Alternate Dosing Schedules for Topotecan in the Treatment of Recurrent Ovarian Cancer

Abstract

Topotecan has demonstrated efficacy in the treatment of both platinum-sensitive and platinum-resistant recurrent ovarian cancer. However, the optimal dosing for topotecan has not been established. The standard dosing regimen is 1.5 mg/m(2)/day on days 1-5 of a 21-day cycle, with response rates ranging from 13%-33%. Although the resulting hematologic toxicities are reversible and noncumulative, this schedule is associated with significant myelosuppression. Ongoing clinical phase I and II trials have evaluated alternative dosing schedules such as the 21-day 24-hour continuous intravenous (c.i.v.), the 3-day i.v. bolus, the weekly 72-hour c.i.v., the weekly 24-hour c.i.v., and the weekly bolus i.v. regimens. Prolonged exposure to topotecan has been shown to increase the efficacy of topotecan, whereas shorter regimens decrease exposure to the drug and therefore decrease toxicity. Preliminary studies investigating the weekly bolus i.v. regimen have demonstrated response rates comparable with those achieved with the standard dosing regimen, with a lower frequency of severe toxicity. Although randomized, controlled comparative trials are necessary to determine relative efficacy, results from studies utilizing other alternative regimens are less encouraging, especially for lower-risk patients with platinum-sensitive ovarian cancer who are likely to tolerate higher doses of topotecan. Optimizing the dosing regimen will also increase the quality of life for the patient through increased efficacy, decreased toxicity, and increased convenience of administration. Continued investigation of the weekly i.v. bolus is needed to fully elucidate the contribution of this regimen to the current armamentarium used in the treatment of patients with relapsed ovarian cancer