A phase I/II study of dose-intense paclitaxel with cisplatin and cyclophosphamide as initial therapy of poor-prognosis advanced-stage epithelial ovarian cancer

Epithelial ovarian cancer patients with bulky residual tumor have a poor response to therapy and limited survival. We investigated the addition of dose-intense paclitaxel to cisplatin and cyclo-phosphamide for patients with FIGO III/IV epithelial ovarian cancer. Paclitaxel dose was intensified from 135 to 250 mg/m(2) and administered in combination with cisplatin at greater than or equal to 75 mg/m(2) and cyclophosphamide at 750 mg/m(2). Thirty-one of 36 patients (86%) and 25 (70%) had greater than or equal to 2 and greater than or equal to 3 cm residual disease after surgery, respectively, One-third had stage IV disease, and 80% had grade 3 tumors, The maximally tolerated doses (MTD) were paclitaxel at 250 mg/m(2), cisplatin at 75 mg/m(2), and cyclophosphamide at 750 mg/m(2) on a 21-day cycle with G-CSF, 10 mu g/kg/day. Administered dose intensity at the MTD was greater than or equal to 86%. Reversible grade 3 peripheral neuropathy occurred in 28% of patients and fever during neutropenia in 2/352 cycles (0.5%). The pathologic response rate is 36% with an additional 25% having minimal microscopic disease, Median progression-free and overall survivals for patients receiving paclitaxel at 250 mg/m(2) at a median potential follow-up of 22 months have not been reached for the cohort nor for the greater than or equal to 3-cm subgroup. This regimen should he evaluated in a prospective, randomized clinical trial. (C) 1996 Academic Press, Inc.