# Alliance/CALGB 50303

Source: https://onco.cc/trials/calgb-50303/  
OnCo record `calgb-50303` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An intensive infusion chemotherapy schedule, widely believed to be better for aggressive lymphoma, was compared head to head with the standard and was not better, only harder to tolerate.

## Summary

Dose-adjusted EPOCH-R gives cyclophosphamide, doxorubicin and etoposide as a 96-hour infusion with the dose raised or lowered by the neutrophil count in the previous cycle. Single-arm series had reported excellent results, and many centres had adopted it for higher-risk diffuse large B-cell lymphoma on that basis. CALGB 50303 randomised it against R-CHOP in untreated disease between 2005 and 2013.

At a median follow-up of five years there was no difference. Progression-free survival gave a hazard ratio of 0.93 (95 per cent confidence interval 0.68 to 1.27, p = 0.65), with two-year rates of 78.9 per cent for dose-adjusted EPOCH-R and 75.5 per cent for R-CHOP; overall survival gave a hazard ratio of 1.09 (0.75 to 1.59, p = 0.64). Grade 3 and 4 adverse events were more common with the infusional regimen, 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.

The authors' own reading is the honest one: the R-CHOP results were better than historical controls, which suggests the trial selected a favourable population and that the answer may not generalise to the highest-risk subgroups. Dose-adjusted EPOCH-R remains standard in primary mediastinal B-cell lymphoma and in HIV-associated lymphoma, where it was tested separately, and is still used in high-grade B-cell lymphoma with MYC and BCL2 rearrangements on non-randomised evidence.

## Fields

- Kind: Trial
- Status: negative
- Last checked: 2026-10-01
- Also known as: CALGB 50303; Alliance 50303; DA-EPOCH-R versus R-CHOP
- Tags: lymphoma-evidence
- Registry id: NCT00118209
- Phase: 3
- Setting: Untreated diffuse large B-cell lymphoma: six cycles of dose-adjusted EPOCH-R against six cycles of R-CHOP
- Sponsor: Alliance for Clinical Trials in Oncology
- Enrolled: 491
- Result: No difference in progression-free survival (hazard ratio 0.93) or overall survival (1.09) against R-CHOP, with substantially more febrile neutropenia, mucositis and neuropathy.
- Outcomes: Progression-free survival: Dose-adjusted EPOCH-R vs R-CHOP, HR 0.93; Overall survival: Dose-adjusted EPOCH-R vs R-CHOP, HR 1.09; Febrile neutropenia: Dose-adjusted EPOCH-R 35% vs R-CHOP 17.7%
- Replication: The only randomised comparison of the two regimens in unselected diffuse large B-cell lymphoma.

## Sources

- ClinicalTrials.gov NCT00118209: https://clinicaltrials.gov/study/NCT00118209
- Journal of Clinical Oncology 2019: https://doi.org/10.1200/JCO.18.01994

## Connected records

- 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/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-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: [International Prognostic Index (IPI)](https://onco.cc/terms/ipi-score/), [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/)
- bottlenecks: [Failures are hidden](https://onco.cc/bottlenecks/b-negative-results/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- key papers: [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](https://onco.cc/key-papers/paper-calgb-50303-da-epoch-r-vs-r-chop-jco-2019/)
- 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/)

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