Opinion statement
Treatment of mycosis fungoides (MF) is indicated to reduce symptoms, improve clinical appearance, prevent secondary complications, and prevent progression of disease, all of which may have an impact on survival. Treatment of MF includes topical and systemic therapies, which can be administered alone or in combination. Psoralen and ultraviolet A radiation is effective in early-stage MF, inducing complete remissions in most patients. Psoralen and ultraviolet A radiation may also be combined with low doses of interferon (IFN)-a to treat stage I/II disease. However, early aggressive therapy with radiation and chemotherapy does not improve the prognosis. Local radiotherapy or total skin electron beam irradiation has been used with success to control advanced skin disease. Extracorporeal photopheresis may also be used successfully, but it is not generally available. Once the disease becomes refractory to topical therapy, IFN-a single-agent or combination chemotherapy may be administered, but the duration of response is often less than 1 year and ultimately all patients will relapse and become refractory. Among chemotherapeutic agents, pentostatin, gemcitabine, and liposomal doxorubicin seem to be particularly effective. Response rates after combined modality therapy with total skin electron beam irradiation and chemotherapy/IFN-a appear similar to response rates of chemotherapy alone. Therefore, there is a great need for the further development of novel emerging treatment modalities, such as retinoids (ie, bexarotene) and immunotherapeutic agents (ie, cytokines, tumor vaccines, and monoclonal antibodies), all of which appear to have significant therapeutic potential in patients with MF. Biologically based therapies may reduce the need for genotoxic therapies, such as cytostatics and radiotherapy.
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References and Recommended Reading
Smoller BR, Bishop K, Glusac E, et al.: Reassessment of histologic parameters in the diagnosis of mycosis fungoides. Am J Surg Pathol 1995, 19:1423–1430.
Tensen CP, Flier J, Van Der Raaij-Helmer EM, et al.: Human IP-9: a keratinocyte-derived high affinity CXCchemokine ligand for the IP-10/Mig receptor (CXCR3). J Invest Dermatol 1999, 112:716–722.
Kakinuma T, Sugaya M, Nakamura K, et al.: Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides: serum TARC levels reflect the disease activity of mycosis fungoides. J Am Acad Dermatol 2003, 48:23–30.
Rook A, Heald P: The immunopathogenesis of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 1995, 9:997–1010.
DeVita V, Hellman S, Rosenberg SA: Cancer: Principles and Practice of Oncology. Philadelphia: Lippincott Williams & Wilkins; 2001.
Bunn PA Jr, Lamberg SI: Report of the Committee on Staging and Classification of Cutaneous T-Cell Lymphomas. Cancer Treat Rep 1979, 63:725–728.
van Doorn R, Van Haselen CW, van Voorst Vader PC, et al.: Mycosis fungoides: disease evolution and prognosis of 309 Dutch patients. Arch Dermatol 2000, 136:504–510. A multivariate analysis on prognostic factors in MF and survival rates in different stages of MF.
Zackheim HS: Treatment of mycosis fungoides/Sezary syndrome: the University of California, San Francisco (UCSF) approach. Int J Dermatol 2003, 42:53–56.
Esteve E, Bagot M, Joly P, et al.: A prospective study of cutaneous intolerance to topical mechlorethamine therapy in patients with cutaneous T-cell lymphomas. French Study Group of Cutaneous Lymphomas. Arch Dermatol 1999, 135:1349–1353.
Foulc P, Evrard V, Dalac S, et al.: Evaluation of a 1-h exposure time to mechlorethamine in patients undergoing topical treatment. Br J Dermatol 2002, 147:926–930.
Liu HL, Kim YH: Bexarotene gel: a Food and Drug Administration-approved skin-directed therapy for early-stage cutaneous T-cell lymphoma. Arch Dermatol 2002, 138:398–399.
Heald P, Mehlmauer M, Martin AG, et al.: Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. J Am Acad Dermatol 2003, 49:801–815. A large phase III trial on topical bexarotene therapy in MF.
Herrmann JJ, Roenigk HH Jr, Hurria A, et al.: Treatment of mycosis fungoides with photochemotherapy (PUVA): long-term follow-up. J Am Acad Dermatol 1995, 33:234–242.
Edelson R, Berger C, Gasparro F, et al.: Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy: preliminary results. N Engl J Med 1987, 316:297–303.
