Weekly paclitaxel (wP) as single agent or in combination with weekly topotecan (wT) or carboplatin (C) in patients with resistant ovarian cancer (ROC): The phase II CARTAXHY randomized trial from GINECO

Abstract

5557 Background: For ROC patients (pts) with early progression during or after (< 6 months) platinum and 3 weekly P, use of single non-platinum agent including wP is standard (Kristensen G, et al. J Clin Oncol 26: 2008 abstr 5508). Few randomized trials have explored combination therapy in this setting. Methods: Pts with ROC after a first or second line including a platinum and a taxane were randomized to receive wP (80 mg/m2/week) alone or in combination with wT (3mg/m2/week) or C (AUC 5 every 4 weeks). The primary end-point was the comparison of progression-free survival (PFS) between single non-platinum agent and combination therapy (wP+wT or wP+C). Secondary objectives included safety, QoL, response rate (RR) and overall survival. Results: From April 2004 to August 2008, 165 pts were accrued (wP 57, wP+wT 57, wP+C 51). Median number of cycles and P dose-intensity (mg/m2/week) was 4.6 and 70, 4.2 and 63 in monotherapy and combination therapy arms respectively. Non-hematological toxicity was not different between the arms, except an excess of hypersensitivity reactions in the wP+C arm. Grade 3–4 neutropenia (48 vs 13% of pts), and anemia (24 vs 6%) were more frequent in combination therapy than in single agent arm and similar with wT or C combination. Febrile neutropenia was experienced by 5 pts treated with combination therapy. Discontinuation from drug treatment was more frequent with combination therapy (24% of pts) than with monotherapy (4%), mainly due to hematotoxicity. RR was 34, 38 and 39% for wP, wP+wT and wP+C respectively. Median PFS of pts treated with single agent (112 days) was not significantly different from those treated with combination therapy (149 days) (p = 0,62) and was similar in wP+wT (152 days) or wP+C (146 days) arms. Treatment with single non-platinum agent or combination therapy was not found an independent parameter when added to a Cox model including prognostic variables. Conclusions: Combination therapy (CT) in platinum resistant ovarian cancer was found more toxic than weekly paclitaxel and the PFS advantage from CT was not statistically significant. No significant financial relationships to disclose.