A cooperative study of epirubicin with cyclophosphamide, vincristine and prednisone (CEOP) in non-Hodgkin's lymphoma

Abstract

BACKGROUND. The purpose of our cooperative trial was to investigate whether epirubicin (EPI) at 90 mg/m2 in a CHOP-like combination (called CEOP) could increase complete response (CR) and survival rates in non-Hodgkin lymphoma (NHL) patients while maintaining a tolerable degree of toxicity. METHODS. Between September 1986 and July 1992, 218 patients from 12 Centers in Lombardy entered this study. The inclusion criteria were: a histological diagnosis of intermediate or diffuse large cell (DLC) NHL and no previous radio-chemotherapy. The patients in stages IA and IIA (both intermediate and DLC) received four CEOP courses followed by local/regional radiotherapy; those with intermediate NHL in stages IB, IIB, III A and B and IV A and B received six CEOP courses and, if they achieved CR, three further courses as consolidation. RESULTS. Among the 160 evaluable patients, CR was observed in 90% of the subjects with DLC-NHL (stages IA and IIA) and in 59% of those with intermediate-grade NHL (all clinical stages). If the clinical stages are considered separately, the CR rates were 92% for stages IA, IIA and 53% for stages IB, IIB, III A and B, IV A and B. Relapses occurred in 20% of the patients treated with four CEOP courses plus radiotherapy and in 31% of those who received nine CEOP courses because of the advanced stage of their disease. As of May 1994, the median follow-up was 42 months. If all of the patients are considered together, the 7-year overall survival (OS) probability was 64% and the 7-year disease-free survival (DFS) probability 67%. In comparison with stages III/IV, the patients in stages I-II had better DFS (7-year chance 77% vs 56%, p < 0.03). Hematological toxicity was acceptable, and a delay in the administration of CEOP chemotherapy was required in only three patients. No life-threatening infections were recorded. CONCLUSIONS. Our cooperative study of the use of the CEOP combination in NHL patients shows that response rates and the length of DFS are equal to the best results obtained with CHOP and more intensive programs, although further confirmation must be provided by means of a longer follow-up and a more careful analysis of prognostic factors according to the recently proposed international index. In our experience, an EPI dose of 90 mg/m2 has negligible toxicity (particularly on bone marrow), even in elderly patients. These findings are interesting since it is well known that myelotoxicity is the principal limiting factor for the majority of anthracycline-containing regimens used in the treatment of potentially curable NHL.