A Randomized Trial Comparing Combination Electron-Beam Radiation and Chemotherapy with Topical Therapy in the Initial Treatment of Mycosis Fungoides

Abstract

Mycosis fungoides is a T-cell lymphoma that arises in the skin and progresses at highly variable rates. Nonradomized studies have suggested that early aggressive therapy may improve the prognosis in this usually fatal disease. We studied 103 patients with mycosis fungoides, who, after complete staging, were randomly assigned to receive either combination therapy, consisting of 3000 cGy of electron-beam radiation to the skin combined with parenteral chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine (n = 52) or sequential topical treatment (n = 51). The prognostic factors were well balanced in the two groups. Combined therapy produced considerable toxicity: 12 patients required hospitalization for fever and transient neutropenia, 5 had congestive heart failure, and 2 were later found to have acute nonlymphocytic leukemia. Patients receiving combined therapy had a significantly higher rate of complete response, documented by biopsy, than patients receiving conservative therapy (38 percent vs. 18 percent; P = 0.032). After a median follow-up of 75 months, however, there was no significant difference between the treatment groups in disease-free or overall survival. We conclude that early aggressive therapy with radiation and chemotherapy does not improve the prognosis for patients with mycosis fungoides as compared with conservative treatment beginning with sequential topical therapies.

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome

“…92,93 Gastrointestinal toxicity has been frequently noted, usually within 2 h of BCNU administration, and renal dysfunction has been reported in patients exposed to large cumulative doses. 95 96 The combination therapy achieved a significantly higher CR rate but at the expense of considerable toxicity. Importantly, after a median follow-up of 75 months, there was no difference between the treatment groups in terms of PFS or overall survival.…”

“…Importantly, after a median follow-up of 75 months, there was no difference between the treatment groups in terms of PFS or overall survival. 96 Hence, aggressive treatment with radiation and chemotherapy does not improve prognosis in patients with early-stage MF compared with those treated with standard SDT. 96 The EORTC Workshop meeting recommended that systemic chemotherapy should not be used at this disease stage.…”

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

“…For many patients, this may involve either expectant management (i.e., ''watch and wait'') or skin-directed therapies. A randomized trial comparing early combined modality therapy with both radiation and multiagent chemotherapy (cyclophosphamide, doxorubicin, etoposide, and vincristine) with sequential topical therapies demonstrated that combined modality therapy, while associated with a superior complete response rate, did not translate into improvements in disease-free or overall survival, but was associated with significant toxicity [198]. Therefore, patients with limited-stage disease who require therapy are best approached with skin-directed therapies, usually under the direction of a dermatologist and/or radiation oncologist.…”

“…As for limited-stage disease, multiagent chemotherapy, with only few exceptions, is generally not appropriate [198]. As summarized in Fig.…”

Non-Hodgkin's Lymphomas (NHL)

“…A randomized study between TSEBI plus concurrent chemotherapy and local skin treatment with mustin found, at early stages. no difference in the rates of remission or relapse-free survival in either arm of the study (146). A pilot study of TSEBI combined with retinoid did not show better results than radiotherapy alone (147).…”