Incidence, onset, severity, risk factors, and rechallenge strategies of etoposide infusion-related reactions in adults: A retrospective cohort study

Introduction The estimated incidence of etoposide infusion-related reactions (IRRs) in the general population is 1–3%, with pediatric reports ranging from 1–27.1%, and adult data being limited. Inconsistent documentation of IRR onset and underreporting of mild reactions have contributed to gaps in the literature. Rechallenging practices following infusion interruption are not standardized. This study aimed to evaluate the incidence, onset, severity, risk factors, and rechallenge strategies for etoposide IRRs in adults. Methods This retrospective cohort study included adult patients who initiated intravenous etoposide at Horizon Health Network in New Brunswick, Canada, between January 1, 2023, and June 30, 2025. Descriptive statistics were used to characterize IRR incidence, onset, severity, and rechallenge strategies. Demographic and treatment characteristics were compared between patients with and without IRRs using chi-square, Fisher's exact, and Mann-Whitney U tests. Results Among 199 identified patients, 29 experienced at least one etoposide IRR (14.6%), most commonly occurring during cycle 2 (51.7%), with grade 2 reactions (65.5%) predominating. No demographic or treatment-related factors were significantly associated with IRR occurrence. Rechallenge strategies primarily involved infusion rate reduction and addition of diphenhydramine, corticosteroids, and famotidine following first IRRs. Switching to etoposide phosphate was more generally reserved for second IRRs. Conclusion The incidence of etoposide IRRs in adults was higher than previously reported. Reactions may occur beyond initial infusions and can recur. Although no clear risk factors were identified, rechallenge strategies were generally successful and allowed for continuation of therapy following infusion interruptions.