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 po or response to therapy and limited survival. We investigated the addit ion of dose-intense paclitaxel to cisplatin and cyclo-phosphamide for patients with FIGO III/IV epithelial ovarian cancer. Paclitaxel dose w as 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 cyclophosph amide 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 p aclitaxel at 250 mg/m(2), cisplatin at 75 mg/m(2), and cyclophosphamid e at 750 mg/m(2) on a 21-day cycle with G-CSF, 10 mu g/kg/day. Adminis tered dose intensity at the MTD was greater than or equal to 86%. Reve rsible grade 3 peripheral neuropathy occurred in 28% of patients and f ever during neutropenia in 2/352 cycles (0.5%). The pathologic respons e rate is 36% with an additional 25% having minimal microscopic diseas e, Median progression-free and overall survivals for patients receivin g paclitaxel at 250 mg/m(2) at a median potential follow-up of 22 mont hs have not been reached for the cohort nor for the greater than or eq ual to 3-cm subgroup. This regimen should he evaluated in a prospectiv e, randomized clinical trial. (C) 1996 Academic Press, Inc.