R-EPOCH Chemotherapy for Non-Hodgkin Lymphoma

An Overview of This Combination Chemo Treatment

R-EPOCH chemotherapy is a combination chemotherapy regimen used to treat certain malignancies, especially certain types of aggressive non-Hodgkin lymphoma (NHL).

The R-EPOCH regimen, also called EPOCH-R chemo, stands for the following drug agents:

  • R = Rituximab
  • E = Etoposide phosphate
  • P = Prednisone
  • O = Vincristine sulfate (Oncovin)
  • C = Cyclophosphamide
  • H = Doxorubicin hydrochloride (Hydroxydaunorubicin)
Doctor talking with patient at desk in office
Shannon Fagan / Getty Images


If you are already familiar with the acronym R-CHOP, a regimen commonly used for NHL, then you can think of the R-EPOCH chemo regimen as a “scrambled” version of R-CHOP with a few important differences.

R-EPOCH differs from R-CHOP not only in the addition of etoposide, but also in the scheduled delivery of the chemotherapy agents and their doses to the body.

R-EPOCH chemotherapy administration relies on infusions at variable concentrations over a longer period of time—four days. This is in contrast to traditional R-CHOP, whereby in each cycle, the CHOP is delivered all at once, in a so-called bolus-type administration.


DA-R-EPOCH, also referred to as DA-EPOCH-R, describes a regimen with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (and rituximab). In this variant of the regimen, doses of the chemotherapies are adjusted to try to maximize efficacy.

The DA-R-EPOCH regimen was developed at the National Cancer Institute (NCI) based on the hypothesis that optimization of drug selection, drug schedule, and drug exposure of the cancer cells would produce better outcomes than the CHOP regimen in people with aggressive NHL.

A 96-hour continuous infusion regimen was developed, whereby DA-R-EPOCH is administered every 21 days. Dose adjustments to doxorubicin, etoposide, and cyclophosphamide are made based on the lowest count (absolute neutrophil count nadir) in the previous cycle.

Research on R-EPOCH for DLBCL Subsets

Lymphomas are generally grouped into two main categories: Hodgkin lymphoma (HL) and NHL. Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell NHL, occurring in 30% to 35% of cases and affecting people of all ages.

The World Health Organization (WHO) classifies DLBCL into four major categories. The largest category—DLBCL not otherwise specified—can be further subdivided into three subtypes based on the cell of origin. They include:

  • Germinal center B-cell–like (GCB)
  • Activated B-cell (ABC)
  • Primary mediastinal B-cell lymphoma (PMBL)

In other words, when looking at the molecular level, DLBCL is a diverse group of lymphomas and different types of DLBCL may have different prognoses with treatment. In addition, a related type of aggressive lymphoma is called "double hit" lymphoma. It has specific genetic abnormalities that may affect outcomes.

At one time, there was hope that results with dose-adjusted R-EPOCH would be superior to R-CHOP generally for people with DLBCL. While this still may be true in selected subsets, it seems not to be the case generally, at least based on existing evidence.

A study of 491 participants compared the efficacy of R-CHOP and DA-R-EPOCH regimens in treating DLBCL people, specifically in GCB and ABC subtypes. Participants were assigned to receive either R-CHOP or DA-EPOCH-R.

At a median follow-up of about five years, survival outcomes were similar between the groups. DA-R-EPOCH showed increased toxicity, but this was expected based on the higher dose intensity. Still, researchers were quick to point out that more analyses are required to determine the effect of various regimens on specific subsets of people with DLBCL.

The use of genetic and other information about diffuse large B-cell lymphoma (DLBCL) can potentially alter treatment, but this is currently somewhat of an unsettled area and the topic of ongoing research.

DLBCL With High Ki-67 Expression

Ki-67 is a marker that has been used in various cancers as a proliferation index—that is, a marker of cell growth in regard to cell division. Tumors with high proliferation are expected to have high expression of Ki-67.

The EPOCH regimen was developed in part based on the concept that the extension of drug exposure may yield better antitumor efficacy than a bolus regimen, such as CHOP.

