Weekly topotecan in the management of ovarian cancer

Topotecan is an established treatment for patients with relapsed ovarian cancer, with good antitumor activity in both platinum-sensitive and -resistant disease. However, the perception of dose-limiting myelosuppression may have limited its use. Myelosuppression with topotecan is noncumulative, reversible, and predictable and as such can be successfully managed. Dose reductions and/or delays in patients at elevated risk, for example, patients with preexisting bone marrow damage from earlier treatment and those with diminished creatinine clearance, are usually effective in preventing complications. Most patients recover without incident and the requirement for specific therapy is generally low. The therapeutic index of topotecan may be improved by its use at first relapse, when patients have sustained less bone marrow damage. Alternative dosing schedules also show promise. Preclinical data suggest that repeated exposure to topotecan may be as effective as prolonged exposure, supporting the idea of weekly dosing. Phase I/II studies have confirmed that weekly topotecan dosing, using either a 24-h or a 30-min intravenous infusion, produces substantially less myelosuppression than the standard schedule (1.5 mg/m(2) daily for 5 days every 21 days). Early results indicate that antitumor activity is maintained, although further data are required to confirm this. Weekly administration of topotecan is an exciting new therapeutic option in the treatment of relapsed ovarian cancer.