Late health outcomes after dexrazoxane treatment: A report from the Children's Oncology Group

BACKGROUND: The objective of this study was to examine long-term outcomes among children newly diagnosed with cancer who were treated in dexrazoxane-containing clinical trials. METHODS: P9404 (acute lymphoblastic leukemia/lymphoma ALL), P9425 and P9426 (Hodgkin lymphoma), P9754 (osteosarcoma), and Dana-Farber Cancer Institute 95-01 (ALL) enrolled 1308 patients between 1996 and 2001: 1066 were randomized (1:1) to doxorubicin with or without dexrazoxane, and 242 (from P9754) were nonrandomly assigned to receive dexrazoxane. Trial data were linked with the National Death Index, the Organ Procurement and Transplantation Network, the Pediatric Health Information System (PHIS), and Medicaid. Osteosarcoma survivors from the Childhood Cancer Survivor Study (CCSS; n = 495; no dexrazoxane) served as comparators in subanalyses. Follow-up events were assessed with cumulative incidence, Cox regression, and Fine-Gray methods. RESULTS: ) was 1.6% (vs 0% in P9754; P = .13). Among randomized patients, serious cardiovascular outcomes (cardiomyopathy, ischemic heart disease, and stroke) ascertained by PHIS/Medicaid occurred less commonly with dexrazoxane (5.6%) than without it (17.6%; P = .02), although cardiomyopathy rates alone did not differ (4.4% vs 8.1%; P = .35). CONCLUSIONS: Dexrazoxane did not appear to adversely affect long-term mortality, event-free survival, or second cancer risk.