Phase I/II study of sagopilone (ZK-EPO) plus carboplatin in women with recurrent platinum-sensitive ovarian cancer

BACKGROUND: Sagopilone is the first fully synthetic epothilone in clinical development and has demonstrated promising preclinical activity. This phase I/II, prospective, open-label trial investigated the efficacy and safety of sagopilone plus carboplatin in patients with recurrent platinum-sensitive ovarian cancer (OC). METHODS: In phase I (dose-escalation stage), patients with OC recurring at least 6 months after platinum-containing chemotherapy received 3-h infusions of sagopilone (initial dose of 12 mg m(−2)) followed by carboplatin every 3 weeks, for 2–6 treatment courses. Patients enrolled in phase II received 3-h infusions of 16 mg m(−2) sagopilone. Efficacy was assessed using modified Response Evaluation Criteria in Solid Tumors (modRECIST) and Gynecologic Cancer InterGroup CA125 criteria. The safety and tolerability of sagopilone were also evaluated. RESULTS: In all, 45 patients received sagopilone at 12 mg m(−2) or 16 mg m(−2). There were 29 confirmed tumour responses (21 modRECIST and 8 CA125) across both treatment groups, indicating that the primary objective of the study was reached. The main adverse events (AEs) reported were peripheral neuropathy (75.6%), fatigue (71.1%) and nausea (64.4%). Grade ⩾3 AEs occurred in 35 patients (77.8%). No deaths related to the study drug were reported. CONCLUSION: Sagopilone in combination with carboplatin was effective and toxicities were manageable in patients with recurrent platinum-sensitive OC.