RANDOMIZED TRIAL OF THE CARDIOPROTECTIVE AGENT ICRF-187 IN PEDIATRIC SARCOMA PATIENTS TREATED WITH DOXORUBICIN

Purpose: We conducted an open-label, randomized trial to determine whe ther ICRF-187 would reduce doxorubicin-induced cardiotoxicity in pedia tric sarcoma patients. Methods: Thirty-eight patients were randomized to receive doxorubicin-containing chemotherapy (given as an intravenou s bolus) with or without ICRF-187, Resting left ventricular ejection f raction (LVEF) was monitored serially with multigated radionuclide ang iography (MUGA) scan, The two groups were compared for incidence and d egree of cardiotoxicity, response rates to four cycles of chemotherapy , event-free and overall survival, and incidence and severity of nonca rdiac toxicities. Results: Eighteen ICRF-187-treated and 15 control pa tients were assessable for cardiac toxicity, ICRF-187-treated patients were less likely to develop subclinical cardiotoxicity (22% v 67%, P< .01), had a smaller decline in LVEF per 100 mg/m(2) of doxorubicin (1, 0 v 2.7 percentage points, P=.02), and received a higher median cumula tive dose of doxorubicin (410 v 310 mg/m(2), P<.05) than did control p atients, Objective response rates were identical in the two groups, wi th no significant differences seen in event-free or overall survival, ICRF-187-treated patients had a significantly higher incidence of tran sient grade 1 serum transaminase elevations and a trend toward increas ed hematologic toxicity. Conclusion: ICRF-187 reduces the risk of deve loping short-term subclinical cardiotoxicity in pediatric sarcoma pati ents who receive vp to 410 mg/m(2) of doxorubicin, Response rates to c hemotherapy, event-free and overall survival, and noncardiac toxicitie s appear to be unaffected by the use of ICRF-187, Additional clinical trials with larger numbers of patients are needed to determine if the short-term cardioprotection afforded by ICRF-187 will reduce the incid ence of late cardiac complications in long-term survivors of childhood cancer.