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Phase II Trial of Bexarotene Capsules in Patients With Advanced Non–Small-Cell Lung Cancer After Failure of Two or More Previous Therapies

Ramaswamy Govindan, John Crowley, Lee Schwartzberg, Peter Kennedy, Charles Williams, Bradley Ekstrand, Alan Sandler, Dinah Jaunakais, Vanessa Bolejack, Richard Ghalie

From the Washington University School of Medicine, St Louis, MO; Cancer Research and Biostatistics, Seattle, WA; The West Clinic, Memphis, TN; Kenmar Research Institute, Los Angeles; California Cancer Care, San Mateo; Ligand Pharmaceuticals Inc, San Diego, CA; Moffitt Cancer Center, Tampa, FL; and the Vanderbilt Ingram Cancer Center, Nashville, TN

Address reprint requests to Ramaswamy Govindan, MD, Associate Professor of Medicine, Washington University School of Medicine, 4960 Children's Place, Suite 108, St Louis, MO 63110; e-mail: rgovinda{at}im.wustl.edu

PURPOSE: To evaluate the effect of bexarotene on survival in patients with relapsed non–small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: Patients with stage IIIB NSCLC with pleural effusion or stage IV NSCLC, who had Eastern Cooperative Oncology Group performance status 0 to 2, and were previously treated with two different regimens that must have included a platinum and a taxane, received oral bexarotene 400 mg/m²/d plus concomitant levothyroxine and a lipid-lowering agent. Primary efficacy end point was survival.

RESULTS: For the 146 assessable patients treated with bexarotene, median age was 66 years (range, 34 to 87 years), 51% were men, and the median number of prior regimens was three (range, one to seven). The overall median survival was 5 months (95% CI, 4 to 7 months) and the 1-year survival was 23% (95% CI, 16% to 31%). Survival was significantly longer in patients with bexarotene-induced hypertriglyceridemia and/or skin rash. In 26 patients who had both adverse effects, the median and 1-year survival rates were 12 months (95% CI, 8 to 15 months) and 48%, respectively. In 40 patients who had neither adverse effect, median and 1-year survival rates were 2 months (95% CI, 2 to 5 months) and 15%, respectively (P = .0002). Twenty patients (14%) discontinued therapy because of bexarotene-related toxicity. For the remaining patients, adverse reactions to bexarotene were generally mild to moderate.

CONCLUSION: In the intent-to-treat population, bexarotene given as third or subsequent line of therapy for relapsed NSCLC did not achieve the intended median survival of 6 months. Survival may have been extended in patients who developed bexarotene-induced hypertriglyceremia and/or skin rash. It is important to confirm these observations in a randomized controlled trial.

Supported by Ligand Pharmaceuticals Inc, San Diego, CA.

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005, and in poster format at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006.

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

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