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

Abstract

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.

Figure 1

Dose-escalation flow chart. Abbreviations: DTL, dose-limiting toxicity; MTD, maximum tolerated dose. ^aPatients were allowed to receive additional courses at the dose level at which they began treatment.

Figure 2

Maximum tumour reduction in target lesions within six cycles of treatment in patients with measurable disease (full analysis set). ^aResponders were determined by a tumour response rate (or reduction in the size of target lesions) of −30%.

Figure 3

Maximum reduction in CA125 levels within six cycles of treatment (full analysis set). ^aOne patient in the 12mg m⁻² treatment group was excluded due to unavailable baseline CA125 measurement.^b Response was defined as a −50% reduction in CA125 levels compared with the pretreatment sample.