In a previous study, it was determined that DLBCL people with high Ki-67 expression received limited survival benefits from R-CHOP therapy. Another study was launched to find if R-EPOCH is superior to R-CHOP in untreated DLBCL people with high Ki-67 expression.

The R-EPOCH chemotherapy regimen was given as first-line treatment in DLBCL people with high Ki-67 expression. It was compared to the treatment efficacy of R-EPOCH and R-CHOP therapy in this Ki-67 subgroup.

Results suggested that people treated with the R-EPOCH regimen exhibited better survival than those administered the R-CHOP regimen, but more study is needed to confirm the findings and to identify possible prognostic biomarkers for use with R-EPOCH therapy.

Double Hit Lymphoma

Double hit lymphomas, or DHLs, account for 5% to 10% of DLBCL cases, and the majority can be profiled as the germinal center type and express the genes BCL-2 (BCL-2+/MYC+). A small subset of DHLs express BCL-6 (BCL-6+/MYC+) or express both BCL-2 and BCL-6 and are called triple-hit lymphomas (BCL-2+/BCL-6+/MYC+).

People with DHLs often have poor prognostic features, high international prognostic index (IPI) scores, and involvement of the bone marrow or the central nervous system. The best regimen for DHLs is not known; however, people who received R-CHOP–like regimens have a poor prognosis, with a median overall survival of fewer than 12 months.

In a retrospective review, the overall progression-free survival improved with more intensive regimens, including DA-EPOCH-R, compared with R-CHOP. The DA-EPOCH-R regimen resulted in significantly higher rates of complete remission than the other intensive regimens.

Primary Mediastinal Lymphoma (PMBL)

Primary mediastinal lymphoma (PMBL) is another subtype of DLBCL that represents 10% of DLBCL cases. It is clinically and biologically related to nodular sclerosing Hodgkin lymphoma, which also arises from thymic B-cells.

PMBL is aggressive and develops into a mediastinal mass. Most people have mutations in the BCL-6 gene. Standard immunochemotherapy is not effective, and most people require mediastinal radiation, which may lead to late adverse effects.

In a retrospective analysis, the failure rate for the R-CHOP chemotherapy protocol was 21%, suggesting the need for treatment alternatives.

Primary mediastinal lymphoma (PMBL) is a relatively rare lymphoma with not a lot of clinical study data. However, data looking back at past cases (retrospective studies) suggest that more intensive treatments appear to be more effective than R-CHOP.

DA-EPOCH-R uses infused doses of the drugs etoposide, doxorubicin, and cyclophosphamide that are adjusted for optimal effect. Results of one study followed 51 people diagnosed with primary mediastinal B-cell lymphoma, for a period of up to 14 years.

It found that all but two people achieved a complete remission with DA-EPOCH-R therapy. None of the people with a complete remission developed a recurrent lymphoma in later monitoring. The two others received radiation and had also not had their tumors recur. There was no evidence of other diseases developing later on or cardiac toxic effects.

A broad study of adults with PMBL compared overall survival in people treated with these regimens. They included 132 from 11 treatment centers, 56 of them receiving R-CHOP and 76 receiving DA-R-EPOCH. Complete remission rates were higher with DA-R-EPOCH (84% vs. 70%) but these people were more likely to experience treatment-related toxicities.

At two years, 89% of R-CHOP people and 91% of DA-R-EPOCH people remained alive.

R-EPOCH for Burkitt Lymphoma

Burkitt lymphoma is more common in equatorial Africa than in Western countries. Burkitt is a disease that occurs frequently in immune-suppressed people living with AIDS.

Cure rates for Burkitt lymphoma in Western countries approach 90% in children, but only 30% to 50% of African children are cured due to an inability to safely administer high-dose treatment.

One study trial involved two variants of EPOCH-R, with longer exposures to lower concentrations of drugs instead of briefer exposures to higher concentrations of drugs. Thirty people with previously untreated Burkitt lymphoma were included, and given one of the two EPOCH-R variants, depending on their HIV status.

Nineteen HIV-negative people received DA-EPOCH-R, while 11 HIV-positive people received SC-EPOCH-RR, a short-course variant of EPOCH-R that includes two doses of rituximab per treatment cycle and has a lower treatment intensity than DA-EPOCH-R.

