Bexarotene and DAB(389)IL-2 (denileukin diftitox, ONTAK) in treatment of cutaneous T-cell lymphomas: algorithms.
Mycosis fungoides (MF), CD4(+) epidermotropic cutaneous T-cell lymphoma (CTCL), often arises as indolent, inflammatory, chronic, persistent patches and plaques. Conservative and sequential topical therapy patients have the same survival as patients treated with aggressive chemotherapy. Hence, until curative therapy is found, therapies that keep MF in check and prevent progression to more advanced lymphoma may be desirable alternatives and may preserve quality of life. Stage IA patients with stable disease have a very favorable prognosis and often initially receive psoriasis-type therapy. Bexarotene gel, a new topical retinoid X receptor retinoid will resolve MF lesions, reducing dermal T-cell infiltrates when used as a single agent. However, it may be even more effective when combined with topical steroids, with phototherapy (ultraviolet B and psoralen-ultraviolet A), or even with oral bexarotene. The gel may also provide a safe adjunctive therapy for individual lesions that are refractory to other agents, including keratodermas. When more than 10% of the body is involved with CTCL or when adenopathy is present (> stage IB), systemic therapy is indicated. Bexarotene capsules have the advantage of easy oral administration and are extremely effective both for early-stage patients with long-standing extensive plaques and for late-stage patients with Sézary syndrome or large-cell transformation. Monitoring of white blood cell count, lipids, and thyroid function is required. Bexarotene should be tested in combination with interferon-alfa or other therapies such as photopheresis, psoralen-ultraviolet A, and methotrexate and for maintenance after total body skin electron beam. DAB(389)IL-2 is targeted to CD25(+), the interleukin-2 receptor on activated T cells as measured by the expression of CD25. DAB(389)IL-2 has given complete or partial remission in 30% of highly refractory patients with extensive plaques and disfiguring tumors. Because it is effective in killing T cells that surround dermal vessels, cytokine release may occur and result in capillary leak syndrome. Hence, it will be reserved for more advanced and refractory patients and will require intravenous administration and monitoring. The use of oral bexarotene first to reduce dermal infiltrates prior to DAB(389)IL-2 administration might reduce subsequent side effects imparted by this therapy. With three new highly effective agents in the armamentarium for the treatment of CTCL, new combination treatment algorithms can be tested to achieve maximal benefit and quality of life for these patients.
Duvic
M
M
Dermatology Section, M.D. Anderson Cancer Center, Houston, TX 77030, USA. mduvic@mdanderson.org
D000465:Algorithms; D016588:Anticarcinogenic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077610:Bexarotene; D004167:Diphtheria Toxin / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000922:Immunotoxins / Q000009:adverse effects / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy*; D013764:Tetrahydronaphthalenes / Q000009:adverse effects / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D004167:Diphtheria Toxin; D007166:Immunosuppressive Agents; D000922:Immunotoxins; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D013764:Tetrahydronaphthalenes; C078456:denileukin diftitox; D000077610:Bexarotene