Topical and systemic retinoid therapy for cutaneous T-cell lymphoma

Because curative therapies for CTCL are not yet available, short of TSEB in patients who have early-stage disease and allogeneic bone marrow transplantation in patients who have more advanced disease, the goal of current therapies is to prevent progression of MF and to preserve quality of life. The overall conclusion drawn from the studies reported in the literature, is that retinoids as monotherapy, or in combination with other nonaggressive treatment modalities, represent a low-risk treatment alternative that is especially suitable for controlling early stages of MF and other CTCL. A combination of therapies may be more effective in controlling CTCL as shown with IFN-alpha plus retinoids, and, recently, IFN-alpha with bexarotene and other modalities. For example, isotretinoin, followed by TSEB (for stage I to II disease) or preceded by chemotherapy (for stage II and IV disease) and bexarotene plus PUVA or photopheresis plus IFN, gave overall response rates of 82% and 69% in patients who had MF and SS, respectively. Retinoids as monotherapy may induce complete remissions, but usually these responses are of short duration and relapses are common. Clinical response is not identical to histologic clearance. Even in cases with clinically complete clearance of skin lesions, lymphoid infiltrates persisted, which are most likely the source of recurrences. The new generation of retinoids, the RXR selective agonists like bexarotene, represent a promising approach for refractory or persistent MF that is unresponsive to first-line therapies. Individual differences in response to retinoids may be due to different expression of retinoid receptors, functional polymorphisms in metabolizing retinoids, or resistance to some retinoids. In the future, pharmacogenomic studies are needed to clarify the mechanisms that underlie the differing response rates of patients who have CTCL to retinoids. In addition, new agonists of RAR and RXR, either selective or pan agonists, will become available and will enlarge the spectrum of vitamin A analogs that have antitumoral properties.