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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.

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