Systemic monotherapy vs combination therapy for CTCL: rationale and future strategies.
There are few approved therapies for cutaneous T-cell lymphoma (CTCL). The retinoids are the major biologic response modifiers used in CTCL, producing good response rates but few complete responses. For patients with early-stage disease, the oral retinoids can be combined with other therapies, such as psoralen plus ultraviolet A or interferon alpha, to improve response rates. Combined-modality therapy with oral retinoids, combined chemotherapy, electron-beam therapy, and topical mustargen has also proved effective. For the treatment of advanced-stage disease, the targeted therapy denileukin diftitox (Ontak) provides a nonimmunosuppressive alternative to conventional chemotherapy or radiation therapy. Of the conventional chemotherapies that have been tested in CTCL, gemcitabine (Gemzar) has demonstrated good efficacy in producing responses, particularly in patients with tumors. This agent can be used in combination with a maintenance therapy of bexarotene (Targretin) to manage the plaques and patches of mycosis fungoides. Several other targeted therapies are now also in testing, for example, alemtuzumab (CamPath), HuMax-CD4, several histone deacetylase inhibitors, and the transition-state inhibitor forodesine. These drugs, in combination with currently used therapies, may increase the number and combinations of therapies available for the treatment of this chronic condition to optimize long-lasting responses in CTCL.
Duvic
Madeleine
M
Department of Dermatology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA. mduvic@mdanderson.org
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant / Q000639:trends; D004167:Diphtheria Toxin / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy*; D008466:Mechlorethamine / Q000627:therapeutic use; D011684:Purine Nucleosides / Q000627:therapeutic use; D011744:Pyrimidinones / Q000627:therapeutic use; D018714:Radiotherapy, Adjuvant / Q000639:trends; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012176:Retinoids / Q000627:therapeutic use; D012751:Sezary Syndrome / Q000188:drug therapy; D012878:Skin Neoplasms / Q000188:drug therapy*; D000077337:Vorinostat
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D006877:Hydroxamic Acids; D007155:Immunologic Factors; D016898:Interferon-alpha; D007376:Interleukin-2; D011684:Purine Nucleosides; D011744:Pyrimidinones; D011993:Recombinant Fusion Proteins; D012176:Retinoids; C078456:denileukin diftitox; D000074323:Alemtuzumab; C113101:forodesine; D008466:Mechlorethamine; D000077337:Vorinostat