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

Mycosis fungoides is a T-cell lymphoma that arises in the skin and progresses at highly variable rates. Nonrandomized 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. (N Engl J Med 1989; 321:1784–90.) MYCOSIS FUNGOIDES is a generally indolent cutaneous T-cell lymphoma characterized by a neoplastic proliferation of mature helper T cells. 1 2 3 4 Clinically distinct presentations of mycosis fungoides include limited or widespread cutaneous plaques, cutaneous tumors, and the Sézary syndrome (erythroderma associated with abnormal circulating cells). Although mycosis fungoides is first manifested in the skin, occult systemic involvement can be found at presentation and is common at later stages, when there is invasion of the lymph nodes, blood, and viscera. 5 , 6 Several studies have demonstrated the ability of localized treatments, such as topical chemotherapeutic agents, 7 , 8 psoralen plus ultraviolet-A exposure, 9 10 11 and electron-beam radiation therapy, 12 13 14 to . . .