Ameliorating anthracycline cardiotoxicity in children with cancer: clinical trials with dexrazoxane

Anthracyclines have major activity against a broad range of childhood cancers. Concern over the risk of long-term cardiotoxicity associated with their use has called into question the role of these agents in the frontline treatment of many patients. Dexrazoxane was developed as a specific cardioprotectant "antidote" which can prevent anthracycline cardiotoxicity without inhibiting its antitumor effect. To date, four clinical trials of dexrazoxane have been conducted in pediatric cancer patients (primarily with sarcomas). The two largest series, conducted at the National Cancer Institute Pediatric Branch, demonstrated significant short-term cardioprotection with no evidence of interference with antitumor activity. Additional clinical trials are ongoing, or planned to open shortly, to better evaluate the role of dexrazoxane in the treatment of childhood cancer. These studies, being conducted on larger numbers of patients with better prospects for cure, are expected to definitviely answer the outstanding questions of whether preventing short-term, subclinical cardiotoxicity will translate into long-term cardioprotection, and whether the use of dexrazoxane interferes with the anti-tumor efficacy of doxorubicin-containing regimens.