Dexrazoxane has been used successfully to reduce
cardiac toxicity in patients receiving
anthracycline-based
chemotherapy for
cancer (predominantly women with advanced
breast cancer). The
drug is thought to reduce the cardiotoxic effects of
anthracyclines by binding to free and bound
iron, thereby reducing the formation of
anthracycline-
iron complexes and the subsequent generation of
reactive oxygen species which are toxic to surrounding cardiac tissue. Clinical trials in women with advanced
breast cancer have found that patients given
dexrazoxane (about 30 minutes prior to
anthracycline therapy;
dexrazoxane to
doxorubicin dosage ratio 20:1 or 10:1) have a significantly lower overall incidence of
cardiac events than placebo recipients (14 or 15% vs 31%) when the
drug is initiated at the same time as
doxorubicin.
Cardiac events included
congestive heart failure (CHF), a significant reduction in left ventricular ejection fraction and/or a > or = 2-point increase in the Billingham biopsy score. These results are supported by the findings of studies which used control groups (patients who received only
chemotherapy) for comparison. The
drug appears to offer cardiac protection irrespective of pre-existing cardiac risk factors. In addition, cardiac protection has been shown in patients given the
drug after receiving a cumulative
doxorubicin dose > or = 300 mg/m2. It remains to be confirmed that
dexrazoxane does not affect the antitumour activity of
doxorubicin: although most studies found that clinical end-points (including tumour response rates, time to
disease progression and survival duration) did not differ significantly between treatment groups, the largest study did show a significant reduction in response rates in
dexrazoxane versus placebo recipients.
Dexrazoxane permits the administration of
doxorubicin beyond standard cumulative doses; however, it is unclear whether this will translate into prolonged survival. Preliminary results (from small nonblind studies) indicate that
dexrazoxane reduces
cardiac toxicity in children and adolescents receiving
anthracycline-based
therapy for a range of
malignancies. The long term benefits with regard to prevention of late-onset
cardiac toxicity remain unclear. With the exception of severe leucopenia [Eastern Cooperative Oncology Group (ECOG) grade 3/4 toxicity], the incidence of haematological and nonhaematological adverse events appears similar in patients given
dexrazoxane to that in placebo recipients undergoing
anthracycline-based
chemotherapy. Although preliminary pharmacoeconomic analyses have shown
dexrazoxane to be a cost-effective agent in women with advanced
breast cancer, they require confirmation.
CONCLUSIONS: