Combined cisplatin and carboplatin chemotherapy for treatment of advanced epithelial ovarian cancer

Abstract

Purpose: The primary goal of this trial was to evaluate the clinical activity and the toxicity of a combination of cisplatin and carboplatin for women with advanced-stage epithelial ovarian cancer.

Patients and methods: Fifty-one consecutive evaluable patients with untreated stage III and IV epithelial ovarian cancer received 360 mg/m2 carboplatin on Day 1 and 50 mg/m2 cisplatin on Day 2 administered intravenously every 28 days for six cycles. Drug doses were adjusted for hematologic toxicity based on nadir counts during the prior therapy course. Dose levels included 300-400 mg/m2 carboplatin and 50-75 mg/m2 cisplatin. Second-look surgery was optional. Endpoints were clinical response, surgical response, progression-free survival, and survival.

Results: Of 8 patients with measurable disease, 3 (37.5%) had a clinical compete response, and 3 (37.5%) had a clinical partial response, for an overall clinical response rate of 75%. Of 39 patients who began chemotherapy with abnormal serum levels of CA 125, 31 (79%) achieved normalization of CA 125 at the completion of chemotherapy. Thirteen patients underwent second-look laparotomy. Of these, 7 (54%) had a pathological compete response, and 2 (15%) had a partial response. The median progression-free survival was 14 months, and the overall median survival was 32.5 months. Neutropenia and thrombocytopenia were the main dose-limiting toxicities. In addition, 9 patients developed grade 2 and 3 developed grade 3 ototoxicity.

Conclusion: This regimen is very active against advanced-stage epithelial ovarian cancer. The degree of ototoxicity observed is worrisome, but such toxicity may be ameliorated by limiting the dose of cisplatin and increasing the dose of carboplatin.