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Mycosis Fungoides and the Sézary Syndrome Treatment (PDQ®)

Health Professional Version
Last Modified: 01/24/2014

Stage III Mycosis Fungoides

Current Clinical Trials

No curative treatment exists for patients with stage III disease. The initial choice of palliative therapy is, therefore, dependent on the local expertise with each modality.

A randomized study of 103 patients compared combined total-skin electron-beam radiation (TSEB) plus combination chemotherapy with conservation therapy consisting of sequential topical therapies.[1] In the latter group, combination chemotherapy was reserved for symptomatic extracutaneous disease or for disease refractory to topical therapies. Patients with any stage were eligible. Although the complete response rate was higher with combined therapy, toxic effects were considerably greater, and no difference was seen in disease-free or overall survival between the two groups.[1][Level of evidence: 1iiA]

Treatment options (note that in this clinical setting, the skin is easily injured; any of the topical therapies must be administered with extreme caution):[2,3]

  1. Psoralen and ultraviolet A radiation (PUVA). Therapeutic trials with PUVA have shown a 62% to 90% complete remission rate with early cutaneous stages achieving the best responses. PUVA may be used in conjunction with systemic treatment. Maintenance therapy with PUVA is generally required to prolong remission duration.[4] PUVA combined with interferon alpha-2a is associated with a high response rate.[5]

  2. TSEB. Electron radiation of appropriate energies will penetrate only to the dermis, and thus the skin alone can be treated without systemic effects. This therapy requires an excellent radiation therapy facility with physics support, considerable technical expertise, and precise dosimetry. The therapy can produce excellent palliation with complete response rates of as much as 80%.[6,7]

  3. Ultraviolet B radiation is under clinical evaluation.

  4. Symptomatic management with topical corticosteroids.

  5. Local electron-beam radiation or orthovoltage radiation therapy may also be used to palliate areas of bulky or symptomatic disease.[8]

  6. Fludarabine, 2-chlorodeoxyadenosine, and pentostatin are active agents for mycosis fungoides and SS.[9-12]

  7. Interferon-alpha alone or in combination with topical therapy, as evidenced in ECOG-1495.[10,13]

  8. Denileukin diftitox (interleukin-2 fused with diphtheria toxin).[14-16]

  9. Systemic chemotherapy (single agent or combination) often combined with treatment directed at the skin.[1,17,18]

  10. Extracorporeal photochemotherapy.[19-21]

  11. Topical mechlorethamine (nitrogen mustard). This form of treatment may be used palliatively or to supplement therapeutic approaches directed against nodal or visceral disease. The overall complete remission rate of TNM classification T4 patients is 20% to 40%. Treatments are usually continued for 2 to 3 years.[22,23]

  12. Bexarotene, an oral or topical retinoid.[24,25]

  13. Oral methotrexate (NCT00425555).[26]

  14. Pegylated liposomal doxorubicin.[27-29]

  15. Vorinostat or romidepsin or other histone deacetylase inhibitors.[3,30-32]

  16. Pralatrexate (folate analog).[33]

  17. Alemtuzumab (a humanized monoclonal antibody targeting the CD52 antigen).[3]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III mycosis fungoides/Sezary syndrome. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References
  1. Kaye FJ, Bunn PA Jr, Steinberg SM, et al.: A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides. N Engl J Med 321 (26): 1784-90, 1989.  [PUBMED Abstract]

  2. Trautinger F, Knobler R, Willemze R, et al.: EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome. Eur J Cancer 42 (8): 1014-30, 2006.  [PUBMED Abstract]

  3. Olsen EA, Rook AH, Zic J, et al.: Sézary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC). J Am Acad Dermatol 64 (2): 352-404, 2011.  [PUBMED Abstract]

  4. Herrmann JJ, Roenigk HH Jr, Hurria A, et al.: Treatment of mycosis fungoides with photochemotherapy (PUVA): long-term follow-up. J Am Acad Dermatol 33 (2 Pt 1): 234-42, 1995.  [PUBMED Abstract]

  5. Kuzel TM, Roenigk HH Jr, Samuelson E, et al.: Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome. J Clin Oncol 13 (1): 257-63, 1995.  [PUBMED Abstract]

  6. Jones GW, Rosenthal D, Wilson LD: Total skin electron radiation for patients with erythrodermic cutaneous T-cell lymphoma (mycosis fungoides and the Sézary syndrome). Cancer 85 (9): 1985-95, 1999.  [PUBMED Abstract]

  7. Navi D, Riaz N, Levin YS, et al.: The Stanford University experience with conventional-dose, total skin electron-beam therapy in the treatment of generalized patch or plaque (T2) and tumor (T3) mycosis fungoides. Arch Dermatol 147 (5): 561-7, 2011.  [PUBMED Abstract]

