Clinical activity of patupilone in patients with pretreated advanced/metastatic colon cancer: Results of a phase i dose escalation trial

Background: New agents that are active in patients with metastatic colorectal cancer are needed. Patupilone (EPO906; epothilone B) is a novel microtubule-stabilising agent.Methods: Patients with advanced colon cancer who progressed after prior treatment regimens received intravenous patupilone (6.5-10.0 mg m-2) once every 3 weeks by a 20-min infusion (20MI), 24-h continuous infusion (CI-1D) or 5-day intermittent 16-h infusion (16HI-5D). Adverse events (AEs), dose-limiting toxicities (DLTs), pharmacokinetics and anti-tumour activity were assessed. Results: Sixty patients were enrolled. The maximum tolerated dose (MTD) was not reached in the 20MI arm (n31), as no DLTs were observed. Three patients in the CI-1D arm (n26) experienced 1 DLT each at 7.5, 8.0 and 9.0 mg m-2, but MTD was not reached. However, the prolonged 16HI-5D arm was terminated at 6.5 mg m-2 after two of the three patients developed a DLT. Diarrhoea was the most common AE and DLT, with increased severity at the higher doses (9.0 and 10.0 mg m-2). Grade 3 or 4 diarrhoea was observed in 11 (35%) of the patients in the 20MI arm, 4 (15%) of the patients in the CI-1D arm and 2 (67%) of the patients in the 16HI-5D arm. Patupilone activity was observed in the 20MI arm with a disease control rate of 58%, including four confirmed partial responses. The disease control rate in CI-1D arm was 39%.Conclusion:Patupilone given once every 3 weeks as a 20-min infusion had promising anti-tumour activity and manageable safety profile at doses that demonstrated therapeutic efficacy. © 2011 Cancer Research UK All rights reserved.