Methods and Findings in Experimental and Clinical Pharmacology
Vol. 25, Suppl. A, 2003
ISSN 0379-0355
Copyright 2003 Prous Science, S.A.
CCC: 0379-0355/2003
http://www.prous.com

Bexarotene, a New Option for the Treatment of CTCL, Approved by the FDA and the EMEA

I. Zsolt

Laboratorios Ferrer Internacional, S.A.

Bexarotene is a synthetic retinoid compound that exerts its biological action through selective binding and activation of the three RXRs: a, b and g. Once activated, these receptors function as transcription factors that regulate processes such as cellular differentiation and proliferation, apoptosis and insulin sensitization. The ability of RXRs to form heterodimers with various receptor partners important in cellular function and physiology indicates that the biological activities of bexarotene are more diverse than those of compounds that activate the RARs. Bexarotene inhibits the growth of tumor cell lines of hematopoietic and squamous cell origin in vitro. In vivo, bexarotene causes tumor regression in some animal models and prevents tumor induction in others.

Bexarotene capsules were evaluated in a clinical trial of 193 patients with CTCL of whom 93 had advanced stage disease refractory to prior systemic therapy. Among 61 patients treated at an initial dose of 300 mg/m²/day, the overall response rate, according to a global assessment by the physician, was 51% (31/61). Responses were also determined by a composite score of five clinical signs (surface area, erythema, plaque elevation, scaling and hypo/hyperpigmentation) which also considered all extracutaneous CTCL manifestations. The overall response rate according to this composite assessment was 31% (19/61), with a clinical complete response rate of 7% (4/61). Recent data show that patients taking 2 lipid lowering agents (LLA), had a significantly higher response rate of 90% than those taking one or no LLA (p < 0.0001). Enhanced efficacy when combined with IFNa and/or PUVA has been reported.

The pharmaceutical form of bexarotene are capsules of 75 mg of active product. The efficacy of the treatment is dose-dependent. The recommended initial dose is 300 mg/m²/day. Treatment should be continued as long as the patient is deriving benefit.

During clinical trials, the most common adverse reactions reported were leukopenia, hypothyroidism, hyperlipemia, hypercholesterolemia, skin alterations such as pruritus, rash, exfoliative dermatitis, liver function tests abnormalities, headache, asthenia and pain. Patients therefore have to be maintained by physicians experienced in the treatment of patients with CTCL. Patients should be monitored to detect possible initial thyroid test alterations, increases in lipid levels, liver function test alterations, anemia or leukopenia. If initially detected, these problems can be easily solved with an appropriate treatment. As with other retinoids, administration during pregnancy is not recommended, and women with childbearing potential should use adequate birth-control measures if administered.

Methods and Findings in Experimental and Clinical Pharmacology Vol. 25, Suppl. A, 2003
ISSN 0379-0355 Copyright 2003 Prous Science, S.A. CCC: 0379-0355/2003 http://www.prous.com