Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: Multinational phase II-III trial results

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/m(2)/d oral bexarotene and 38 started at more than 300 mg/m(2)/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/m(2)/d dosing. At more than 300 mg/m(2)/d, 55% (21 of 38) of patients responded, including 13% (five of 38) clinical complete. For the 300 mg/m(2)/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. J Clin Oncol 19:2456-2471. (C) 2001 by American Society of Clinical Oncology.