Stage II Mycosis Fungoides and the Sézary Syndrome
No curative therapy exists for patients with stage II disease. The choice of initial palliative therapy is, therefore, dependent on the patient’s symptoms and 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. 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. Maintenance therapy with PUVA is generally required to prolong remission duration.[3,4] 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 the skin alone can be treated without systemic effects. This therapy requires a radiation therapy facility with physics support, considerable technical expertise, and precise dosimetry. The therapy can provide excellent palliation with complete response rates of as much as 80%.[6-8]
- Ultraviolet B radiation is under clinical evaluation.
- Symptomatic management with topical corticosteroids.
- Topical mechlorethamine (nitrogen mustard). Topical application of mechlorethamine has produced regression of cutaneous lesions with particular efficacy in early stages of the disease. The overall complete remission rate is related to skin stage; 25% to 75% of TNM classification T2, and as many as 50% of T3 patients have complete responses. Treatments are usually continued for 2 to 3 years.[6,9-11]
- Local electron-beam radiation or orthovoltage radiation therapy may also be used to palliate areas of bulky or symptomatic disease.
- Interferon-alpha alone or in combination with topical therapy, as evidenced in the ECOG-1495 trial.
- Bexarotene, an oral or topical retinoid.[13,14]
- Oral methotrexate.
- Pegylated liposomal doxorubicin.[16,17]
- Vorinostat or romidepsin (oral histone deacetylase inhibitors).[18,19]
- Denileukin diftitox (interleukin-2 fused with diphtheria toxin).
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II 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
- 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]
- Querfeld C, Rosen ST, Kuzel TM, et al.: Long-term follow-up of patients with early-stage cutaneous T-cell lymphoma who achieved complete remission with psoralen plus UV-A monotherapy. Arch Dermatol 141 (3): 305-11, 2005. [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]
- Chinn DM, Chow S, Kim YH, et al.: Total skin electron beam therapy with or without adjuvant topical nitrogen mustard or nitrogen mustard alone as initial treatment of T2 and T3 mycosis fungoides. Int J Radiat Oncol Biol Phys 43 (5): 951-8, 1999. [PUBMED Abstract]
- Quirós PA, Jones GW, Kacinski BM, et al.: Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides). Int J Radiat Oncol Biol Phys 38 (5): 1027-35, 1997. [PUBMED Abstract]
- Ysebaert L, Truc G, Dalac S, et al.: Ultimate results of radiation therapy for T1-T2 mycosis fungoides (including reirradiation). Int J Radiat Oncol Biol Phys 58 (4): 1128-34, 2004. [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]
- Hoppe RT, Abel EA, Deneau DG, et al.: Mycosis fungoides: management with topical nitrogen mustard. J Clin Oncol 5 (11): 1796-803, 1987. [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]
- 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]
- 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]
- 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]
- 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]
- 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]