Use of ICRF-187 for Prevention of Anthracycline Cardiotoxicity in Children: Preliminary Results

Abstract

The objective of this study is to assess the efficacy of ICRF-187 as a protective agent against anthracycline cardiotoxicity. Cardiac function was evaluated by echocardiography before and after each cycle of anthracycline chemotherapy associated with ICRF-187 and compared with that of a second group receiving anthracycline chemotherapy without ICRF-187. The patients were a group of 15 consecutive children affected with various types of solid tumors who were treated with either doxorubicin-daunomycin or epirubicin (average doses 340 and 280 mg/m2, respectively), and treatment was associated with ICRF-187. A second group of 15 consecutive children affected with different malignancies were simultaneously treated with either doxorubicin-daunomycin or epirubicin (average doses 309 and 270 mg/m2, respectively), but without ICRF-187 association. None of the patients treated with anthracyclines and ICRF-187 association showed abnormalities on echocardiographic examination. In the second group of patients treated with anthracyclines but without ICRF-187 association, we observed a decrease in the left ventricular ejection fraction to < 55% and a decrease in the left ventricular fractional shortening to < 28% in two patients (13.3%). One of these (6.6%) showed a dilatative cardiomyopathy. Both groups of patients were treated with low doses of anthracyclines. Although this study was not randomized, in patients without ICRF-87 cardioprotection, there was a trend for a worse evolution with one case of clinical cardiomyopathy as well as subclinical cardiac abnormalities.

Cytoprotection in the treatment of pediatric cancer: Review of current strategies in adults and their application to children

“…In addition, left ventricular shortening fraction (LVSF) fell by a mean of 1% in the dexrazoxane group compared with 11% in the control group [99]. Similar results were obtained in a recent nonrandomized trial of 30 pediatric patients [100]. In a larger randomized trial of 39 pediatric patients with soft tissue sarcoma treated with doxorubicin, vincristine, and cyclophosphamide plus mesna, 20 patients received dexrazoxane at a dose 20-fold that of the anthracycline dose.…”

The current and future role of dexrazoxane as a cardioprotectant in anthracycline treatment: expert�panel�review

“…For instance, Wexler et al (Wexler et al 1996) reported 67% subclinical cardiotoxicity in control pediatric patients treated with doxorubicin, but only 22% in patients treated with doxorubicin and dexrazoxane. Pediatric studies with dexrazoxane have included patients with Ewing's sarcoma or related diseases (Wexler et al 1996), leukemia (Lipshultz et al 2002), osteosarcoma (Rubio et al 1995), and various mixed groups such as hepatoblastoma, Wilms tumor, non-Hodgkin lymphoma, and neuroblastoma (Bu'Lock et al 1993;Schiavetti et al 1997).…”

Long-term serial echocardiographic examination of late anthracycline cardiotoxicity and its prevention by dexrazoxane in paediatric patients

“…Dexrazoxane seems to be the most effective of these blocking agents [10,28,41]. Clinical trials of dexrazoxane have been conducted in children and an encouraging short-term cardioprotective effect with no evidence of interference with anti-tumour activity has been demonstrated using standard echocardiographic parameters of systolic function [4,27,30,40]. More recently, Lipshultz et al [24] have shown that dexrazoxane prevents or reduces cardiac injury, as reflected by elevation in troponin T, in paediatric patients treated with doxorubicin for childhood acute lymphoblastic leukaemia without compromising the anti-leukaemic efficacy.…”