Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in people who are refractory to at least one prior systemic therapy and for the topical treatment of cutaneous lesions in patients with CTCL who have refractory or persistent disease after other therapies or who have not tolerated other therapies. It has been used off-label for non-small cell lung cancer and breast cancer.
Contraindications
Known contraindications include:
Hypersensitivity to the active substance or to any of the excipients in the preparation.
Pregnancy and lactation
Women of child-bearing potential without effective birth-control measures
Overall the most common adverse effects are skin reactions, leucopenia, headache, weakness, thyroid anomalies and blood lipid anomalies such as hypercholesterolaemia and hyperlipidaemia, hypothyroidism.
Interactions
Its plasma concentration may be increased by concomitant treatment with CYP3A4 inhibitors such as ketoconazole. It may also induce CYP3A4, and hence CYP3A4 substrates like cyclophosphamide may have their plasma concentrations reduced. Likewise consumption of grapefruit juice might increase bexarotene's plasma concentrations, hence potentially altering its therapeutic effects.
Mechanism
Bexarotene is a retinoid that selectively activates retinoid X receptors, as opposed to the retinoic acid receptors, the other major target of retinoic acid. By so doing it induces cell differentiation and apoptosis and prevents the development of drug resistance. It also has anti-angiogenic effects and inhibits cancer metastasis. The retinoic acid receptors regulate cell differentiation and proliferation whereas RXRs regulate apoptosis.
Physical properties
Bexarotene is a solid, white powder. It is poorly soluble in water; the solubility is estimated to be about 10-50 μM. It is soluble in DMSO at 65 mg/mL and in ethanol at 10 mg/mL with warming.
History
and the La Jolla Cancer Research Foundation collaborated on work that resulted in patent filings for the drug. The developer of bexarotene was Ligand Pharmaceuticals, a San Diegobiotech company which received FDA approval for the drug in 1999. The FDA approved bexarotene on 29 December 1999. Japanese pharmaceutical Eisai bought the rights to Targretin and three other anti-cancer products from Ligand in 2006. In the United States, patents on the drug expired in 2016. It received EMA approval on 29 March 2001. Early-stage preclinical studies suggested that bexarotene reduced amyloid plaques and improved mental functioning in a small sample of mice engineered to exhibit Alzheimer's-like symptoms although subsequent studies have yielded mixed results.
