Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas: An 8-year follow-up study of EPOCH

Purpose: Curative up-front regimens for non-Hodgkin's lymphomas contain dox orubicin, vincristine, and cyclophosphamide, whereas salvage regimens gener ally contain non-cross-resistant agents. We hypothesized that up-front agen ts may be highly effective for salvage and developed an infusional regimen based on in vitro evidence of increased efficacy. Patients and Methods: A prospective phase II study of etoposide, vincristin e, and doxorubicin over 96 hours with bolus cyclophosphamide and oral predn isone (EPOCH) was performed in 131 patients with relapsed or resistant lymp homa. Results: Seventy-nine percent of patients herd aggressive histologies, 46% were considered high risk by the International Prognostic Index, and 34% he rd resistant disease. Eighty-eight percent of patients held received at lea st four of the agents in EPOCH, and 94% had received doxorubicin. In 125 as sessable patients, 29 (24%) achieved complete responses and 60 (50%) achiev ed partial responses. Among 42 patients with resistant disease, 57% respond ed, and in 28 patients with relapsed aggressive de novo lymphomas, 89% resp onded with 54% complete responses. With a median follow-up of 76 months, th e overall and event-free survivals (EFS) were 17.5 and 7 months, respective ly. In 33 patients with sensitive aggressive disease who did not receive st em-cell transplantation, EFS was 19% at 36 months. Toxicity was primarily h ematologic, with an 18% incidence of febrile neutropenia. No clinically sig nificant cardiac toxicity was observed, despite no maximum cumulative doxor ubicin dose. Conclusion: EPOCH is highly effective in patients who had previously receiv ed most/all of the same drugs and produces durable remissions in curable su btypes. Salvage regimens need not contain non-crossresistant agents, and in fusional schedules may partially reverse drug resistance and reduce toxicit y. (C) 2000 by American Society of Clinical Oncology.