Fritz TM, Kleinhans M, Nestle FO, et al.: Combination treatment with extracorporeal photopheresis, interferon alfa and interleukin-2 in a patient with the Sezary syndrome. Br J Dermatol 1999, 140:1144–1147.
Micaily B, Miyamoto C, Kantor G, et al.: Radiotherapy for unilesional mycosis fungoides. Int J Radiat Oncol Biol Phys 1998, 42:361–364.
Hoppe RT, Cox RS, Fuks Z, et al.: Electron-beam therapy for mycosis fungoides: the Stanford University experience. Cancer Treat Rep 1979, 63:691–700.
Wilson LD, Licata AL, Braverman IM, et al.: Systemic chemotherapy and extracorporeal photochemotherapy for T3 and T4 cutaneous T-cell lymphoma patients who have achieved a complete response to total skin electron beam therapy. Int J Radiat Oncol Biol Phys 1995, 32:987–995.
Wilson LD, Jones GW, Kim D, et al.: Experience with total skin electron beam therapy in combination with extracorporeal photopheresis in the management of patients with erythrodermic (T4) mycosis fungoides. J Am Acad Dermatol 2000, 43:54–60.
Jones GW, Kacinski BM, Wilson LD, et al.: Total skin electron radiation in the management of mycosis fungoides: Consensus of the European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Project Group. J Am Acad Dermatol 2002, 47:364–370. A consensus report on electron radiation in MF.
Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 1995, 9:1089–1107.
Stadler R, Otte HG, Luger T, et al.: Prospective randomized multicenter clinical trial on the use of interferon-2a plus acitretin versus interferon-2a plus PUVA in patients with cutaneous T-cell lymphoma stages I and II. Blood 1998, 92:3578–3581. An important randomized trial involving IFN and PUVA in combination that allows the use of a lower dosage of both therapies, reducing the adverse events associated with each and increasing the response rate.
Winkelmann RK, Diaz-Perez JL, Buechner SA: The treatment of Sezary syndrome. J Am Acad Dermatol 1984, 10:1000–1004.
Zackheim HS, Kashani-Sabet M, Hwang ST: Low-dose methotrexate to treat erythrodermic cutaneous T-cell lymphoma: results in twenty-nine patients. J Am Acad Dermatol 1996, 34:626–631.
Akpek G, Koh HK, Bogen S, et al.: Chemotherapy with etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone in patients with refractory cutaneous T-cell lymphoma. Cancer 1999, 86:1368–1376.
Muche JM, Gellrich S, Sterry W: Treatment of cutaneous T-cell lymphomas. Semin Cutan Med Surg 2000, 19:142–148.
Wollina U, Graefe T, Karte K: Treatment of relapsing or recalcitrant cutaneous T-cell lymphoma with pegylated liposomal doxorubicin. J Am Acad Dermatol 2000, 42:40–46.
Wollina U, Dummer R, Brockmeyer NH, et al.: Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer 2003, 98:993–1001. An important study on pegylated liposomal doxorubicin, which is a new drug for MF.
Ho AD, Suciu S, Stryckmans P, et al.: Pentostatin in T-cell malignancies: a phase II trial of the EORTC. Leukemia Cooperative Group. Ann Oncol 1999, 10:1493–1498.
Kurzrock R, Pilat S, Duvic M: Pentostatin therapy of Tcell lymphomas with cutaneous manifestations. J Clin Oncol 1999, 17:3117–3121. In this trial, escalating doses of pentostatin were used in patients with relapsed CTCL, with an OR rate of 71%.
Scarisbrick JJ, Child FJ, Clift A, et al.: A trial of fludarabine and cyclophosphamide combination chemotherapy in the treatment of advanced refractory primary cutaneous T-cell lymphoma. Br J Dermatol 2001, 144:1010–1015.
Zinzani PL, Baliva G, Magagnoli M, et al.: Gemcitabine treatment in pretreated cutaneous T-cell lymphoma: experience in 44 patients. J Clin Oncol 2000, 18:2603–2606. A major trial regarding gemcitabine, which has promising activity and is well tolerated in CTCL.
Sallah S, Wan JY, Nguyen NP: Treatment of refractory Tcell malignancies using gemcitabine. Br J Haematol 2001, 113:185–187.
