JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH 10:669–674 (2001) Mary Ann Liebert, Inc. Chemotherapy Plus Interferon-a2b Versus Chemotherapy in the Treatment of Follicular Lymphoma NATIVIDAD NERI, 1 AGUSTIN AVILÉS, 2 SERGIO CLETO, 1 NOE DÍAZ, 1 ALEJANDRA TALAVERA, 1 EDNA L. GARCÍA, 1 and JOSÉ C. DÍAZ-MAQUEO 1 ABSTRACT The best treatment of follicular lymphoma remains to be determined because the long natural his- tory of follicular lymphoma requires mature data for accurate analysis. Although the goal of pri- mary treatment remains durable remission, the sequential application of effective treatments may also result in a prolongation of median survival time. The use of interferon (IFN) with doxorubicin- based chemotherapy has demonstrated an increase of event-free survival but not in overall survival; however, its acute and late cardiac toxicity limits its use. For this reason, we began a controlled clin- ical trial to assess the efficacy and toxicity of chemotherapy: COPP (cyclophosphamide, vincristine, prednisone, and procarbazine) 1 IFN alternating every month for six cycles compared to six cycles of chemotherapy. In an intent-to treat analysis, 55 patients were enrolled (median age 61 years). Most cases (91%) with advanced disease were randomly assigned to chemotherapy 1 IFN (28 cases) or chemotherapy (27 cases). Complete remission was observed in 16 patients: 59% (95% CI, 53–70%) in the chemotherapy arm compared to 20 patients 71% (95% CI, 58–79%) in the chemotherapy 1 IFN arm; total responses were 74% and 86%, respectively. At a median follow-up of 60 months, event-free survival was 100% for patients treated with chemotherapy 1 IFN, which was statistically different from patients treated with chemotherapy 70%. At 7 years, median survival has not yet been reached; 72% of patients chemotherapy 1 IFN remain alive without disease (95% CI, 59–81%), which is not statistically different from 72% (95%CI, 50–73%) in the chemotherapy arm. Non- hematological toxicity was most frequent and severe in the chemotherapy arm; hematological tox- icity was similar in both groups. Thus, it appears that chemotherapy 1 IFN, as described herein, improves event-free survival but the overall survival rates remain unchanged. The use of COPP ap- pears to be better that anthracycline-based chemotherapy because it avoids the presence of acute and late cardiac toxicity. 669 INTRODUCTION F OLLICULAR LYMPHOMAS (FL) account for 30–40% of all non-Hodgkin’s lymphomas, and their incidence is steadily increasing in North America and Europe (1). Most patients with FL have disseminated disease with bulky nodal and/or extranodal tumors. Nevertheless, che- motherapy induces tumor regression but does not seem to improve survival significantly and the median dura- tion of the first complete remission is often short (rang- ing from 12 to 36 months) (2). Although FL remains re- sponsive following relapse, the duration of subsequent remissions decreases progressively. Moreover in 15–70% of patients, FL eventually undergoes histologic conver- 1 Department of Hematology, Oncology Hospital, National Medical Center, IMSS, Mexico, D.F. Mexico. 2 Senior Researcher, Research Unit in Oncology Disease. Oncology Hospital, National Medical Center, IMSS, Mexico D.F.