Dose‐adjusted EPOCH plus rituximab is an effective regimen in patients with poor‐prognostic untreated diffuse large B‐cell lymphoma: results from a prospective observational study

Abstract

Summary This study was designed to assess the efficacy and safety of an infusional DA‐EPOCH (dose‐adjusted etoposide/vincristine/doxorubicin/bolus cyclophosphamide/prednisone) and rituximab (DA‐EPOCH‐R) regimen for patients with poor prognosis diffuse large B‐cell lymphoma (DLBCL). Thirty‐three patients, aged 21–76 years, with an age‐adjusted International Prognostic Index (IPI) of 2 or 3, were enrolled, and 31/33 patients were evaluable for response. Consolidative radiation therapy was given to eight patients with bulky (≥10 cm) disease at presentation. Overall, 26 patients (83·8%) achieved a complete remission (CR), four patients (12·9%) achieved a partial remission, and one patient (3·2%) died during induction. Two patients relapsed (7·6%) within 15 months. Grade 3–4 neutropenia developed in 52% of cycles and neutropenic fever in 14% of cycles (51% of patients). The estimates for event‐free survival (EFS) and overall survival at 2 years were 68% and 75% respectively. The only factor related to poor EFS was the presence of three age‐adjusted IPI‐risk factors. We conclude that DA‐EPOCH‐R has clinically significant activity with a favourable toxicity profile for poor‐prognostic DLBCL patients. The administration of DA‐EPOCH‐R as an outpatient regimen by using a single portable infusion pump may be a feasible alternative to improve the compliance and to reduce the total cost of this very effective regimen.

Activity and safety of dose‐adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab in very elderly patients with poor‐prognostic untreated diffuse large B‐cell non‐Hodgkin lymphoma

“…Etoposide was omitted and, in view of an outpatient care program, cyclophosphamide was administered on Day 1 together with rituximab to deliver both the noncontinuously infused drugs on the same day of each cycle. Our data confirm efficacy and safety of dynamic dose adjustment of infusional doxorubicin in DLBCL patients, providing additional support for results already published with DA-EPOCH-R, [15][16][17][18] albeit not specifically restricted to elderly population (Table 6). …”

“…As expected, the most frequent grade 3 to 4 AEs were neutropenia and febrile neutropenia, which occurred in 48% and 13% of patients, respectively. However, the observed rates of AEs with DA-POCH-R did not differ from those reported in other dose-adjusted regimens [14][15][16][17] and were substantially lower than AE rates observed in a series of doxorubicin-free protocols [31][32][33][34][35][36][37][38][39][40]42,44 specifically tailored for elderly patients with DLBCL (Table 6).…”

“…Twenty-one percent of these patients experienced cardiac adverse events, graded as 3 to 4 in 4% of the cases. Our treatment schema was derived from the DA-EPOCH-R regimen, 16,17 with modest modifications. Etoposide was omitted and, in view of an outpatient care program, cyclophosphamide was administered on Day 1 together with rituximab to deliver both the noncontinuously infused drugs on the same day of each cycle.…”

“…13,14 Dynamic dose adjustment of the EPOCH regimen (DA-EPOCH) has resulted in dose escalations, limited hematopoietic toxicity, and no cardiac complications or treatment-related deaths, even in patients with acquired immunodeficiency syndrome (AIDS) -related lymphoma. [15][16][17][18] The addition of rituximab (monoclonal anti-CD20 antibody) to the conventional CHOP regimen (R-CHOP) has been reported to increase the likelihood of response and long-term event-free survival, with no overlapping toxicity, in elderly patients with poor-prognosis DLBCL. 19 The objective of this study was to assess efficacy and safety, with special attention to hematological and cardiac toxicity, of the combination of rituximab and dose-adjusted infusional CHOP chemotherapy (DA-POCH-R) for patients with poor-prognostic untreated DLBCL aged >70 years and over.…”

“…19 The objective of this study was to assess efficacy and safety, with special attention to hematological and cardiac toxicity, of the combination of rituximab and dose-adjusted infusional CHOP chemotherapy (DA-POCH-R) for patients with poor-prognostic untreated DLBCL aged >70 years and over. Unlike DA-EPOCH plus rituximab regimen (DA-EPOCH-R), 16,17 infusional etoposide was not included in the study treatment schema to maintain the same drug combination of standard R-CHOP therapy.…”