Bortezomib for Patients with Advanced Stage Bronchioloalveolar Carcinoma (BAC): A California Cancer Consortium Phase II Study (NCI # 7003)

• Type of Material: Article
• Authors: Suresh S Ramalingam, Emory University; Angela M. Davies, University of California, Davis; Jeffrey Longmate, City of Hope Comprehensive Cancer Center; Martin J. Edelman, University of Maryland; Primo N. Lara, University of California, Davis; Everett E. Vokes, University of Chicago; Miguel Villalona-Calero, Ohio State University; Barbara Gitlitz, University of Southern California; Karen Reckamp, City of Hope Comprehensive Cancer Center; Ravi Salgia, University of Chicago; John J. Wright, National Cancer Institute; Chandra P. Belani, Pennsylvania State University; David R. Gandara, University of California, Davis
• Language: English
• Date: 2011-10
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 International Association for the Study of Lung Cancer
• Final Published Version (URL): http://dx.doi.org/10.1097%2FJTO.0b013e318225924c
• Title of Journal or Parent Work: Journal of Thoracic Oncology
• ISSN: 1556-0864
• Volume: 6
• Issue: 10
• Start Page: 1741
• End Page: 1745
• Grant/Funding Information: Supported by NCI NO1-CM-62209 (California Cancer Consortium), NO1-CM-62201 (University of Chicago Consortium), NO1-CM-62208 (Southeast Phase 2 Consortium)& NO1-CM-62207Ohio State University
• Keywords: proteasome inhibition; NSCLC; BAC; bortezomib; bronchioloalveolar carcinoma
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery

Abstract

Background Bronchioloalveolar carcinoma (BAC), a subtype of non-small cell lung cancer (NSCLC), is a difficult disease to treat with low response rates with cytotoxic chemotherapy. Bortezomib, a proteasome inhibitor, has demonstrated objective responses in BAC patients in early phase clinical trials. We conducted a phase II study of bortezomib inpatients with advanced stage BAC. Methods Patients with advanced BAC, adenocarcinoma with BAC features or BAC with adenocarcinoma features and less than two prior regimens were eligible. Prior epidermal growth factor receptor (EGFR) inhibitor therapy was allowed. Bortezomib was administered intravenously at 1.6 mg/m2 on days 1 and 8 of every 21 days cycle until disease progression or unacceptable toxicity. The primary endpoint was response rate. The Simon two-stage design was utilized. Results Forty-two patients were enrolled and the study was halted early for slow accrual. Patient characteristics were: female 55%, median age 68 years, and ECOG performance status of 0 and 1 in 31 and 11 patients respectively. Twenty-six(62%)patients had received prior therapy with an EGFR inhibitor. A median of 4 cycles of therapy were administered. Objective responses were noted in 5% while 57% had disease stabilization. The median progression-free survival and overall survival were 5.5 months and 13.6 months respectively. Grade 3 diarrhea and fatigue were noted in 3 and 5 patients respectively. Conclusions Bortezomib is tolerated well and is associated with modest anti-cancer activity in advanced BAC, including inpatients that progressed on EGFR inhibitor therapy.