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Bortezomib With or Without Irinotecan in Relapsed or Refractory Colorectal Cancer: Results From a Randomized Phase II Study

Peter S. Kozuch, Caio Max Rocha-Lima, Tomislav Dragovich, Howard Hochster, Bert H. O'Neil, Omar T. Atiq, J. Marc Pipas, David P. Ryan, Heinz-Josef Lenz

From the Continuum Cancer Centers of New York, St Luke's-Roosevelt Hospital; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL; Arizona Cancer Center, Tucson, AZ; New York University School of Medicine, New York, NY; University of North Carolina School of Medicine, Chapel Hill, NC; Arkansas Cancer Institute, Pine Bluff, AK; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, NH; Massachusetts General Hospital, Harvard Medical School, Boston, MA; and the University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA

Corresponding author: Heinz-Josef Lenz, MD, University of Southern California Norris Comprehensive Cancer Center, 1441 Eastlake Ave, NOR 3456, Los Angeles, CA 90033; e-mail: lenz{at}usc.edu

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.

Supported by Millennium Pharmaceuticals Inc, and Johnson & Johnson Pharmaceutical Research and Development.

Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.