Bexarotene (Agonist at the Retinoid X Receptor)

Bexarotene is a synthetic retinoid analogue which belongs to a group of compounds called rexinoids.¹ It has a role in the regulation of cell differentiation and proliferation. It is well tolerated when given by mouth and as it is associated with little myelosuppression or immunosuppression, it is an excellent candidate for combination therapy with other treatments. Bexarotene can cause regression of cutaneous T-cell lymphoma (CTCL).

Initial assessment should include repeated skin biopsies (ellipse rather than punch) to confirm the diagnosis.

• Histology, immunophenotypic, and preferably T-cell receptor (TCR) gene analysis should be performed on all tissue samples.
• All patients (with the possible exception of early stage mycosis fungoides [stage IA] and lymphomatoid papulosis) should ideally be reviewed by an appropriate multidisciplinary team (MDT) for confirmation of the diagnosis and to establish a management strategy.
• Initial staging computed tomography (CT) scans are required in all patients with the exception of those with early stages of mycosis fungoides (stage IA/IB) and lymphomatoid papulosis.
• At diagnosis peripheral blood samples should be analysed for total white cell, lymphocyte, and Sezary cell counts, serum lactate dehydrogenase (LDH), liver and renal function, lymphocyte subsets, CD4/CD8 ratios, human T-cell lymphotropic virus (HTLV)-I serology and, preferably, TCR gene analysis.
• Bone marrow aspirate or trephine biopsies are required for CTCL variants (with the exception of lymphomatoid papulosis) and may also be appropriate for those with late stages of mycosis fungoides (stage IIB or above).
• The histology, after correlation with the clinical features, should be classified according to an integration of the World Health Organization (WHO) and European Organization for Research and Treatment of Cancer (EORTC classification).^2,3

Bexarotene (Targretin®) is used as systemic second-line therapy in Europe and the USA, for all stages up to Stage IVB.
However a recent pilot trial evaluating its efficacy, found significant adverse effects (hypertriglyceridaemia, risk of pancreatitis, hypothyroidism and haematological reactions such as leukopenia and anemia). They concluded that, weighing benefits and risks, bexarotene could not be recommended as standard therapy at present.⁴There have also been reports of adverse outcomes in Sezary syndrome (for example rapid onset of CD8 aggressive T-cell lymphoma) during bexarotene therapy.⁵

• Bexarotene gel 1% has been used with narrowband UVB (NBUVB) phototherapy for moderate to severe psoriasis. Based on analysis of target lesion scores, bexarotene gel 1% with NBUVB was found to be significantly more effective than placebo with NBUVB.⁶
• It has been reported that bexarotene prevented and overcame acquired drug resistance in advanced breast cancer and non-small cell lung cancer. These reports may have been optimistic looking at results from the SPIRIT I and II trials.⁷
• There may also be a role for bexarotene in combination with chemotherapeutic agents in prevention and overcoming acquired drug resistance in advanced prostate cancer.⁸