Bexarotene

Bexarotene (Targretin) is an oral antineoplastic agent indicated by the FDA for Cutaneous T cell lymphoma. It has been used off-label for lung cancer, breast cancer, and Kaposi's sarcoma.

Administration
In Europe oral bexarotene is licensed for use in patients with skin manifestations of cutaneous T cell lymphoma who have had at least one systemic therapy. It is effective in reducing the patches plaques and tumours caused by the disease in half of the patients treated, and three quarters of patients report feeling better while on therapy (Duvic et al). The usual dose taken is 300mg/m2 a day.

Side effects
Side effects of therapy include hypothyroidism and raised triglycerides which occur in nearly all patients. The response is seen in about 3 months and will last for about a year.

Mechanism
Bexarotene is a rexinoid specifically selective for retinoid X receptors, as opposed to the retinoic acid receptors.

RXRs are located primarily in visceral organs such as the liver and kidney. Activated RXRs form homodimers or heterodimers with RAR (retinoic acid receptors), vitamin D receptors, thyroid receptors or peroxisome proliferator activator receptors. Once activated, these retinoid receptor dimers bind to DNA at retinoic acid response elements and act as transcription factors that regulate the expression of genes which control cellular differentiation and proliferation. Retinoid agonists can activate the expression of retinoid regulated genes by removing negative transcription control or by facilitating positive transcriptional activity. They exert anticancer action by interfering with the growth of cells of the tumor.