Pilot evaluation of high-dose carboplatin and paclitaxel followed by high-dose melphalan supported by peripheral blood stem cells in previously untreated advanced ovarian cancer: A gynecologic oncology group study

Objectives. To evaluate the efficacy and safety of multiple cycles of high-dose carboplatin and paclitaxel and one consolidation cycle of high-dose melphalan with all cycles supported by hematopoietic stem cells and cytokine, in previously untreated patients with optimally debulked stage III epithelial ovarian cancer. Patients and Method. Patients had histologically, documented epithelial ovarian cancer and optimal initial cytoreductive surgery. No prior chemotherapy was permitted. Adequate performance status, bone marrow, hepatic, and renal function was required. After being mobilized with cyclophosphamide 3 g/m(2), paclitaxel 300 mg/m(2), and filgrastim 5 mug/kg/day, peripheral blood stem cells (PBSC) were collected by leukapheresis. Patients received three cycles of carboplatin AUC 15 mg (.) min/ml iv, paclitaxel 250 mg/m(2), and PBSC with filgrastim every 28 days, followed by one cycle of melphalan 140 mg/m(2) and hematopoietic support. Results. Nine patients entered the trial and received all planned cycles of chemotherapy. Of the eight patients who consented to surgical reassessment upon completing therapy, four had residual small-volume macroscopic disease, three had microscopic residual disease, and one had pathologic complete response. The estimated probability of a pathologic complete response was 12.5% (95% confidence interval: 0.3-52.7%). Hematologic toxicity was severe but manageable. Eleven of 45 cycles (24.4%) resulted in hospital admission for neutropenic fever, dehydration +/- diarrhea, syncope, or shortness of breath and pain secondary to tense ascites. Conclusions. The low pathological complete response rate did not justify toxicity; thus, the study was closed. High-dose chemotherapy as first-line treatment for epithelial ovarian cancer remains experimental and should be restricted to clinical trials. (C) 2002 Elsevier Science (USA).