Oxaliplatin Desensitization Research Articles

Prevention of allergic reactions during oxaliplatin desensitization through inhibition of Bruton tyrosine kinase

BackgroundAcute infusion reactions to oxaliplatin, a chemotherapeutic used to treat gastrointestinal cancers, are observed in about 20% of patients. Rapid drug desensitization (RDD) protocols often allow the continuation of oxaliplatin in patients with no alternative options. Break-through symptoms including anaphylaxis can still occur during RDDs. ObjectiveTo evaluate if pretreatment with acalabrutinib, a Bruton’s tyrosine kinase inhibitor, can prevent anaphylaxis during a RDD in a patient sensitized to oxaliplatin. MethodsA 52-year-old male with locally advanced gastric carcinoma developed anaphylaxis during his 5th cycle of oxaliplatin. As he required 6 additional cycles to complete his curative-intent treatment regimen, he underwent RDD to oxaliplatin but still developed severe acute reactions. The risks and benefits of adding acalabrutinib prior to and during a RDD, were reviewed and he elected to proceed. ResultsWith acalabrutinib taken prior to and during the RDD, the patient was able to tolerate oxaliplatin RDDs without complication. Consistent with its mechanism of action, acalabrutinib completely blocked the patient’s positive skin prick response to oxaliplatin. Acalabrutinib did not alter the percentage of circulating basophils (1.24% versus 0.98%) prior to the RDD but protected from basopenia (0.74% versus 0.09%) after the RDD. Acalabrutinib was associated with a drastic reduction in the ability of basophils to upregulate CD63 in vitro following incubation with oxaliplatin (0.11% versus 2.38%) or polyclonal anti-human IgE antibody (0.08% versus 44.2%). ConclusionsFive doses of acalabrutinib 100mg orally twice daily starting the evening 2 days before and continuing through a RDD allowed a sensitized patient to successfully and safely receive oxaliplatin.

Oxaliplatin desensitization in patients with GI malignancies: Experience from a tertiary cancer center.

89 Background: Oxaliplatin hypersensitivity is not uncommon in patients with gastrointestinal (GI) cancers receiving chemotherapy. The use of oral premeditations (dexamethasone, cetirizine and famotidine) starting 24 hours before treatment and continuing for a total of three days, further intravenous premedication (dexamethasone, chlorphenamine and famotidine) 30 minutes before treatment and the gradual administration of oxaliplatin over 6.5 hours in four separate escalating doses (desensitisation protocol) is commonly used in such cases. While desensitisation is an option, especially in severe cases, responses and survival outcomes upon rechallenge are not well described. Methods: A retrospective chart review of patients with various GI malignancies who received oxaliplatin-based desensitisation chemotherapy after a severe drug reaction between October 2019 and October 2022 at a single cancer centre was performed. Clinicopathological characteristics and oncological outcomes were assessed. Results: Forty-four patients with a median age of 61 years (range 38-81) were studied. The majority had a diagnosis of CRC (n=22; 50%), followed by oesophago-gastric (n=19; 4%), appendiceal (n=1), cholangiocarcinoma (n=1), and cancer of unknown primary (n=1). More than two thirds of patients (n=32, 73%) were treated with palliative intent. The most common regimens associated with oxaliplatin hypersensitivity reactions after a median of 3 cycles (range 1-10) were FOLFOX (n=24, 55%), CAPOX (n=18, 41%), FLOT (n=1) and FOLFOXIRI (n=1). Seven patients (16%) had another reaction after desensitisation, leading to discontinuation of treatment. Thirty-seven patients (84%) completed treatment as planned. Treatment outcomes after desensitisation included 5 (11%) patients with no evidence of disease (NED) after adjuvant treatment, 16 (37%) patients with disease control, including 3 (7%) partial responders (PR) and 13 (30%) patients with stable disease (SD), and 23 (52%) patients with progressive disease (PD). Conclusions: Oxaliplatin desensitisation is feasible with low discontinuation rates and leads to acceptable oncological outcomes. All patients should be offered desensitisation to allow continuation of active systemic therapy.

