EPOCH and R-EPOCH are intensive chemotherapy regimens primarily used to treat aggressive forms of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, mantle cell lymphoma, and Burkitt lymphoma. EPOCH includes five drugs (etoposide, prednisone, vincristine, cyclophosphamide, and hydroxydaunorubicin), and is often combined with rituximab (R-EPOCH) for CD20-positive lymphomas. Most medications are given intravenously, and are administered over 4–5 days.

What Does EPOCH Stand For?

The acronym EPOCH stands for the following drugs:

• E – Etoposide: a topoisomerase II inhibitor that blocks cell division.
• P – Prednisone: a steroid that kills cancer cells.
• O – Oncovin (vincristine): a vinca alkaloid that prevents cell division.
• C – Cyclophosphamide: an alkylating agent that damages DNA.
• H – Hydroxydaunorubicin (doxorubicin): an anthracycline that damages DNA and prevents cell division.

When rituximab (R)—a monoclonal antibody targeting CD20 on B-cells—is added, the regimen is called R-EPOCH or EPOCH-R. Rituximab enhances the destruction of both normal and malignant B-cells by the immune system.

How Is EPOCH/R-EPOCH Administered?

EPOCH/R-EPOCH is typically given over 4–5 days during each cycle via continuous IV infusion, with prednisone taken orally. The IV medications may be given through a central line, PICC line, or portacath. Cycles are generally 21 days long, and they are repeated for multiple cycles (often 6). Treatment may require hospitalization or home infusion depending on the center.

Medications in an EPOCH/R-EPOCH chemotherapy cycle are usually given as follows:

• Rituximab (if getting R-EPOCH): Given IV on Day 1.
• Prednisone: Given orally on Days 1-5.
• Doxorubicin: Given IV on Days 1-4.
• Vincristine: Given IV on Days 1-4.
• Etoposide: Given IV on Days 1-4.
• Cyclophosphamide: Given IV on Day 5.

Other medications may be given as pretreatment and for management of side effects, such as antibiotics and growth factors.

Dose Adjustment (DA-EPOCH)

A key feature of EPOCH is its dose-adjusted approach (DA-EPOCH). Doses of etoposide, doxorubicin, and cyclophosphamide may be increased or decreased in subsequent cycles based on the patient's blood counts and ability to tolerate side effects, particularly neutropenia and thrombocytopenia. This personalized adjustment aims to maximize efficacy while minimizing toxicity.

When Is EPOCH Used?

EPOCH (and its variant with rituximab, R-EPOCH) is used as a chemotherapy regimen primarily for certain aggressive lymphomas and related malignancies. Its use is guided by the type of lymphoma, risk factors, and patient-specific considerations.

• Aggressive B-cell Non-Hodgkin Lymphomas: EPOCH is considered a gold standard for treating various B-cell non-Hodgkin lymphoma subtypes, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, primary mediastinal B-cell lymphoma, high-grade B-cell lymphomas, including those with MYC, BCL2, and/or BCL6 rearrangements ("double-hit" or "triple-hit" lymphomas).
• HIV-associated Lymphomas: EPOCH (often with rituximab) is used in patients with HIV-associated DLBCL and high-grade lymphomas.
• Peripheral T-cell Lymphoma: Dose-adjusted EPOCH has also been explored as a first-line treatment for peripheral T-cell lymphoma, showing promising response rates and outcomes.

EPOCH chemotherapy is preferred when more intensive regimens are needed due to high-risk disease features.

How Effective Is EPOCH?

EPOCH (and R-EPOCH) chemotherapy regimens have demonstrated high effectiveness, particularly in aggressive and high-risk lymphomas, including cases resistant to standard treatments.

Relapsed or Resistant Lymphoma

• In a phase II study of patients with aggressive lymphomas who had relapsed or were resistant to prior regimens (often containing the same drugs as EPOCH), 27% achieved a complete remission (CR) and 60% achieved a partial remission (PR).
• Among patients who had no response to prior chemotherapy, 71% responded to EPOCH, though only one achieved a complete response.
• Those who relapsed after an initial CR had a 100% response rate, with 76% achieving another CR. At one year, 28% of patients remained event-free.

