Bortezomib with or without irinotecan in relapsed or refractory colorectal cancer: Results from a randomized phase II study

Abstract

Purpose: To evaluate the efficacy and toxicity of bortezomib with or without irinotecan, in patients with relapsed or refractory colorectal cancer (CRC). Patients and Methods: Patients were randomly assigned in a 3:4 ratio to bortezomib 1.5 mg/m2 (arm A) or bortezomib 1.3 mg/m2 plus irinotecan 125 mg/m2 (arm B). A treatment cycle of 21 days consisted of four bortezomib doses on days 1, 4, 8, and 11, plus, in arm B, irinotecan on days 1 and 8. The primary objective of this randomized, multicenter, open-label, phase II study was to determine tumor response to treatment. Secondary objectives were safety and tolerability. Results: A preplanned interim analysis to assess efficacy revealed inadequate activity, resulting in early termination of this study. A total of 102 patients were treated, 45 in arm A and 57 in arm B. Baseline characteristics were comparable. The investigator-assessed response rate was 0 in arm A and 3.5% in arm B (all partial responses). Adverse events in both treatment arms were as expected, with no significant additive toxicity. The most common grade ≥ 3 adverse events reported, per patient, during the study were fatigue (27%), vomiting (13%), nausea (11%), and peripheral sensory neuropathy (11%) in arm A, and diarrhea (33%), fatigue (25%), neutropenia (23%), thrombocytopenia (18%), dyspnea (12%), abdominal pain (12%), dehydration (12%), and anemia (11%) in arm B. Conclusion: Bortezomib alone or in combination with irinotecan was not effective in patients with relapsed or refractory CRC. © 2008 by American Society of Clinical Oncology.