Kounis Syndrome During an Oxaliplatin Desensitization Protocol.

Kounis Syndrome During an Oxaliplatin Desensitization Protocol.

P24-3 Oxaliplatin desensitization therapy in patients with colorectal cancer

P24-3 Oxaliplatin desensitization therapy in patients with colorectal cancer

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.

P-199 Oxaliplatin desensitization in coloretal cancer: A way to prolong effective treatments

P-199 Oxaliplatin desensitization in coloretal cancer: A way to prolong effective treatments

Screening for drug-dependent antibodies to prevent complications in patients receiving oxaliplatin desensitization

Oxaliplatin-induced immune thrombocytopenia (OIIT), which is caused by antibodies that target platelets in the presence of oxaliplatin, is a rare complication of repeated oxaliplatin exposure and oxaliplatin desensitization with high morbidity (bleeding with refractory thrombocytopenia, autoimmune hemolytic anemia in certain patients, and even renal failure in patients with thrombotic microangiopathy). We sought to prevent OIIT complications in patients receiving oxaliplatin desensitization through screening selected patients for drug-dependent antibodies prior to the onset of clinical complications.

A case report of an adverse drug reaction with a combination of oxaliplatin and perindopril

Introduction: Oxaliplatin is a third-generation platinum compound that is used as a single agent and in combination with fluorouracil (5-FU) to treat a variety of solid organ cancers. Patients treated with Oxaliplatin may develop hypersensitivity reactions. Angiotensin-converting enzyme inhibitors (ACEI) are established to have multiple cardiovascular benefits. Recent studies also suggest that ACEI may have a role in preventing Oxaliplatin-induced peripheral neuropathy. Case Report: We present a case of a patient who presented with adverse reactions on two separate occasions. At the time of the first reaction he had been on an ACEI (Perindopril), which he had used for four years for management of hypertension and was within hours of receiving the seventh cycle of adjuvant modified Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX-6) for ypT3N0 rectal adenocarcinoma. On the second episode, he presented with a reaction before his eighth cycle of chemotherapy, while still taking the ACEI. Determination of the cause of the reactions was challenging and management involved switching from Perindopril to a calcium channel blocker (Amlodipine) and Oxaliplatin desensitization. The patient was able to complete chemotherapy treatment with no further reactions. Conclusion: The combination of Perindopril with Oxaliplatin could increase the risk of adverse reactions. These adverse reactions could be managed by substituting Perindopril with a calcium channel blocker and use of an Oxaliplatin desensitization protocol.

A Novel Oxaliplatin Desensitization Protocol: Short, Safe, and Effective

A Novel Oxaliplatin Desensitization Protocol: Short, Safe, and Effective

Analysis and treatment of 45 platinum-allergic gynecologic malignant tumors.

This study aimed to explore the potential risk factors of platinum allergy and follow-up treatment to provide a reference for the clinical prevention and treatment of platinum allergic reactions in patients with gynecological tumors. The study retrospectively analyzed 45 cases of platinum allergic reactions that occurred in Shengjing Hospital affiliated to China Medical University from August 2010 to July 2016. Analysis of risk factors included the cumulative dose, treatment course and time intervals. The cumulative carboplatin dose in allergic patients ranged from 900 to 10250mg (average 4845mg). The 45 allergic reactions occurred between the 3rd and 25th course of treatment (average 11.4 courses). The average re-treatment interval of carboplatin-allergic patients was 28.1 months, including 93.3% of patients with platinum re-treatment interval of more than 1year. The allergic reaction occurred in the 2nd or 3rd course of re-treatment in 26 patients, accounting for 70.3% of all patients with recurrence. Seventeen patients were subjected to desensitization therapy, among which 13 cases were well tolerated. Patients who received more than 8 courses of carboplatin or a cumulative dose of more than 3500mg were the high-risk population for platinum allergy. The 2nd and 3rd treatment course after restarting carboplatin treatment after an interval time of more than 1year was the high incident period of carboplatin allergy. Skin tests should be conducted in patients with high risk of carboplatin allergy. In cases of carboplatin allergy, patients could receive carboplatin or oxaliplatin desensitization therapy.

