Phase II trial of gemcitabine plus cisplatin repeating doublet therapy in previously treated, relapsed ovarian cancer patients.

OBJECTIVES The aim was to determine the safety and efficacy of gemcitabine plus cisplatin for patients with relapsed ovarian carcinoma and to compare ex vivo drug sensitivity profiles with clinical outcomes. PATIENTS AND METHODS Previously treated patients with ovarian carcinoma received cisplatin (30 mg/m(2)) plus gemcitabine (600-750 mg/m(2)) on Days 1 and 8 of each 21-day cycle. Seventeen of the 27 patients underwent ex vivo analyses for correlation with clinical response. RESULTS Of 27 patients, there were 7 (26%) complete and 12 (44%) partial responses, for an overall response rate of 70% (95% CI: 53-87%). Toxicities included neutropenia Grade III in 51.9%, Grade IV in 29.6%; anemia Grade III in 18.5 %; thrombocytopenia Grade III in 66.7 %, Grade IV in 29.6%; nausea and vomiting Grade III in 14.8 %; peripheral neuropathy Grade III in 3.7%; and alopecia Grade IV in 11.1% of patients. The median time to progression for objective responders was 7.9 months with a range of 2.1 to 13.2 months. There were no treatment-related deaths. Ex vivo results correlated with response, time to progression, and survival, remaining significant when adjusted for platin-resistance and number of prior therapies. Adjustment for platin-free interval decreased the significance but did not, in and of itself, predict significantly for progression-free survival. CONCLUSIONS Cisplatin plus gemcitabine is active for patients with relapsed ovarian cancer. Toxicities, primarily hematologic, are manageable with dose modifications. Responses observed in heavily pretreated and platin-resistant patients indicate activity in drug-refractory patients. The results of the ex vivo analyses correlate with clinical outcomes.