Objective. Topotecan and carboplatin are active in relapsed ovarian cancer, but attempts to combine these agents are limited by myelotoxicity. This phase I/II trial combined weekly topotecan, which is less myelosuppressive than the standard 5-day regimen, with carboplatin in patients with potentially platinum-sensitive relapsed ovarian or peritoneal carcinoma (PS-OVCa/PCa). Methods. Eligible patients had PS-OVCa/PCa, performance status 0-2, and normal bone marrow, renal, and hepatic functions. On day 1 of a 21-day cycle, patients received carboplatin (area under the curve [AUC] 5) followed by topotecan 2.0 mg/m2, both via 30-min intravenous infusion. Topotecan 2.0 mg/m2 also was administered on days 8 and 15. Treatment was withheld for neutropenia or thrombocytopenia on day 8 or 15. Dose escalation was planned. Results. Seventeen patients received a total of 115 (median, 6)-cycles of chemotherapy. With carboplatin AUC 4, neutropenia prevented dose escalation of topotecan; hematologic toxicity caused 34/105 (32%) weekly treatments to be withheld. However, carboplatin could be dose escalated to AUC 5 when the day 15 dose of topotecan was withheld. In the intent-to-treat population, there were 4 (24%) complete and 9 (53%) partial responses, 2 (12%) patients (at the carboplatin AUC 4 dose) with stable disease, and 2 (12%) nonevaluable patients. Conclusion. Carboplatin (AUC 5) on day 1 in combination with topotecan 2.0 mg/m2 on days 1 and 8 of a 21-day cycle is well tolerated and active in patients with PS-OVCa/PCa. A phase II trial comparing this with other carboplatin therapeutic doublets in patients with recurrent ovarian cancer is warranted.
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