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

Abstract

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.

• Authors: M Duvic, K Hymes, P Heald, D Breneman, A G Martin, P Myskowski, C Crowley, R C Yocum, Bexarotene Worldwide Study Group
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 19 Issue 9 Pg. 2456-71 (May 01 2001) ISSN: 0732-183X [Print] United States
• PMID: 11331325 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anticarcinogenic Agents
• Tetrahydronaphthalenes
• Bexarotene

Topics

• Adult
• Aged
• Aged, 80 and over
• Anticarcinogenic Agents (therapeutic use)
• Bexarotene
• Female
• Humans
• Lymphoma, T-Cell, Cutaneous (drug therapy, mortality)
• Male
• Middle Aged
• Quality of Life
• Tetrahydronaphthalenes (adverse effects, pharmacokinetics, therapeutic use)