New Drug for Refractory Cutaneous T-Cell Lymphoma

The US Food and Drug Administration (FDA) has approved bexarotene (Targretin) for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have not responded to at least one prior systemic therapy. Bexarotene is a member of a subclass of retinoids that selectively activate retinoid X receptors. When activated, these receptors function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation. However, bexarotene is associated with birth defects in humans, and must not be administered to a woman who is or intends to become pregnant.

Evaluated in Two Studies

Bexarotene was evaluated in 152 patients with advanced and early-stage CTCL in two studies. Of the 102 patients with disease refractory to at least one prior systemic therapy, 90 had advanced disease and had received a median of five prior systemic, radiation, and/or topical therapies. Twelve patients with early disease had received a median of 3.5 therapies, and were intolerant to, did not respond to, or had reached a response plateau of 6 months while receiving at least two therapies.

Tumor response was assessed in both studies by observation of as many as five baseline-defined index lesions using a composite assessment of index lesion disease severity. All tumor responses required confirmation by at least two assessments that were performed at least 4 weeks apart.

Initial daily doses of bexarotene of 650 or 500 mg/m², administered to 40 people, were not tolerated. Of the 62 patients who received an initial daily dose of 300 mg/m², 1 (1.6%) achieved a complete clinical tumor response and 19 (30.6%) achieved partial responses. Of these 20 responding patients, 6 (31.5%) experienced a relapse during a median period of 21 weeks.

Lipid Abnormalities Common

Bexarotene induced major lipid abnormalities in most patients. About 70% of patients with CTCL who received an initial daily dose of at least 300 mg/m² had fasting triglyceride levels greater than 2.5 times the upper limit of the normal range, and approximately 60% of patients with CTCL on the same regimen had cholesterol levels of more than 300 mg/dL (7.76 mmol/L). Levels of high-density lipoprotein (HDL) cholesterol were reduced, but about 30% of patients developed hypothyroidism and needed replacement therapy.