Recurrent Mycosis Fungoides and the Sézary Syndrome

Current Clinical Trials

The treatment of relapsed patients with cutaneous T-cell lymphomas involves the joint decisions of the dermatologist, medical oncologist, and radiation oncologist. It may be possible to re-treat localized areas of relapse in the skin with additional electron-beam radiation or possibly to repeat total-skin electron-beam radiation therapy (TSEB).[1] Photon radiation to bulky skin or nodal masses may prove beneficial. If these options are not possible, then continued topical treatment with other modalities such as mechlorethamine or psoralen and ultraviolet A radiation (PUVA) may be warranted to relieve cutaneous symptoms.

Clinical trials, if possible, should be considered as the next therapeutic option. Options under clinical evaluation include:[2,3]

• Additional electron-beam radiation or a repeat of TSEB.
• Photon radiation to bulky skin or nodal masses.
• Topical treatment with mechlorethamine or PUVA.
• PUVA combined with interferon-alpha-2a is associated with a high response rate.[4]
• Ultraviolet B radiation.
• Symptomatic management with topical corticosteroids.
• Extracorporeal photochemotherapy has produced tumor regression in patients resistant to other therapies.[5,6]
• Radioimmunotherapy using an I-131-labeled monoclonal antibody directed against a T-cell antigen has produced brief responses in a clinical trial.[7]
• The interleukin-2 fusion toxin, denileukin diftitox, is given monthly with response rates of about 30% to 40%.[3,8]
• Bexarotene is a retinoid available in an oral or topical form with activity in patients with recurrent MF, as evidenced in the LIGAND-L1069-20 trial.[9,10]
• New purine nucleoside phosphorylase inhibitors such as peldesine.[11]
• Allogeneic or autologous bone marrow transplantation.[12-14]
• Vorinostat or romidepsin (oral histone deacetylase inhibitors).[15,16]

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent 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. Becker M, Hoppe RT, Knox SJ: Multiple courses of high-dose total skin electron beam therapy in the management of mycosis fungoides. Int J Radiat Oncol Biol Phys 32 (5): 1445-9, 1995.  [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. 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]
   
   
4. 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]
   
   
5. 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]
   
   
6. Heald PW, Perez MI, McKiernan G, et al.: Extracorporeal photochemotherapy for CTCL. Prog Clin Biol Res 337: 443-7, 1990.  [PUBMED Abstract]
   
   
7. Rosen ST, Zimmer AM, Goldman-Leikin R, et al.: Radioimmunodetection and radioimmunotherapy of cutaneous T cell lymphomas using an 131I-labeled monoclonal antibody: an Illinois Cancer Council Study. J Clin Oncol 5 (4): 562-73, 1987.  [PUBMED Abstract]
   
   
8. 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]
   
   
9. Miller VA, Benedetti FM, Rigas JR, et al.: Initial clinical trial of a selective retinoid X receptor ligand, LGD1069. J Clin Oncol 15 (2): 790-5, 1997.  [PUBMED Abstract]
   
   
10. 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]
    
    
11. Henderson B, Poole S, Wilson M: Microbial/host interactions in health and disease: who controls the cytokine network? Immunopharmacology 35 (1): 1-21, 1996.  [PUBMED Abstract]
    
    
12. Molina A, Zain J, Arber DA, et al.: Durable clinical, cytogenetic, and molecular remissions after allogeneic hematopoietic cell transplantation for refractory Sezary syndrome and mycosis fungoides. J Clin Oncol 23 (25): 6163-71, 2005.  [PUBMED Abstract]
    
    
13. Duvic M, Donato M, Dabaja B, et al.: Total skin electron beam and non-myeloablative allogeneic hematopoietic stem-cell transplantation in advanced mycosis fungoides and Sezary syndrome. J Clin Oncol 28 (14): 2365-72, 2010.  [PUBMED Abstract]
    
    
14. Duarte RF, Canals C, Onida F, et al.: Allogeneic hematopoietic cell transplantation for patients with mycosis fungoides and Sézary syndrome: a retrospective analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 28 (29): 4492-9, 2010.  [PUBMED Abstract]
    
    
15. 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]
    
    
16. 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]