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 (oral) 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 (topical).[3]
Overall the most common adverse effects are skin reactions (mostly itchiness and rashes), leucopenia, headache, weakness, thyroid anomalies (which seem to be mediated by RXR-mediated downregulation of thyroid stimulating hormone) and blood lipid anomalies such as hypercholesterolaemia (high blood cholesterol) and hyperlipidaemia, hypothyroidism.[3][10][11][12]
Interactions
Its plasma concentration may be increased by concomitant treatment with CYP3A4 inhibitors such as ketoconazole.[10] It may also induce CYP3A4, and hence CYP3A4 substrates like cyclophosphamide may have their plasma concentrations reduced.[10] Likewise consumption of grapefruit juice might increase bexarotene's plasma concentrations, hence potentially altering its therapeutic effects.[10]
Mechanism
Bexarotene is a retinoid that selectively activates retinoid X receptors (RXRs), as opposed to the retinoic acid receptors, the other major target of retinoic acid (the acid form of vitamin A).[12][13][14] By so doing it induces cell differentiation and apoptosis and prevents the development of drug resistance.[15] It also has anti-angiogenic effects and inhibits cancer metastasis.[15] The retinoic acid receptors (RARs) regulate cell differentiation and proliferation whereas RXRs regulate apoptosis.[11]
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.[16]
The developer of bexarotene (brand name Targretin) was Ligand Pharmaceuticals, a San Diego biotech company which received FDA approval for the drug in 1999.[18] The FDA approved bexarotene on 29 December 1999.[19]
Japanese pharmaceutical Eisai bought the rights to Targretin and three other anti-cancer products from Ligand in 2006.[18] In the United States, patents on the drug expired in 2016.[18]
The results of CCMR-One, a clinical trial of the effects of bexarotene on patients with multiple sclerosis operated by the University of Cambridge,[28] have shown that the drug can cause remyelination, but will not lead to the drug being used as a therapy, due to its risk profile.[29]
^Gniadecki R, Assaf C, Bagot M, Dummer R, Duvic M, Knobler R, et al. (September 2007). "The optimal use of bexarotene in cutaneous T-cell lymphoma". The British Journal of Dermatology. 157 (3): 433–440. doi:10.1111/j.1365-2133.2007.07975.x. PMID17553039. S2CID33092727.
^Esteva FJ, Glaspy J, Baidas S, Laufman L, Hutchins L, Dickler M, et al. (March 2003). "Multicenter phase II study of oral bexarotene for patients with metastatic breast cancer". Journal of Clinical Oncology. 21 (6): 999–1006. doi:10.1200/JCO.2003.05.068. PMID12637463.
