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Randomized Phase II Study of Bortezomib Alone and Bortezomib in Combination With Docetaxel in Previously Treated Advanced Non–Small-Cell Lung Cancer

Michael P. Fanucchi, Frank V. Fossella, Robert Belt, Ronald Natale, Panos Fidias, David P. Carbone, Ramaswamy Govindan, Luis E. Raez, Francisco Robert, Maria Ribeiro, Wallace Akerley, Karen Kelly, Steven A. Limentani, Jeffrey Crawford, Hans-Joachim Reimers, Rita Axelrod, Oscar Kashala, Shihong Sheng, Joan H. Schiller

From the Winship Cancer Institute, Emory University School of Medicine, Atlanta; Atlanta Veterans Affairs Medical Center, Decatur, GA; University of Texas M.D. Anderson Cancer Center, Department of Thoracic/Head and Neck Medical Oncology, Houston; University of Texas Southwestern, Dallas, TX; Kansas City Oncology Hematology Group, DBA Kansas City Cancer Centers, Kansas City; Washington University, Medical Oncology, Barnard Cancer Center; St Louis University Health Sciences Center, St Louis, MO; Cedars-Sinai Comprehensive Cancer Center, Los Angeles, CA; Massachusetts General Hospital, Boston; Millennium Pharmaceuticals Inc, Cambridge, MA; Vanderbilt University-Clinical Trials Center, Nashville, TN; Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; University of Colorado Health Sciences Center, Aurora, CO; Carolinas Hematology-Oncology Associates, Blumenthal Cancer Center, Charlotte; Duke University Medical Center, Durham, NC; and Kimmel Cancer Center at Jefferson, Philadelphia, PA

Address reprint requests to Joan H. Schiller, MD, University of Texas Southwestern, Division of Hematology/Oncology, 5323 Harry Hines Blvd, Dallas, TX 75390-8852; e-mail: joan.schiller{at}utsouthwestern.edu

Purpose To evaluate the efficacy and toxicity of bortezomib ± docetaxel as second-line therapy in patients with relapsed or refractory advanced non–small-cell lung cancer (NSCLC).

Patients and Methods Patients were randomly assigned to bortezomib 1.5 mg/m² (arm A) or bortezomib 1.3 mg/m² plus docetaxel 75 mg/m² (arm B). A treatment cycle of 21 days comprised four bortezomib doses on days 1, 4, 8, and 11, plus, in arm B, docetaxel on day 1. Patients could receive unlimited cycles. The primary end point was response rate.

Results A total of 155 patients were treated, 75 in arm A and 80 in arm B. Baseline characteristics were comparable. Investigator-assessed response rates were 8% in arm A and 9% in arm B. Disease control rates were 29% in arm A and 54% in arm B. Median time to progression was 1.5 months in arm A and 4.0 months in arm B. One-year survival was 39% and 33%, and median survival was 7.4 and 7.8 months in arms A and B, respectively. Adverse effect profiles were as expected in both arms, with no significant additivity. The most common grade 3 adverse events were neutropenia, fatigue, and dyspnea (4% and 53%, 19% and 26%, and 17% and 14% of patients in arms A and B, respectively).

Conclusion Bortezomib has modest single-agent activity in patients with relapsed or refractory advanced NSCLC using this schedule, with minor enhancement in combination with docetaxel. Additional investigation of bortezomib in NSCLC is warranted in combination with other drugs known to be active, or using different schedules.

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

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL, and the 11th World Conference on Lung Cancer (IASLC), July 3-7, 2005, Barcelona, Spain.

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

Published by the American Society of Clinical Oncology

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