Utilization of Dexrazoxane in Patients Treated with Doxorubicin: A Retrospective, Propensity Matched Analysis of Cardiac Function and Toxicity

Zachary Neiman^1*Carlo Legasto²Alan Chin²Tiffany Guan²Brian Schulte^3,4

• ¹School of Medicine, University of California San Francisco, San Francisco, California, United States
• ²Department of Pharmaceutical Services, University of California San Francisco, San Francisco, United States
• ³Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, United States
• ⁴Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, United States

Introduction: Dexrazoxane (DZR) has been used to prevent cardiotoxicity from doxorubicin (DOX), particularly within the context of younger patients with cancer and those with known cardiac dysfunction. Herein, we sought to further qualify the role of DZR by evaluating its capacity to mitigate cardiotoxicity for patients actively receiving DOX, while also measuring concomitant toxicities.Materials and Methods: We utilized a retrospective propensity matched cohort design at a single academic center, comparing outcomes for patients treated with DZR in combination with DOX to patients who received DOX alone. Patients were matched by age, sex, and cumulative lifetime dose of DOX. Cardiotoxicity was measured as change in ejection fraction (EF) during and after treatment. To discern an association between DZR and other toxicities, we utilized Common Terminology Criteria for Adverse Events Version 5 (CTCAE).Results: 152 patients were studied between the two groups. The DOX alone and DOX + DZR groups had median ages of 36 and 28 (ranges 18-68 and 18-69) and median total cumulative DOX at 375 mg/m2 (ranges 75-525 and 75-600), respectively. Patients were followed up with their last measured EFs at -3 and 18.5 median days after their last DOX dose. The median change in EF for DOX alone was -2% and -0.7% for the DOX + DZR group (p = 0.9174). There were 16 and 41 patients with CTCAE grade 4 anemia in the DOX alone and DOX + DZR groups, respectively (p = 0.0002). There were 15 and 50 patients with grade 4 neutropenia, respectively (p = 0.0013).Discussion: The addition of DZR to DOX did not have a statistically significant impact on EF for patients during the treatment window. Recognizing the limitations of the dataset, this may indicate a lack of large immediate benefit to co-administration of DZR with DOX. There was an increased rate of higher-grade adverse events of neutropenia and anemia for patients receiving the combination, though this may be a consequence of confounding factors. Additional analysis is merited, ideally by means of larger multi-institutional or prospective studies.