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Journal of Clinical Oncology, Vol 19, Issue 9 (May), 2001: 2456-2471
© 2001 American Society for Clinical Oncology

Bexarotene Is Effective and Safe for Treatment of Refractory Advanced-Stage Cutaneous T-Cell Lymphoma: Multinational Phase II-III Trial Results

By Madeleine Duvic, Kenneth Hymes, Peter Heald, Debra Breneman, Ann G. Martin, Patricia Myskowski, Connie Crowley, Richard C. Yocum, for Members of the Bexarotene Worldwide Study Group

From the M.D. Anderson Cancer Center, Houston, TX; New York University and Memorial Sloan-Kettering Cancer Center, New York, NY; Yale University, New Haven, CT; University of Cincinnati, Cincinnati, OH; Washington University, St. Louis, MO; and Ligand Pharmaceuticals Inc., San Diego, CA.

Address reprint requests to Madeleine Duvic, MD, Chairman ad interim, Department of Dermatology, M.D. Anderson Cancer Center, Box 434, 1515 Holcombe Blvd, Houston, TX 77030; email: mduvic@ mdanderson.org.

PURPOSE: Cutaneous T-cell lymphomas (CTCL) are malignancies of T cells appearing as skin lesions and are responsive to retinoid therapy. Safety and efficacy of a novel RXR-selective retinoid (rexinoid) bexarotene (Targretin, LGD1069; Ligand Pharmaceuticals Inc, San Diego, CA) was evaluated as a single-agent oral therapy administered once daily in an open-label study in patients with refractory advanced-stage CTCL.

PATIENTS AND METHODS: Ninety-four patients with biopsy-confirmed CTCL in advanced stages (IIB-IVB) were enrolled at 26 centers. Fifty-six patients received an initial dose of 300 mg/m2/d oral bexarotene and 38 started at more than 300 mg/m2/d.

RESULTS: Clinical complete and partial responses were reported by Primary End point Classification for the study in 45% (25 of 56) of patients enrolled at 300 mg/m2/d dosing. At more than 300 mg/m2/d, 55% (21 of 38) of patients responded, including 13% (five of 38) clinical complete. For the 300 mg/m2/d initial dose group, the rate of relapse after response was 36% and the projected median duration of response was 299 days. Improvements were also seen in overall body-surface area involvement, median index lesion surface area, adenopathy, cutaneous tumors, pruritus, and CTCL-specific quality of life. The most frequent drug-related adverse events included hypertriglyceridemia (associated rarely with pancreatitis), hypercholesterolemia, hypothyroidism, and headache.

CONCLUSION: Bexarotene is the first in a novel class of pharmacologic agents, the RXR-selective retinoids, or rexinoids. Bexarotene is orally administered, safe, and generally well tolerated with reversible side effects, and is effective for the treatment of advanced, refractory CTCL.

Presented in part at the American Society of Hematology meeting in New Orleans, LA, December 5-9, 1999.

C.C. and R.Y. are employees of Ligand Pharmaceuticals Inc.




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