Oxaliplatin desensitization after hypersensitivity reaction: A single-center experience on more than 300 procedures.

610 Background: Oxaliplatin is an essential drug in gastrointestinal oncology. Hypersensitivity reactions (HSR) occur frequently (incidence varying from 10% to 25%), leading to permanent treatment discontinuation. The present study aimed to report our experience of oxaliplatin desensitization in patients with history of HSR to oxaliplatin. Methods: We retrospectively reviewed all patients who received at least one infusion of oxaliplatin according to a desensitization protocol after prior history of HSR to oxaliplatin, from June 2011 until June 2017. HSRs were classified from NCI CTC-AE grade 1 (transient rash, fever < 38°C) to grade 4 (anaphylaxis). We applied in all cases a desensitization protocol in which the oxaliplatin infusion rate is gradually increased from 1mL/hr. to 150mL/hr., on an inpatient basis. Intravenous or hepatic arterial infusion was used depending on clinical setting. Results: Overall, 54 patients were included in this study, in whom HSR to oxaliplatin occurred after a median of 9 infusions (range, 1-31). The severity of HSRs was grade 1-2 in 33 patients (61%) and grade 3-4 in 21 patients (39%). A total of 305 oxaliplatin infusions according to a desensitization protocol were performed in these 54 patients (median, 5 infusions; range, 1-20). These infusions were by intravenous route in 42 patients (78%), by hepatic arterial route in 11 patients (18%), and both in 2 patients (4%). Infusions were well tolerated in 41 patients (76%), without new HSR. The remaining 13 patients (24%) experienced HSR recurrence (grade 2, 9 patients [69%]; grade 3, 4 patients [31%]). No anaphylaxis or oxaliplatin-related death occurred. In the 21 patients with a prior history of severe (grade 3-4) HSR, oxaliplatin desensitization procedure was effective and sustained in 16 patients (79%). Among 32 evaluable patients, 23 (72%) experienced disease control (14 partial responses, 9 stable diseases). Conclusions: Rechallenging Oxaliplatin desensitization procedure was successful in three out of four patients with prior history of HSR to oxaliplatin. Our retrospective study confirms that oxaliplatin desensitization is safe, and allows patients who developed HSR to continue an effective treatment.

Hypersensitivity Reactions to Oxaliplatin: Identifying the Risk Factors and Judging the Efficacy of a Desensitization Protocol

PurposeWe examined the clinical data of patients treated with oxaliplatin to determine the risk factors of oxaliplatin-related hypersensitivity reaction (HSR). In addition, we evaluated the efficacy of rechallenging patients with HSRs with oxaliplatin using prophylactic agents or desensitization procedures. MethodsThis study consisted of 162 patients with colorectal cancer (88 men and 74 women) who were treated consecutively at the outpatient chemotherapy department at University Hospital, Kyoto Prefectural University of Medicine. Patients underwent chemotherapy, including oxaliplatin, between March 2006 and June 2012. We analyzed the patients’ clinical backgrounds (eg, age, sex, performance status, disease stage, and allergic history) to uncover any connections to the development of HSR to oxaliplatin. In addition, we rechallenged 10 patients who had oxaliplatin-related HSR using prophylactic agents or desensitization procedures. FindingsOf 162 patients, 28 (17.2%) developed oxaliplatin-related HSRs (16, 2, 9 and 1 patient had grade 1, 2, 3, and 4 HSRs, respectively). The total cumulative dose of oxaliplatin at the onset of the HSR was 301 to 1126 mg/m2 (median, 582 mg/m2), and the first reactions developed in these patients after 5 to 17 infusions of oxaliplatin (median, 8 infusions). Logistic regression analysis indicated that sex (male: odds ratio = 3.624; 95% CI, 1.181–11.122; P = 0.024) and eosinophil count in peripheral blood (odds ratio = 35.118; 95% CI, 1.058–1166.007; P = 0.046) were independent variables for oxaliplatin-related HSRs. Rechallenging patients with prophylactic agents was successful in 2 (28.6%) of 7 patients who successfully completed their treatment. On the other hand, all 3 patients rechallenged with oxaliplatin using a desensitization protocol successfully completed their treatment without new HSRs. ImplicationsIn this retrospective study, we observed that being male and having higher counts of peripheral eosinophil could be predictors for HSR to oxaliplatin. In addition, this study confirms that oxaliplatin desensitization protocol allows patients who developed HSRs to continue with their treatment. However, the optimum desensitization protocol for oxaliplatin administration in terms of tolerability and efficacy needs to be defined.

