Dose Adjusted EPOCH Chemotherapy Plus Rituximab Combination (DA-R-EPOCH), an Effective Upfront Therapy for Patients with Poor-Risk Aggressive B-Cell Lymphomas. Results of a Pilot Study in a Single Center.

Poor risk aggressive non-Hodgkin’s lymphomas have a short EFS and OS when treated with conventional chemotherapy schedules. High dose therapy followed by stem cell rescue has been attempted with disparate results. Based on Wilson WH et al. schedule (

Methods. From August 2002 to May 2005, 28 untreated patients (pts) were enrolled in the study. Basically the regimen consisted on 6 cycles every 21 days of Rituximab (day 1) followed by a 96 hours infusion of etoposide, vincristine and doxorubicine and bolus cyclophosphamide on day 5 plus prednisone for 5 days. The doxorubicine, etoposide and cyclophosphamide doses were adjusted according to the hematological toxicity as reported by Wilson WH et al (Wilson WH, Gutierrez M, O’Connor P et al. 2002; 29 (Suppl. 2):41–7). Response rate and survivals were calculated in intention to treat. Pts not reaching a PR ≥ 70% after 3 cycles or a CR/CRu after completion of therapy were assigned as failure in the time to treatment failure (TTF) calculation.

Results. Patients characteristics: median age 62,5 years (range:26–72); male/female: 11/17; DLBCL 21 (75%) and G3bFL 7 (25%); 19 (68%) had IV clinical stage; 13 (46%) B symptoms; PS (ECOG) > 2 in 12 pts (42%); 21 pts (75%) had extranodal and 10 (36%) bone marrow involvement; 32% had serum albumin < 3 g/dL; Hb < 100 g/L in 13 (46%); 46% had high b2microglobulin levels, and 100% elevated LDH. High age-adjusted IPI score in 15 pts (54%). Dose adjustment: Dose escalation could be done in most patients (18 out of 21 receiving all 6 cycles). There were an inverse correlation between the mean dose of doxurubicin given and age (r=−0.555; P2=0.009) and IPI (r=−0.507; P2=0.019). Response and survival: 17 out of 23 pts evaluated for response (74%) achieved a CR/CRu. There were 2 early deaths. At a median follow up of 14 months (range: 2–35) the estimated 2-year TTF and OS were 58% and 73% respectively. Toxicity: After 143 cycles administered grade 3–4 mucositis was observed in 9 courses (6%), grade 3–4 nueropathy in 1 (<1%) and neutropenic fever in 20 (14%).

Conclusion. DA-R-EPOCH is a feasible approach and as effective as other more intensive chemotherapy schedules as upfront therapy in patients with intermediate-high or high risk IPI score aggressive large B-cell lymphomas (DLBCL and G3bFL) with acceptable toxicity. Updated data will be presented at the meeting.