Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer

Objective. The safety and efficacy of gemcitabine plus carboplatin (GC) or paclitaxel plus carboplatin (TC) induction regimens with or without paclitaxel consolidation therapy were assessed in ovarian cancer (OC). Methods. Patients with stage IC-IV OC were randomized to either GC (gemcitabine 1000 mg/m(2), days 1 and 8, plus carboplatin area under the curve [AUC] 5, day 1) or TC (paclitaxel 175 mg/m(2) plus carboplatin AUC 6, day 1) every 21 days for up to six cycles. Patients with complete response (CR) were allowed optional consolidation with paclitaxel 135 mg/m(2) every 28 days for <= 12 months. Patients without CR received single-agent crossover therapy at induction doses/schedules until CR, disease progression (PD), or unacceptable toxicity. PD or death in 636 patients was required to compare induction arms with 80% statistical power for progression-free survival (PFS), the primary endpoint. Results. Randomized induction therapy was received by 820 of 919 patients enrolled; 352 patients with CR received paclitaxel consolidation whereas 155 patients without CR received single-agent crossover therapy. PFS was similar for GC and TC (median, 20.0 and 22.2 months, respectively; P = .199). Despite high censoring rates (>52%), overall survival was longer for TC (median, 57.3 versus 43.8 months for GC; P = .013). Controlling for patient characteristics including performance status, residual tumor size, and tumor stage, there was no statistical difference in a multivariate analysis (HR = 1.22; 95% CI = 0.99-1.52; P = .067). Conclusions. GC does not improve PFS over TC as first-line induction chemotherapy in OC. Although favoring TC, overall survival analyses were limited by the study design and high censoring rates. (C) 2011 Elsevier Inc. All rights reserved.