High-dose dexamethasone and prolonged infusion time prevent oxaliplatin-related hypersensitivity reactions in patients with metastatic colorectal cancer

BACKGROUND: Oxaliplatin (OXA), a key cytotoxic agent used in the treatment of gastrointestinal cancers, is frequently discontinued due to hypersensitivity reactions (HSRs). We developed a protocol to mitigate HSRs and assessed its clinical efficacy. METHODS: We retrospectively analyzed HSRs in patients with metastatic colorectal cancer (mCRC) who were treated with OXA-containing regimens between 2005 and 2019. We evaluated the clinical utility of our HSR prevention protocol in patients who experienced grade 1-3 HSRs following OXA-based chemotherapy. The protocol involved increasing dexamethasone to 16.5 mg/body and extending the OXA infusion time from 2 to 4 h. RESULTS: Among 205 patients, 105 (51.2%) experienced grade 1, 95 (46.3%) grade 2, and 5 (2.4%) grade 3 HSRs. Most patients (87.8%) received either the FOLFOX4 or modified FOLFOX6 regimen. Patients underwent a median of 11 OXA cycles before their initial HSR. OXA was successfully reintroduced in 108 patients (52.7%) using the HSR prevention protocol. The median OXA-free interval was 23 days and the median progression-free survival after reintroduction was 6.4 months (95% confidence interval [CI]: 4.6-8.2). Reasons for discontinuation included a second HSR in 97 patients (47.3%), disease progression in 74 (36.1%), and chemotherapy-induced peripheral neuropathy (CIPN) in 15 (7.3%). Forty-six patients (22.4%) experienced an HSR during the initial prevention protocol. Only six patients (2.9%) experienced grade 3 HSRs and no grade 4 or 5 events were observed. CONCLUSION: High-dose dexamethasone and prolonged infusion time may enable OXA reintroduction, providing an alternative to permanent discontinuation in mCRC patients with prior HSRs. REGISTRY NUMBER: 2024-GB-073 (retrospectively registered).