A Phase 2 Trial of Flavopiridol (Alvocidib) and Cisplatin in Platin-Resistant Ovarian and Primary Peritoneal Carcinoma: MC0261

Purpose. Based upon promising preclinical and phase 1 trial results, combined flavopiridol and cisplatin therapy was evaluated in patients with ovarian and primary peritoneal cancers. Methods. A two cohort phase 2 trial of cisplatin (60 mg/m(2) IV) immediately followed by flavopiridol (100 mg/m(2) IV, 24 h infusion; 21 day cycles) was undertaken in patients with recurrent platin-sensitive or platin-resistant disease (progression > vs. <= 6 months following prior platin-based therapy). Measurable disease (RECIST) - or evaluable disease plus CA125 > 2X post-treatment nadir - and ECOG performance <= 2 were required. Results. Forty-five patients were enrolled between December 23, 2004 and February 25, 2010: 40 platin-resistant (Group 1), and 5 platin-sensitive (Group 2). ill Group 1, the median number of treatment cycles was 3 (range 2-12). Only 10% of patients incurred grade 4 toxicities, but grade 3 toxicities were common (65%): neutropenia (17.5%); nausea (12.5%); vomiting, fatigue, thrombosis, anemia (10% each). Seven patients (17.5%) achieved a confirmed response (1 CR, 6 PR; median duration 118 days); ten additional patients (25%) attained maintained stable disease. Median time to progression was 4.3 months; overall survival was 16.1 months. Pilot translational studies assessed ascites flavopiridol level: surrogate marker studies were uninformative. In Group 2, although 4 of 5 patients responded (2 confirmed PRs with median time to progression, 10.8 months and median overall survival 20.6 months) the cohort was closed due to poor accrual. Conclusions. The assessed flavopiridol and cisplatin regimen displayed clinical activity in platin resistant and sensitive ovarian/primary peritoneal cancers, meriting further study. (C) 2012 Elsevier Inc. All rights reserved.