Stage III Mycosis Fungoides and the Sézary Syndrome
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. In patients with the Sézary syndrome (SS), a high probability of extracutaneous involvement exists, and therefore systemic chemotherapy is often given, though no proof is available that this affects survival.
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. In the latter group, combination chemotherapy was reserved for symptomatic extracutaneous disease or for disease refractory to topical therapies. Patients of 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.[Level of evidence: 1iiA]
- 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. PUVA combined with interferon-alpha-2a is associated with a high response rate.
- 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]
- Ultraviolet B radiation is under clinical evaluation.
- Symptomatic management with topical corticosteroids.
- Local electron-beam radiation or orthovoltage radiation therapy may also be used to palliate areas of bulky or symptomatic disease.
- Fludarabine, 2-chlorodeoxyadenosine, and pentostatin are active agents for mycosis fungoides (MF) and SS.[8-11]
- Interferon-alpha alone or in combination with topical therapy, as evidenced in ECOG-1495.[9,12]
- Denileukin diftitox (interleukin-2 fused with diphtheria toxin).[13-15]
- Systemic chemotherapy (single agent or combination) often combined with treatment directed at the skin.[2,16,17]
- Extracorporeal photochemotherapy.[18-20]
- 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.[21,22]
- Bexarotene, an oral or topical retinoid.[23,24]
- Pegylated liposomal doxorubicin.[25,26]
- Vorinostat or romidepsin (oral histone deacetylase inhibitors).[1,27,28]
- Alemtuzumab (a humanized monoclonal antibody targeting the CD52 antigen).
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
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Reddy S, Parker CM, Shidnia H, et al.: Total skin electron beam radiation therapy for mycosis fungoides. Am J Clin Oncol 15 (2): 119-24, 1992. [PUBMED Abstract]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Siegel RS, Pandolfino T, Guitart J, et al.: Primary cutaneous T-cell lymphoma: review and current concepts. J Clin Oncol 18 (15): 2908-25, 2000. [PUBMED Abstract]
- 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]
- Rosen ST, Foss FM: Chemotherapy for mycosis fungoides and the Sézary syndrome. Hematol Oncol Clin North Am 9 (5): 1109-16, 1995. [PUBMED Abstract]
- 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]
- 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]
- Heald PW, Perez MI, McKiernan G, et al.: Extracorporeal photochemotherapy for CTCL. Prog Clin Biol Res 337: 443-7, 1990. [PUBMED Abstract]
- 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]
- Vonderheid EC, Tan ET, Kantor AF, et al.: Long-term efficacy, curative potential, and carcinogenicity of topical mechlorethamine chemotherapy in cutaneous T cell lymphoma. J Am Acad Dermatol 20 (3): 416-28, 1989. [PUBMED Abstract]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]