Phase II study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma

Purpose: To determine the efficacy and toxicity of topotecan administered as a 5-day intravenous infusion in patients with advanced ovarian cancer refractory to cisplatin-based chemotherapy. Patients and Methods: Thirty patients with advanced epithelial ovarian cancer refractory to cisplatin- based chemotherapy received intravenous infusions of topotecan 1.5 mg/m² delivered over 30 minutes each day for 5 days. A course was repeated every 21 days. The patient eligibility requirements included age > 18 years, Zubrod score ≤ 2, measurable disease, adequate hepatic and renal function, neutrophil count ≥ 1,500/μL, platelet count ≥ 100,000/μL, and anticipated survival ≥ 3 months. Results: Twenty eight patients were assessable for response and toxicity. All Patients were assessable for survival. The major toxicity from administration of topotecan at this dose schedule was myelosuppression; 21 patients required dose reductions. Four patients had neutropenic fever that required hospitalization, and seven patients required platelet transfusions. Maculopapular pruritic exanthema occurred in 20% of patients; gastrointestinal side effects were mild. No deaths were reported on the study. At dose levels of 1.5, 1.25, and 1.0 mg/m², 61%, 31%, and 25% of patients, respectively, required dose reductions. Of 28 assessable patients, four (14%; 95% confidence interval [CI], 4% to 34%) achieved a partial response (PR) at a median of 1.4 months and lasting 8.9 months, and 17 had stable disease (SD). The overall median survival time was 10.0 months (95% CI, 8.1 to 13.5). Conclusion: Topotecan shows modest clinical activity against cisplatin-refractory ovarian cancer, although the dose-intensity is compromised by the depth of the granulocyte nadir and the duration of granulocytopenia. Further studies of topotecan may necessitate a reevaluation of optimal dose schedule, with the possible incorporation of multilineage cytokines, and its activity in taxane-resistant tumors.