Breakthrough Reactions during Oxaliplatin Desensitization: An Analysis of 177 Cases

Breakthrough Reactions during Oxaliplatin Desensitization: An Analysis of 177 Cases

Clinical Experience With Oxaliplatin (O) Desensitization (OD): A Case Series

Clinical Experience With Oxaliplatin (O) Desensitization (OD): A Case Series

Effectiveness of oxaliplatin desensitization protocols

Hypersensitivity reaction (HSR) to antineoplastic drugs can force doctors to stop treatment and seek other alternatives. These alternatives may be less effective, not as well tolerated and/or more expensive. Another option is to use desensitization protocols that induce a temporary state of tolerance by gradually administering small quantities of the antineoplastic drug until the therapeutic dosage is reached. The aim of this study is to assess the effectiveness of oxaliplatin desensitization protocols. A retrospective observational study was carried out between January 2006 and May 2011. The inclusion criteria were patients undergoing chemotherapy treatment with oxaliplatin who had developed an HSR to the drug and who were candidates for continuing the treatment using a desensitization protocol. The patients' clinical records were reviewed and variables were gathered relating to the patient, the treatment, the HSR, and the desensitization protocol administered. The data were analysed using version 18.0 of the statistics program SPSS. A total of 53 desensitization protocols were administered to 21 patients. In 89 % of these cases, no new reactions occurred while the drug was being administered. New reactions of mild severity only occurred in 11 % of cases, and none of these reactions were severe enough for treatment to be stopped. All patients were able to complete the desensitization protocol. This study confirms that oxaliplatin desensitization protocols are safe and effective and allow patients to continue with the treatment that initially caused an HSR.

Desensitization to oxaliplatin with two stages of premedication in a patient with metastatic rectal cancer

Oxaliplatin is a therapeutic platinum compound used for the treatment of colorectal cancer; however, it might induce hypersensitivity reactions, a critical situation that requires discontinuation of chemotherapies that contain oxaliplatin. Independent attempts of oxaliplatin desensitization have been reported, with mostly successful results. This letter reports a 53-year-old Japanese woman (weight, 70 kg) with chemorefractory metastatic rectal cancer who had undergone surgical intervention twice and received 3 treatment regimens. The patient developed grade 3 hypersensitivities to oxaliplatin during cumulative cycles of the FOLFOX (5-fluorouracil/leucovorin/oxaliplatin)-4 regimen. After the subsequent regimen failed, she was desensitized using a protocol of an 8-hour series of diluted-oxaliplatin infusions. Because, according to previously published desensitization reports, hypersensitivity reactions might recur during the final bag infusion of oxaliplatin despite intensive premedication, prophylactic antiemesis, corticosteroids, and antihistamines were administered twice (ie, before and during the oxaliplatin infusion). Allergic reactions were successfully and efficiently prevented with the 2 stages of intensive premedication in this patient who was able to receive oxaliplatin and had stabilized lung metastases. She was able to undergo desensitization for 5 cycles until acute development of obstructive pneumonia. In this report of a previously sensitized patient, a type I hypersensitivity reaction was successfully circumvented with 2-staged premedication for oxaliplatin desensitization. The optimum desensitization protocol for oxaliplatin administration in terms of efficacy and tolerability still needs to be defined.

Oxaliplatin (Ox) desensitization in colorectal cancer (CRC) patients: A single institution experience

15047 Background: Reported incidence of Ox hypersensitivity is 12–16%(Brandi G et al. Hypersensitivity reactions to oxaliplatin. Br J Cancer 2003; 89:477–81.). Ox is one of the most active agents i...

Successful desensitization protocol for hypersensitivity reactions caused by oxaliplatin

To report the successful desensitization of a patient with a hypersensitivity reaction to oxaliplatin. A 57-year-old woman with metastatic colon cancer was receiving oxaliplatin, fluorouracil and leucovorin every 2 weeks and showed a partial response to therapy. During the fourth cycle, an anaphylactic reaction with palpitations and rash occurred. The patient was hypotensive with mild pulmonary wheezing. Since oxaliplatin was the probable cause of the hypersensitivity reaction, therapy with this drug was discontinued. Therapy in the patient was continued using cetuximab and irinotecan but this resulted in progression of the cancer. In view of the initial satisfactory response to the oxaliplatin-based regimen, it was decided to attempt desensitization to oxaliplatin using a protocol adapted from carboplatin regimens. The desensitization procedure was successful and the patient subsequently tolerated an additional three cycles using this regimen without further symptoms of hypersensitivity. In cases with moderate-to-severe reactions to oxaliplatin, reexposure is not usually considered. However, a need to use first-line therapy when there is recurrence of the cancer has encouraged the development of rapid desensitization procedures which allow patients to be treated with medications to which they have previously shown hypersensitivity reactions. A combination of premedication using intravenous dexamethasone and a desensitization regimen was designed which was used successfully to increase concentrations and flow rates of oxaliplatin. Hypersensitivity reactions to oxaliplatin are not rare and physicians need to be aware of these. When substitution of another antineoplastic drug is not feasible, oxaliplatin desensitization should be considered even when hypersensitivity reactions to oxaliplatin are severe.

Successful desensitization to oxaliplatin with incorporation of calcium gluconate and magnesium sulfate

Since the results of the MOSAIC trial demonstrated an improved disease-free survival in stage III colorectal patients treated with oxaliplatin combined with 5-fluorouracil and folinic acid when they were compared with those treated with 5-fluorouracil and folinic acid alone, the addition of this organoplatin to 5-fluorouracil and folinic acid has become first-line adjuvant treatment for stage III colorectal cancer. Unfortunately, there is a small population of patients who develop grade III/IV hypersensitivity reactions to oxaliplatin which, until recently, have interfered with further treatment with oxaliplatin-containing regimens. Successful oxaliplatin desensitization protocols for patients having severe oxaliplatin hypersensitivity reactions have been reported. However, none of these protocols, have incorporated magnesium and calcium salts. Retrospective data has suggested that pretreating colorectal cancer patients with magnesium sulfate and calcium gluconate before the administration of oxaliplatin may reduce the incidence of neurotoxicities induced by this drug. Therefore, we modified a previously published oxaliplatin-desensitization protocol by incorporating intravenous calcium gluconate and magnesium sulfate, and report a patient with stage IIIc colorectal cancer and prior severe hypersensitivity reactions to oxaliplatin who underwent successful oxaliplatin desensitization using this protocol.

Anaphylactic Shock to Oxaliplatin in the Adjuvant Context

Objective: To report a case of anaphylactic shock in a patient receiving oxaliplatin treatment. Case Summary: A 60-year-old Chinese woman received adjuvant oxaliplatin in combination with fluorouracil and folinic acid for treatment of stage 3 colon cancer. Shortly after initiation of her 12th infusion, she developed anaphylactic shock. She has since fully recovered from the adverse drug event. She was not rechallenged with oxaliplatin. Discussion: Severe hypersensitivity reactions to oxaliplatin are rare. An objective causality assessment using the Naranjo probability scale revealed that an adverse drug reaction to oxaliplatin was highly probable. Based on the Common Terminology Criteria for Adverse Events version 3 for defining reaction severity, our patient had experienced a grade 4 reaction, or anaphylaxis. Conclusions: With more widespread use of oxaliplatin in the treatment of early stage as well as advanced disease, the potential for more instances of severe hypersensitivity reactions exists, although the percentage of grade 4 reactions will likely remain rare. The role of intradermal skin testing to predict oxaliplatin sensitivity and the implementation of oxaliplatin desensitization protocols in cases of severe hypersensitivity reactions to this drug in the adjuvant setting may be useful.