Adjustment of dose levels is done to try to provide the optimum amount of drug based on a person’s tolerance of chemotherapy. The main toxicities seen in the trial were fever and neutropenia (low white blood cell counts); no treatment-related deaths occurred.

With median follow-up times of 86 and 73 months, the overall survival rates were 100% for the DA-EPOCH-R group and 90% for those treated with SC-EPOCH-RR.

Based on these results, more studies were started to confirm the efficacy of EPOCH-R therapy in both adults and children diagnosed with Burkitt lymphoma.

A Word From Verywell 

The R-EPOCH chemotherapy regimen and its variants, including DA-R-EPOCH, are tailored to treat people with specific types and subtypes of aggressive non-Hodgkin lymphoma. They show promise in treating certain people with DLBCL and other malignancies. If you fall into these subsets, discuss the option with your healthcare provider.

Frequently Asked Questions

  • How much does dose-adjusted EPOCH-R cost?

    When treating high-risk DLBCL cancers in the United States, researchers found the cost of DA-R-EPOCH to average $106,940. The cost for R-CHOP in the same analysis was $58,509. Costs vary widely based on the type of EPOCH-R chemo, your location, and country.

  • What are the side effects of R-EPOCH chemotherapy?

    The doxorubicin used in R-EPOCH and R-CHOP treatments has toxic effects on the heart. Prednisone used in the DA-R-EPOCH and R-CHOP treatments can cause high blood sugar, even in people without diabetes. Other common side effects of chemo include fatigue and nausea.

  • How long does R-CHOP chemo stay in your system?

    R-CHOP chemotherapy drugs stay in your system for up to a few days, but keep in mind that those doses are given in cycles of more than one treatment. People with DLBCL and PMBL types of NHL typically get chemo every three weeks, for up to six cycles, depending on the stage.

13 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  8. Shah NN, Szabo A, Huntington SF. R-CHOP versus dose-adjusted R-EPOCH in frontline management of primary mediastinal B-cell lymphoma: a multi-centre analysisBritish Journal of Haematology. 2017;180(4):534-544. doi:10.1111/bjh.15051

  9. Curry MA, Liewer S. Making an Informed Treatment Choice for Aggressive Non-Hodgkin Lymphoma: The R-CHOP Regimen versus EPOCH-RJ Hematol Oncol Pharm. 2016;6(4):145-152. December 2016.

  10. Dholaria B, Vanegas YAM, Diehl N, Spaulding AC, Visscher S, Tun HW, et al. Cost Analysis of R-CHOP Versus Dose-Adjusted R-EPOCH in Treatment of Diffuse Large B-Cell Lymphoma with High-Risk Features. Clin Hematol Int. 2020 Apr 23;2(3):117-124. doi: 10.2991/chi.d.200410.001

  11. Cherukuri SV, Sureen A, Infante T, Rajendran N, Padilla O, Gaur S. Treatment of Primary Mediastinal B-Cell Lymphoma With R-CEOP (Rituximab, Cyclophosphamide, Etoposide, Vincristine, and Prednisone). Cureus. 2021 Jul 2;13(7):e16128. doi:10.7759/cureus.16128

  12. Lamar ZS, Dothard A, Kennedy L, Isom S, Robinson M, Vaidya R, et al. Hyperglycemia during first-line R-CHOP or dose adjusted R-EPOCH chemotherapy for non-Hodgkin lymphoma is prevalent and associated with chemotherapy alteration - a retrospective study. Leuk Lymphoma. 2018 Aug;59(8):1871-1877. doi:10.1080/10428194.2017

  13. American Cancer Society. Treating B-Cell Non-Hodgkin Lymphoma.

Additional Reading
  • Curry MA, Liewer S. Making an informed treatment choice for aggressive non-Hodgkin lymphoma: the R-CHOP regimen versus EPOCH-R. J Hematol Oncol Pharm. 2016;6(4):145-152.

By Tom Iarocci, MD
Tom Iarocci, MD, is a medical writer with clinical and research experience in hematology and oncology.