The optimal use of bexarotene in cutaneous T-cell lymphoma

Abstract

The management goal in cutaneous T-cell lymphomas (CTCLs) is to improve symptoms and induce remission. Early-stage disease is generally treated with skin-directed therapies. However, if these do not control the disease, systemic therapy becomes necessary. Bexarotene, a novel rexinoid, is an oral, noncytotoxic drug that has been approved in Europe for the treatment of refractory advanced-stage CTCL and in the U.S.A. for refractory CTCL. We provide guidance on the use of bexarotene in the management of CTCL, based on data from phase II/III clinical trials and the authors' clinical experience, and suggest how the potential of the drug can be maximized. The clinical trial results with bexarotene are reviewed, especially in comparison with interferon-alpha, which is the other commonly used noncytotoxic systemic therapy for CTCL. A treatment algorithm for bexarotene in refractory CTCL is suggested. As bexarotene may take time to achieve a maximum response, this algorithm recommends that therapy should be continued for a sufficient period to allow for a delayed onset of action. In addition, possible combination therapies with bexarotene are discussed. We conclude that bexarotene is effective in the management of CTCL, and has the advantage of oral administration. An on-going randomized clinical trial comparing psoralen plus ultraviolet A (PUVA) with PUVA plus bexarotene will provide valuable information about this combination regimen in early-stage disease, but further data are needed on the relative efficacies of other combination therapies with bexarotene in CTCL.

Retinoid X Receptor-selective Signaling in the Regulation of Akt/Protein Kinase B Isoform-specific Expression

“…Bexarotene is an RXR-selective ligand that has been approved by the Food and Drug Administration for use in the treatment of refractory or persistent cutaneous T-cell lymphoma, and it has been shown to reduce tumor growth in several additional cancers as well (20,21). Moreover, bexarotene is an efficient enhancer for the specification of skeletal muscle lineage (22).…”

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

“…In one retrospective study, all patients treated with bexarotene developed hyperlipidemia and hypothyroidism, frequently within weeks of initiating treatment [228]. Consequently, use of lipid-lowering agents (e.g., statins or fenofibrate but not gemfibrozil due to its association with increased bexarotene levels and pancreatitis) and low-dose levothyroxine (e.g., 50 lg) before initiating bexarotene is reasonable [229,230]. In clinical practice, bexarotene is frequently initiated at a lower dose of 150 mg/m 2 and subsequently titrated to full doses after 2-4 weeks of therapy, depending on patient tolerability.…”

How I treat mycosis fungoides and Sézary syndrome

“…[51][52][53] Time to response is in the order of weeks, and it can be combined with PUVA, chemotherapy, retinoids, and bexarotene. 30,31,41,42,46,50,54,55 In advanced-stage disease, our preference is to use single-agent IFN-␣ first, adding PUVA if there is more widespread pruritus and adding bexarotene if the response is suboptimal. Prolonged responses have also been observed with ␥-interferon.…”

“…Bexarotene may also be useful in maintaining responses after SDT. 46,[48][49][50] Topical bexarotene is particularly useful for patients who have a limited number of patches or plaques, and we recommend its use before topical chemotherapy. 47 In general terms, bexarotene is being used more frequently in MF/SS, often in place of the earlier generation retinoids.…”