Doxorubicin: alteration of dose scheduling as a means of reducing cardiotoxicity

The long-term therapeutic potential of doxorubicin is often limited by the predictable development of a dose-related cardiomyopathy. Empiric limitations of cumulative doses to 450-550 mg/m2 minimize the incidence of this potentially fatal toxicity. This review presents recent studies performed to examine the potential for altered dose schedule to reduce or delay this toxicity and maintain therapeutic efficacy. Altering doxorubicin's dosing schedule from the standard three-weekly regimen to a continuous infusion or weekly schedule has been shown to delay cardiotoxicity. Data presented suggest that doxorubicin administered on a weekly schedule significantly reduces cardiotoxicity as compared with a three-weekly schedule and allows approximately 160 mg/m2 more of the drug to be administered to reach the same level of cardiotoxicity as measured by endomyocardial biopsy. This corresponds clinically to two additional months of therapy. Cumulated response data suggest that continuous infusion or weekly schedules of doxorubicin are equally efficacious as the standard three-weekly schedule.