PD-008 Safety and efficacy of desensitization protocols for platinum hypersensitivity reactions

Abstract

Introduction: Platinum agents are commonly used in chemotherapeutic regimens for numerous gastrointestinal and gynecologic malignancies. Hypersensitivity reactions to oxaliplatin have been reported in up to 20% of patients receiving the drug, and desensitization protocols have been developed to allow its continued use. We sought to evaluate the safety and efficiency of established desensitization protocols by characterizing the frequency and severity of hypersensitivity reactions in patients undergoing desensitization.Methods: We identified all patients undergoing an in-hospital, nurse-monitored desensitization protocol for platinum hypersensitivity between 2010 and 2014 at Mayo Clinic, Rochester. The protocol was administered for all cycles subsequent to the hypersensitivity reaction. It was standard across all cases and involved pre-treatment with steroids, diphenhydramine, and famotidine, along with slowly escalated drug infusion rates administered in an inpatient non-ICU setting. Retrospective data was abstracted from electronic medical records, and all nurse- or physician-documented adverse events were recorded. Reactions were classified as severe when potentially life-threatening signs or symptoms were observed, such as chest pain, dyspnea, hypotension, or severe hypertension.Results: A total of 54 patients (20 oxaliplatin, 34 carboplatin) underwent chemotherapy desensitization. Diagnoses of hypersensitivity were based on clinical suspicion, and occurred after a median of 8 prior doses (range 2-20 for oxaliplatin, 1-24 carboplatin). On the desensitization protocol, oxaliplatin was given for a median of 2.5 cycles (range 1-7), and carboplatin was given a median of 4 (range 1-14) doses. During 54 oxaliplatin and 156 carboplatin desensitization episodes, 18.5% (oxaliplatin) and 13.5% (carboplatin) of cycles resulted in adverse reactions. Of these, only 1 (1.9%) oxaliplatin and 5 (3.2%) carboplatin episodes were severe. There were no deaths or ICU admissions. Oxaliplatin was more likely than carboplatin to generate a reaction on protocol, but no oxaliplatin reaction was noted after two desensitization cycles. On average, carboplatin patients received a greater number of desensitization cycles, but re-emerging reactions were recorded up to 5 cycles into the desensitization treatment. The majority of patients having one desensitization reaction did not have a subsequent one (oxaliplatin 5/6, carboplatin 9/13).Conclusion: Oxaliplatin is associated with a higher probability of having a hypersensitivity reaction than carboplatin on a desensitization protocol; however, the risk of reaction is low after the second desensitization cycle, making this group a potential target for de-escalation of therapy for subsequent cycles. The overall incidence of serious events was low, indicating that desensitization was effective and administration in an outpatient setting can be considered. Introduction: Platinum agents are commonly used in chemotherapeutic regimens for numerous gastrointestinal and gynecologic malignancies. Hypersensitivity reactions to oxaliplatin have been reported in up to 20% of patients receiving the drug, and desensitization protocols have been developed to allow its continued use. We sought to evaluate the safety and efficiency of established desensitization protocols by characterizing the frequency and severity of hypersensitivity reactions in patients undergoing desensitization. Methods: We identified all patients undergoing an in-hospital, nurse-monitored desensitization protocol for platinum hypersensitivity between 2010 and 2014 at Mayo Clinic, Rochester. The protocol was administered for all cycles subsequent to the hypersensitivity reaction. It was standard across all cases and involved pre-treatment with steroids, diphenhydramine, and famotidine, along with slowly escalated drug infusion rates administered in an inpatient non-ICU setting. Retrospective data was abstracted from electronic medical records, and all nurse- or physician-documented adverse events were recorded. Reactions were classified as severe when potentially life-threatening signs or symptoms were observed, such as chest pain, dyspnea, hypotension, or severe hypertension. Results: A total of 54 patients (20 oxaliplatin, 34 carboplatin) underwent chemotherapy desensitization. Diagnoses of hypersensitivity were based on clinical suspicion, and occurred after a median of 8 prior doses (range 2-20 for oxaliplatin, 1-24 carboplatin). On the desensitization protocol, oxaliplatin was given for a median of 2.5 cycles (range 1-7), and carboplatin was given a median of 4 (range 1-14) doses. During 54 oxaliplatin and 156 carboplatin desensitization episodes, 18.5% (oxaliplatin) and 13.5% (carboplatin) of cycles resulted in adverse reactions. Of these, only 1 (1.9%) oxaliplatin and 5 (3.2%) carboplatin episodes were severe. There were no deaths or ICU admissions. Oxaliplatin was more likely than carboplatin to generate a reaction on protocol, but no oxaliplatin reaction was noted after two desensitization cycles. On average, carboplatin patients received a greater number of desensitization cycles, but re-emerging reactions were recorded up to 5 cycles into the desensitization treatment. The majority of patients having one desensitization reaction did not have a subsequent one (oxaliplatin 5/6, carboplatin 9/13). Conclusion: Oxaliplatin is associated with a higher probability of having a hypersensitivity reaction than carboplatin on a desensitization protocol; however, the risk of reaction is low after the second desensitization cycle, making this group a potential target for de-escalation of therapy for subsequent cycles. The overall incidence of serious events was low, indicating that desensitization was effective and administration in an outpatient setting can be considered.