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Multicenter Phase II Study of Oral Bexarotene for Patients With Metastatic Breast Cancer

Francisco J. Esteva, John Glaspy, Said Baidas, Leslie Laufman, Laura Hutchins, Maura Dickler, Debu Tripathy, Roger Cohen, Angela DeMichele, Richard C. Yocum, C. Kent Osborne, Daniel F. Hayes, Gabriel N. Hortobagyi, Eric Winer, George D. Demetri

From the University of Texas M.D. Anderson Cancer Center, and Baylor College of Medicine; Houston, TX; Dana-Farber Cancer Institute, Boston, MA; Georgetown University, Washington, DC; Hematology/Oncology Consultants, Columbus, OH; Ligand Pharmaceuticals Inc, San Diego; University of California Los Angeles, Los Angeles; University of California San Francisco, San Francisco, CA; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Arkansas for Medical Sciences, Little Rock, AR; University of Michigan, Ann Arbor, MI; University of Pennsylvania Cancer Center, Philadelphia, PA; and University of Virginia, Charlottesville, VA.

Address reprint requests to Francisco J. Esteva, MD, PhD, Departments of Breast Medical Oncology, and Molecular and Cellular Oncology The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 424, Houston, TX 77030; email: festeva{at}mdanderson.org.

Purpose: Bexarotene is a retinoid X receptor–selective retinoid that has preclinical antitumor activity in breast cancer. We evaluated the efficacy and safety of oral bexarotene in the treatment of patients with metastatic breast cancer.

Patients and Methods: The following three groups of patients were treated: hormone-refractory, chemotherapy-refractory, and tamoxifen-resistant patients. Patients in the first two groups were treated with bexarotene alone, whereas the tamoxifen-resistant patients received both tamoxifen and bexarotene. Patients in all groups were randomly assigned to receive bexarotene at either 200 or 500 mg/m²/d.

Results: One hundred forty-eight patients were randomized; 145 patients were treated. Of 48 hormone-refractory patients, there were two partial responses (6%) and 10 patients with stable disease lasting more than 6 months; of 47 chemotherapy-refractory patients, there were two partial responses (6%) and five patients with stable disease; and of 51 tamoxifen-resistant patients, there was one partial response (3%) and 11 patients with stable disease. All partial responses occurred at the 200-mg/m²/d dose. The projected median time to progression across all of the arms was 8 to 10 weeks. There were no drug-related deaths, and only two patients had drug-related serious adverse events. The most common drug-related adverse events were hypertriglyceridemia (84%), dry skin (34%), asthenia (30%), and headache (27%). There were no cases of pancreatitis.

Conclusion: The efficacy of bexarotene in patients with refractory metastatic breast cancer is limited. However, it is an oral agent with minimal toxicity and a unique mechanism of action, which produced clinical benefit in approximately 20% of patients. Future efforts should define populations likely to benefit from this agent.

This study was supported in part by Ligand Pharmaceuticals Inc, San Diego, CA. F.J.E. is a recipient of Career Development Award no. K23-CA82119 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.

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