Zhang C, Hazarika P, Ni X, et al.: Induction of apoptosis by bexarotene in cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action. Clin Cancer Res 2002, 8:1234–1240.
Duvic M, Martin AG, Kim Y, et al.: Phase II and III clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous Tcell lymphoma. Arch Dermatol 2001, 137:581–593. An important trial regarding bexarotene in early-stage CTCL.
Duvic M, Hymes K, Heald P, et al.: Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II/III trial results. J Clin Oncol 2001, 19:2456–2471. A large phase II/III trial regarding bexarotene in advancedstage CTCL.
Talpur R, Ward S, Apisarnthanarax N, et al.: Optimizing bexarotene therapy for cutaneous T-cell lymphoma. J Am Acad Dermatol 2002, 47:672–684.
Lundin J, Hagberg H, Repp R, et al.: Phase II study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome. Blood 2003, 101:4267–4272. This study verifies that alemtuzumab is highly active in CTCL.
Kennedy GA, Seymour JF, Wolf M, et al.: Treatment of patients with advanced mycosis fungoides and Sezary syndrome with alemtuzumab. Eur J Haematol 2003, 71:250–256.
Knox S, Hoppe RT, Maloney D, et al.: Treatment of cutaneous T-cell lymphoma with chimeric anti-CD4 monoclonal antibody. Blood 1996, 87:893–899.
Obitz E, Kim H, Iversen L, et al.: HuMaX-CD4, A fully human monoclonal antibody: early results of an ongoing phase II trial in cutaneous T-cell lymphoma (CTCL) [abstract]. Blood 2003, 102:645a This paper involves a potential emerging drug in CTCL.
Olsen E, Duvic M, Frankel A, et al.: Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. J Clin Oncol 2001, 19:376–388.
Foss FM, Bacha P, Osann KE, et al.: Biological correlates of acute hypersensitivity events with DAB(389)IL-2 (denileukin diftitox, ONTAK) in cutaneous T-cell lymphoma: decreased frequency and severity with steroid premedication. Clin Lymphoma 2001, 1:298–302. Steroids improved response and reduced toxicity in patients with MF who were treated with denileukin diftitox.
Donato M, Kurzrock R, Champlin R, et al.: Complete remission at late-stage mycosis fungoides/Sezary syndrome following allogeneic transplantation. Blood 2003, 102:731a.
Molina A, Zain J, Arber D, et al.: Is allogeneic hematopoietic stem cell transplantation (AHSCT) potentially curative in a group of refractory cutaneous T-cell lymphomas (CTCLs)? Durable clinical, cytogenetic and molecular remissions after AHSCT for refractory Sezary syndrome and mycosis fungoides. Blood 2003, 102:476a.
Kaplan EH, Rosen ST, Norris DB, et al.: Phase II study of recombinant human interferon gamma for treatment of cutaneous T-cell lymphoma. J Natl Cancer Inst 1990, 82:208–212.
Duvic M, Talpur R, Chiao N, Chiao J: Phase II trial of oral suberoylanilide hydroxamic acid (SAHA) for cutaneous T-cell lymphoma (CTCL) and peripheral Tcell lymphoma (PTCL). Blood 2003, 102:179a. This paper involves a potential future agent in CTCL.
Rook AH, Wood GS, Yoo EK, et al.: Interleukin-12 therapy of cutaneous T-cell lymphoma induces lesion regression and cytotoxic T-cell responses. Blood 1999, 94:902–908.
Rook AH, Zaki MH, Wysocka M, et al.: The role for interleukin-12 therapy of cutaneous T-cell lymphoma. Ann N Y Acad Sci 2001, 941:177–184.
Maier T, Tun-Kyi A, Tassis A, et al.: Vaccination of patients with cutaneous T-cell lymphoma using intranodal injection of autologous tumor-lysate-pulsed dendritic cells. Blood 2003, 102:2338–2344. This paper describes an entirely new therapeutic principle in CTCL.
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Lundin, J., Österborg, A. Therapy for mycosis fungoides. Curr. Treat. Options in Oncol. 5, 203–214 (2004). https://doi.org/10.1007/s11864-004-0012-8
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DOI: https://doi.org/10.1007/s11864-004-0012-8