PURPOSE: Curative up-front regimens for non-Hodgkin's lymphomas contain doxorubicin, vincristine, and cyclophosphamide, whereas salvage regimens generally contain non-cross-resistant agents. We hypothesized that up-front agents 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, vincristine, and doxorubicin over 96 hours with bolus cyclophosphamide and oral prednisone (EPOCH) was performed in 131 patients with relapsed or resistant lymphoma. RESULTS: Seventy-nine percent of patients had aggressive histologies, 46% were considered high risk by the International Prognostic Index, and 34% had resistant disease. Eighty-eight percent of patients had received at least four of the agents in EPOCH, and 94% had received doxorubicin. In 125 assessable patients, 29 (24%) achieved complete responses and 60 (50%) achieved partial responses. Among 42 patients with resistant disease, 57% responded, and in 28 patients with relapsed aggressive de novo lymphomas, 89% responded with 54% complete responses. With a median follow-up of 76 months, the overall and event-free survivals (EFS) were 17.5 and 7 months, respectively. In 33 patients with sensitive aggressive disease who did not receive stem-cell transplantation, EFS was 19% at 36 months. Toxicity was primarily hematologic, with an 18% incidence of febrile neutropenia. No clinically significant cardiac toxicity was observed, despite no maximum cumulative doxorubicin dose. CONCLUSION: EPOCH is highly effective in patients who had previously received most/all of the same drugs and produces durable remissions in curable subtypes. Salvage regimens need not contain non-cross-resistant agents, and infusional schedules may partially reverse drug resistance and reduce toxicity.
PURPOSE: Curative up-front regimens for non-Hodgkin's lymphomas contain doxorubicin, vincristine, and cyclophosphamide, whereas salvage regimens generally contain non-cross-resistant agents. We hypothesized that up-front agents 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, vincristine, and doxorubicin over 96 hours with bolus cyclophosphamide and oral prednisone (EPOCH) was performed in 131 patients with relapsed or resistant lymphoma. RESULTS: Seventy-nine percent of patients had aggressive histologies, 46% were considered high risk by the International Prognostic Index, and 34% had resistant disease. Eighty-eight percent of patients had received at least four of the agents in EPOCH, and 94% had received doxorubicin. In 125 assessable patients, 29 (24%) achieved complete responses and 60 (50%) achieved partial responses. Among 42 patients with resistant disease, 57% responded, and in 28 patients with relapsed aggressive de novo lymphomas, 89% responded with 54% complete responses. With a median follow-up of 76 months, the overall and event-free survivals (EFS) were 17.5 and 7 months, respectively. In 33 patients with sensitive aggressive disease who did not receive stem-cell transplantation, EFS was 19% at 36 months. Toxicity was primarily hematologic, with an 18% incidence of febrile neutropenia. No clinically significant cardiac toxicity was observed, despite no maximum cumulative doxorubicin dose. CONCLUSION: EPOCH is highly effective in patients who had previously received most/all of the same drugs and produces durable remissions in curable subtypes. Salvage regimens need not contain non-cross-resistant agents, and infusional schedules may partially reverse drug resistance and reduce toxicity.
Authors: Wyndham H Wilson; Sin-Ho Jung; Pierluigi Porcu; David Hurd; Jeffrey Johnson; S Eric Martin; Myron Czuczman; Raymond Lai; Jonathan Said; Amy Chadburn; Dan Jones; Kieron Dunleavy; George Canellos; Andrew D Zelenetz; Bruce D Cheson; Eric D Hsi Journal: Haematologica Date: 2011-12-01 Impact factor: 9.941
Authors: Joseph A Sparano; Abdissa Negassa; Erick Lansigan; Robin Locke; Chamath R De Silva; Peter H Wiernik Journal: Med Oncol Date: 2005 Impact factor: 3.064
Authors: Keni Gu; Dennis D Weisenburger; Kai Fu; Wing C Chan; Timothy C Greiner; Patricia Aoun; Lynette M Smith; Martin Bast; Zhongfen Liu; R Gregory Bociek; Philip J Bierman; James O Armitage; Julie M Vose Journal: Hematol Oncol Date: 2011-10-18 Impact factor: 5.271
Authors: Nancy L Bartlett; Wyndham H Wilson; Sin-Ho Jung; Eric D Hsi; Matthew J Maurer; Levi D Pederson; Mei-Yin C Polley; Brandelyn N Pitcher; Bruce D Cheson; Brad S Kahl; Jonathan W Friedberg; Louis M Staudt; Nina D Wagner-Johnston; Kristie A Blum; Jeremy S Abramson; Nishitha M Reddy; Jane N Winter; Julie E Chang; Ajay K Gopal; Amy Chadburn; Susan Mathew; Richard I Fisher; Kristy L Richards; Heiko Schöder; Andrew D Zelenetz; John P Leonard Journal: J Clin Oncol Date: 2019-04-02 Impact factor: 44.544