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.

• Authors: S McMeekin, R Patel, C Verschraegen, P Celano, J Burke 2nd, S Plaxe, P Ghatage, M Giurescu, C Stredder, Y Wang, T Schmelter
• Journal: British journal of cancer (Br J Cancer) Vol. 106 Issue 1 Pg. 70-6 (Jan 03 2012) ISSN: 1532-1827 [Electronic] England
• PMID: 22108514 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Benzothiazoles
• Epothilones
• Carboplatin
• sagopilone

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Benzothiazoles (administration & dosage)
• Carboplatin (administration & dosage)
• Epothilones (administration & dosage)
• Female
• Humans
• Middle Aged
• Ovarian Neoplasms (drug therapy, pathology)
• Recurrence