  8. Thomas TO, Agrawal P, Guitart J, et al.: Outcome of patients treated with a single-fraction dose of palliative radiation for cutaneous T-cell lymphoma. Int J Radiat Oncol Biol Phys 85 (3): 747-53, 2013.  [PUBMED Abstract]

  9. Saven A, Carrera CJ, Carson DA, et al.: 2-Chlorodeoxyadenosine: an active agent in the treatment of cutaneous T-cell lymphoma. Blood 80 (3): 587-92, 1992.  [PUBMED Abstract]

  10. Foss FM, Ihde DC, Breneman DL, et al.: Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol 10 (12): 1907-13, 1992.  [PUBMED Abstract]

  11. Foss FM, Ihde DC, Linnoila IR, et al.: Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol 12 (10): 2051-9, 1994.  [PUBMED Abstract]

  12. Kurzrock R, Pilat S, Duvic M: Pentostatin therapy of T-cell lymphomas with cutaneous manifestations. J Clin Oncol 17 (10): 3117-21, 1999.  [PUBMED Abstract]

  13. Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 9 (5): 1089-107, 1995.  [PUBMED Abstract]

  14. Prince HM, Martin AG, Olsen EA, et al.: Denileukin diftitox for the treatment of CD25 low-expression mycosis fungoides and Sézary syndrome. Leuk Lymphoma 54 (1): 69-75, 2013.  [PUBMED Abstract]

  15. 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 19 (2): 376-88, 2001.  [PUBMED Abstract]

  16. Prince HM, Duvic M, Martin A, et al.: Phase III placebo-controlled trial of denileukin diftitox for patients with cutaneous T-cell lymphoma. J Clin Oncol 28 (11): 1870-7, 2010.  [PUBMED Abstract]

  17. Rosen ST, Foss FM: Chemotherapy for mycosis fungoides and the Sézary syndrome. Hematol Oncol Clin North Am 9 (5): 1109-16, 1995.  [PUBMED Abstract]

  18. Zackheim HS, Epstein EH Jr: Low-dose methotrexate for the Sézary syndrome. J Am Acad Dermatol 21 (4 Pt 1): 757-62, 1989.  [PUBMED Abstract]

  19. Edelson R, Berger C, Gasparro F, et al.: Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med 316 (6): 297-303, 1987.  [PUBMED Abstract]

  20. Heald PW, Perez MI, McKiernan G, et al.: Extracorporeal photochemotherapy for CTCL. Prog Clin Biol Res 337: 443-7, 1990.  [PUBMED Abstract]

  21. Scarisbrick JJ, Taylor P, Holtick U, et al.: U.K. consensus statement on the use of extracorporeal photopheresis for treatment of cutaneous T-cell lymphoma and chronic graft-versus-host disease. Br J Dermatol 158 (4): 659-78, 2008.  [PUBMED Abstract]

  22. Lessin SR, Duvic M, Guitart J, et al.: Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol 149 (1): 25-32, 2013.  [PUBMED Abstract]

  23. de Quatrebarbes J, Estève E, Bagot M, et al.: Treatment of early-stage mycosis fungoides with twice-weekly applications of mechlorethamine and topical corticosteroids: a prospective study. Arch Dermatol 141 (9): 1117-20, 2005.  [PUBMED Abstract]

  24. 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 19 (9): 2456-71, 2001.  [PUBMED Abstract]

  25. 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 49 (5): 801-15, 2003.  [PUBMED Abstract]

  26. Zackheim HS, Kashani-Sabet M, McMillan A: Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol 49 (5): 873-8, 2003.  [PUBMED Abstract]

  27. Dummer R, Quaglino P, Becker JC, et al.: Prospective international multicenter phase II trial of intravenous pegylated liposomal doxorubicin monochemotherapy in patients with stage IIB, IVA, or IVB advanced mycosis fungoides: final results from EORTC 21012. J Clin Oncol 30 (33): 4091-7, 2012.  [PUBMED Abstract]

  28. Wollina U, Dummer R, Brockmeyer NH, et al.: Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer 98 (5): 993-1001, 2003.  [PUBMED Abstract]

  29. Quereux G, Marques S, Nguyen JM, et al.: Prospective multicenter study of pegylated liposomal doxorubicin treatment in patients with advanced or refractory mycosis fungoides or Sézary syndrome. Arch Dermatol 144 (6): 727-33, 2008.  [PUBMED Abstract]

  30. Duvic M, Dummer R, Becker JC, et al.: Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer 49 (2): 386-94, 2013.  [PUBMED Abstract]

  31. Olsen EA, Kim YH, Kuzel TM, et al.: Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol 25 (21): 3109-15, 2007.  [PUBMED Abstract]

  32. Piekarz RL, Frye R, Turner M, et al.: Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27 (32): 5410-7, 2009.  [PUBMED Abstract]

  33. Horwitz SM, Kim YH, Foss F, et al.: Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 119 (18): 4115-22, 2012.  [PUBMED Abstract]