Phase III study of valspodar (PSC 833) combined with paclitaxel and carboplatin compared with paclitaxel and carboplatin alone in patients with stage IV or suboptimally debulked stage III epithelial ovarian cancer or primary peritoneal cancer

PURPOSE: To compare the safety and efficacy of carboplatin and paclitaxel administered with or without the multidrug resistance modulator valspodar (PSC 833) in untreated patients with advanced ovarian or primary peritoneal cancer. PATIENTS AND METHODS: Seven hundred sixty-two patients with stage IV or suboptimally debulked stage III ovarian or primary peritoneal cancer were randomly assigned to receive either valspodar 5 mg/kg every 6 hours for 12 doses, paclitaxel 80 mg/m(2), and carboplatin area under the curve (AUC) 6 (PC-PSC; n = 381) or paclitaxel 175 mg/m(2) and carboplatin AUC 6 (PC; n = 381). Time to disease progression (TTP) was the primary end point. Secondary end points were overall survival time (OS), response rate (RR), safety, and tolerability. RESULTS: With a median follow-up of 736 days (range, 1 to 2,280 days), the median TTP was 13.2 and 13.5 months in the PC-PSC and PC groups, respectively (P = .67); the median OS was 32 and 28.9 months, respectively (P = .94). The overall RR was higher in the PC group (41.5% v 33.6%; P = .02). Central and peripheral nervous system and GI toxicities were more common in the PC-PSC group. Ataxia occurred in 53.5% and 3.2% of PC-PSC-and PC-treated patients, respectively. Febrile neutropenia occurred more frequently in the PC-PSC group. More PC-PSC-treated patients discontinued therapy because of adverse events (AEs), experienced serious AEs, and required paclitaxel dose reductions. CONCLUSION: The addition of valspodar to PC did not improve TTP or OS and was more toxic compared with PC in untreated patients with advanced ovarian or primary peritoneal cancer.