOX therapy. Some investigators reported that addition of steroids to oxaliplatin drip infusion is useful in controlling vascular pain. However, the pharmacological use of steroids can make oxaliplatin unstable due to the elevation of pH; further, the effectiveness of oxaliplatin in this therapy is unknown because of lack of published data. This study was undertaken to evaluate the effectiveness of dexamethasone (DEX) in infusion solution containing oxaliplatin for controlling vascular pain caused by the administration of oxaliplatin via the peripheral vein. Methods: The study included 47 patients (33 males and 14 females; median age, 64) who received XELOX + bevacizumab for metastatic colorectal cancer without implantation of a CV port. In all the patients, oxaliplatin (130 mg/m2) was administered in combination with DEX (6.6 mg) via the peripheral vein. Results: Vascular pain developed in 34 patients (72.3%), but it was transient. In only 1 of the 34 patients, the drip infusion route had to be switched to the opposite side because of vascular pain. No patients required CV port implantation. Grade 3 or higher hemotoxicity was noted in 14.9% of the patients, and grade 3 or higher nonhematological toxicity was noted in 21.2% of the patients. The response rate was 61.7%. Among 47 patients, no patients experienced hypersensitivity reactions to oxaliplatin. Conclusions: Addition of DEX to oxaliplatin drip infusion controlled vascular pain caused by the administration of oxaliplatin via the peripheral vein. The response rate to this therapy combined with the use of DEX suggests that DEX probably does not exert adverse effects on the therapy, ie, it does not affect the stability of oxaliplatin by elevating the pH. Furthermore, coinfusion of DEX to oxaliplatin may be a useful preventive method for oxaliplatin-induced hypersensitivity.

Dexamethasone as a Means Not Only for Controlling Vascular Pain Caused by the Administration of Oxaliplatin Via the Peripheral Vein But Also for Controlling Oxaliplatin- Induced Hypersensitivity Reactions

Background and Aims: With the recent development of capecitabine and oxaliplatin (XELOX) therapy, implantation of a Central Venous (CV) port can be now avoided. However, vascular pain occasionally requires switching of the drip infusion route. Some investigators reported that addition of steroids to oxaliplatin drip infusion is useful in controlling vascular pain. However, the pharmacological use of steroids can make oxaliplatin unstable due to the elevation of pH; further, the effectiveness of steroid in this therapy is unknown. This study was undertaken to evaluate the effectiveness of dexamethasone (DEX) for controlling vascular pain caused by the administration of oxaliplatin via the peripheral vein. Study design: Retrospective study. Place and duration of the Study: Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, between April 2010 and November 2011. Methodology: The study included 69 patients who received XELOX + bevacizumab therapy for advanced or recurrent colorectal cancer. In all the patients, oxaliplatin (130 mg/m 2 ) was administered in combination with DEX (6.6 mg) via the peripheral vein. Results: Vascular pain developed in 47 patients (68.1%), but it was transient. No patients required CV port implantation. Grade 3 or higher hemotoxicity was noted in 14.5% of the patients, and grade 3 or higher nonhematological toxicity was noted in 20.3% of the Research Article British Journal of Medicine & Medical Research, 2(2): 132-141, 2012 133 patients. The response rate was 59.4%. One patient experienced hypersensitivity reactions to oxaliplatin. Conclusions: The recorded response rate combined with the use of DEX suggests that DEX probably does not exert adverse effects on the therapy, ie, it does not affect the stability of oxaliplatin by elevating the pH. DEX may be useful not only for controlling vascular pain caused by the administration of oxaliplatin via the peripheral vein but also for controlling oxaliplatin-induced hypersensitivity reactions.

Dexamethasone as a Means Not Only for Controlling Vascular Pain Caused by the Administration of Oxaliplatin Via the Peripheral Vein But Also for Controlling Oxaliplatin-Induced Hypersensitivity Reactions

Dexamethasone as a Means Not Only for Controlling Vascular Pain Caused by the Administration of Oxaliplatin Via the Peripheral Vein But Also for Controlling Oxaliplatin-Induced Hypersensitivity Reactions

Risk Factors for Oxaliplatin-Induced Hypersensitivity Reactions in Japanese Patients with Advanced Colorectal Cancer

Previously, we suggested that oxaliplatin (L-OHP)-related grade 3/4 hypersensitivity reactions occurred immediately after the initiation, but grade 1/2 reactions did not. This study was conducted to clarify the risk factors for L-OHP-related hypersensitivity reactions. Clinical data from 108 Japanese patients with colorectal cancer were analyzed, who were treated with L-OHP-containing regimens, FOLFOX4 and/or mFOLFOX6. The risk factors examined included demographic data, preexisting allergies, laboratory test data, treatment regimen, treatment line of therapy, pretreatment with steroids, total number of cycles and cumulative amount of L-OHP. The incidence of grade 1/2 and grade 3/4 hypersensitivity reactions were found at 13.0% (14/108) and 9.3% (10/108), respectively. Female (P = 0.037), preexisting allergies (P = 0.004) and lower level of lactate dehydrogenase (P = 0.003) were risk factors for grade 1/2 hypersensitivity reactions, and higher neutrophil count (P = 0.043) and lower monocyte count (P = 0.007) were for grade 3/4 reactions. Total number of cycles were larger in the patients with grade 3/4 reactions than those without reactions (P = 0.049). Further extensive examination with a large number of patients is needed to establish a patient management strategy.