A phase II study of intraperitoneal carboplatin as adjuvant treatment in early-stage ovarian cancer patients.

In a previously reported phase I study of carboplatin administered ip to patients with ovarian cancer at our clinic, it was determined that the recommended dose for phase II was 500 mg/m2. In this study, this dose was given to 47 patients with the purpose of determining the relapse-free interval and toxicity. Four courses were given with a 28-day interval in an escalated fashion. Median age of patients was 55 years. Karnofsky index was 100 in 98% of the patients. Thirty-one patients had FIGO stage I and 16 patients had FIGO stage II ovarian cancer. Median time to recurrence has not yet been reached among 43 evaluable patients after a median (range) follow-up time of 26.2 (5.5-45.9) months. Recurrent disease was documented in 10 patients (23%). The relapse site was intraabdominal in 7 and extraabdominal in 1 patient. Two patients had combined intra- and extraabdominal relapse sites. Thirty-six of 43 patients went through second-look surgery. The total number of treatment cycles given to evaluable patients was 154. In the patient group with relapsed tumor, > or = 3 courses were administered to 60%, whereas nonrelapsed patients had > or = 3 courses in 94% (P = 0.019). The reason for this distribution was higher toxicity and more frequent catheter-related problems in patients with relapsed tumor. Median (range) disease-free interval for relapsed patients was 11.5 (5.5-26.6) months. Myelosuppression, especially thrombocytopenia, was the dose-limiting systemic toxicity. The overall hematologic toxicity (all courses) was median (range) WBC 3.9(0.3-25.0) x 10(9)/liter, PLTC 212(7-961) x 10(9)/liter, and Hb 109(75-153) g/liter. WHO grade 4 toxicity for WBC was observed in 6.7%, for PLTC in 17.8%, and for Hb in 0% of the patients. Day to nadir values for WBC, PLTC, and HB were in median (cycle 1-4) 18, 16, and 18 days, respectively. Subjective toxicity was mild. In conclusion, ip carboplatin as a single-agent drug in first-line adjuvant chemotherapy of early-stage ovarian cancer has shown moderate activity. The administered dose in this study was safe, with acceptable toxicity.