# Dose-adjusted EPOCH-R compared with R-CHOP as frontline therapy for diffuse large B-cell lymphoma: clinical outcomes of the phase III intergroup trial Alliance/CALGB 50303

Source: https://onco.cc/key-papers/paper-calgb-50303-da-epoch-r-vs-r-chop-jco-2019/  
OnCo record `paper-calgb-50303-da-epoch-r-vs-r-chop-jco-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An intensive infusional chemotherapy regimen that many centres had adopted on single-arm evidence was no better than the standard when finally compared head to head, and was harder to tolerate.

## Summary

An intergroup phase 3 trial comparing six cycles of dose-adjusted EPOCH-R with six cycles of R-CHOP as frontline therapy for diffuse large B-cell lymphoma. 524 patients were registered between 2005 and 2013 and 491 were eligible for the final analysis; 74 per cent had stage III or IV disease.

At a median follow-up of five years, progression-free survival did not differ (hazard ratio 0.93, 95 per cent confidence interval 0.68 to 1.27, p = 0.65) with two-year rates of 78.9 and 75.5 per cent, and neither did overall survival (hazard ratio 1.09, 0.75 to 1.59, p = 0.64) with two-year rates of 86.5 and 85.7 per cent. Grade 3 and 4 adverse events were more common with dose-adjusted EPOCH-R, including febrile neutropenia in 35.0 against 17.7 per cent, mucositis in 8.4 against 2.1 per cent and neuropathy in 18.6 against 3.3 per cent. Five treatment-related deaths occurred in each arm.

## Fields

- Kind: Key paper
- Last checked: 2026-10-01
- Also known as: CALGB 50303; Bartlett 2019
- Tags: lymphoma-evidence
- Journal: Journal of Clinical Oncology
- Year: 2019
- DOI: 10.1200/JCO.18.01994
- Authors: Bartlett NL, Wilson WH, Jung SH, et al.
- Findings: Progression-free survival did not differ between dose-adjusted EPOCH-R and R-CHOP (hazard ratio 0.93, 95 per cent confidence interval 0.68 to 1.27, p = 0.65).; Two-year progression-free survival was 78.9 per cent for dose-adjusted EPOCH-R and 75.5 per cent for R-CHOP.; Overall survival did not differ (hazard ratio 1.09, 0.75 to 1.59, p = 0.64).; Febrile neutropenia occurred in 35.0 against 17.7 per cent, mucositis in 8.4 against 2.1 per cent and neuropathy in 18.6 against 3.3 per cent.; Five treatment-related deaths (2.1 per cent) occurred in each arm.
- What it means: R-CHOP remains the standard first-line regimen for diffuse large B-cell lymphoma. The trial is also the clearest lesson in the disease about adopting a regimen on single-arm data: dose-adjusted EPOCH-R had been used widely for a decade before this comparison existed.
- Caveats: The authors note that R-CHOP results were better than historical controls, which suggests patient selection and limits generalisability to specific high-risk subgroups.; Not powered for subgroups such as double-hit lymphoma, where dose-adjusted EPOCH-R is still used on non-randomised evidence.; Primary mediastinal B-cell lymphoma and HIV-associated lymphoma, where dose-adjusted EPOCH-R has its strongest evidence, were studied separately.

## Sources

- Journal of Clinical Oncology 2019: https://doi.org/10.1200/JCO.18.01994
- PubMed: https://pubmed.ncbi.nlm.nih.gov/30939090/
- Europe PMC: https://europepmc.org/article/MED/30939090

## Connected records

- key papers: [Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma](https://onco.cc/key-papers/paper-dunleavy-da-epoch-r-pmbcl-nejm-2013/)
- roadmaps: [Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting](https://onco.cc/roadmaps/lymphoma-roadmap/)
- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- fronts: [Chemotherapy](https://onco.cc/fronts/chemotherapy/)
- drugs: [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Etoposide](https://onco.cc/drugs/etoposide/), [Prednisone](https://onco.cc/drugs/prednisone/), [Rituximab](https://onco.cc/drugs/rituximab/), [Vincristine](https://onco.cc/drugs/vincristine/)
- institutions: [National Cancer Institute (NIH)](https://onco.cc/institutions/nci/)
- terms: [Double-hit / high-grade B-cell lymphoma](https://onco.cc/terms/double-hit-lymphoma/), [R-CHOP (lymphoma chemoimmunotherapy)](https://onco.cc/terms/r-chop/), [The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest](https://onco.cc/terms/lymphoma-tx-regimen-alphabet/)
- trials: [Alliance/CALGB 50303](https://onco.cc/trials/calgb-50303/)
- bottlenecks: [Failures are hidden](https://onco.cc/bottlenecks/b-negative-results/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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