First-Line and High-Risk Lymphoma

• EPOCH (especially with rituximab as R-EPOCH) is considered an effective first-line treatment for B-cell non-Hodgkin lymphoma, including Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL).
• A phase 3 study of patients with diffuse large B-cell lymphoma found that patients treated with R-DA-EPOCH and R-CHOP as frontline therapy had similar outcomes in terms of progression-free survival (PFS) and overall survival (OS). 2-year PFS was 75-79%, and 2-year OS was 86-87%.
• In rare forms of aggressive B-cell lymphoma, dose-adjusted R-EPOCH achieved an overall response rate of 87%, with 74% achieving complete response. Four-year event-free and OS rates were 71% and 77%, respectively.
• A retrospective study of patients with aggressive DLBCL showed that 80% of patients who took R-DA-EPOCH had an overall response, and the OS and PFS rates were 70% and 61%, respectively.

Primary Mediastinal B-Cell Lymphoma

• A retrospective analysis found that children and adults with primary mediastinal B-cell lymphoma who received R-DA-EPOCH had an estimated 3-year event-free survival of 86% and OS was 95%.

HIV-Associated Lymphoma

• In HIV-associated B-cell non-Hodgkin lymphoma, concurrent rituximab plus EPOCH yielded a 73% complete response rate, which is substantially higher than the approximately 50% seen with standard regimens like CHOP. One-year PFS rates were also higher for EPOCH-based regimens compared to historical CHOP data (up to 78% vs. 50%).

Burkitt Lymphoma

• Dose-adjusted R-EPOCH (DA-EPOCH-R) in adult Burkitt lymphoma showed a 2-year PFS rate of 84% and OS of 86%.

Other Lymphoma Subtypes

• Modified EPOCH regimens have also shown effectiveness in adult T-cell leukemia/lymphoma.
• A single-center study found that patients with aggressive T-cell lymphomas treated with EPOCH had a 60% CR rate, a PFS of about 8 months, and OS of about 20 months.

What Are the Common Side Effects?

EPOCH (and R-EPOCH) chemotherapy regimens are associated with a range of side effects, reflecting the intensity and multi-drug nature of the treatment. Side effects can vary in severity and timing, with some occurring during treatment and others emerging later.

Common side effects include:

• Low blood cell counts, including low white blood cells, red blood cells, and platelets
• Higher risk of infection and risk of reactivation of hepatitis B from rituximab
• Fatigue
• Nausea and vomiting
• Mouth sores
• Hair loss
• Peripheral neuropathy due to vincristine
• Decreased appetite
• Constipation or diarrhea
• Red or orange urine, sweat, or tears
• Trouble sleeping
• Heart problems, especially from doxorubicin
• Tumor lysis syndrome
• Infusion reactions, particularly with rituximab

Patients on EPOCH require close monitoring for these side effects, with supportive treatments such as growth factors, transfusions, antibiotics, and symptom management as needed. Prompt reporting of symptoms like fever, mouth sores, or unusual bleeding is critical.

Key Monitoring and Supportive Care Needs

Patients receiving EPOCH (or R-EPOCH) chemotherapy require comprehensive monitoring and proactive supportive care due to the regimen’s intensity and risk of serious side effects.

Monitoring

• Blood Counts: Frequent complete blood counts (CBC) are necessary before each cycle and at least twice weekly during treatment to monitor for neutropenia (low white blood cells), anemia (low red blood cells), and thrombocytopenia (low platelets). Dose adjustments for subsequent cycles are based on blood count results and patient tolerance.
• Organ Function: Kidney function, liver enzymes (AST/ALT), bilirubin, and electrolytes (calcium, magnesium, phosphate) should be checked before each cycle and as clinically indicated. Patients should also be monitored closely for lung toxicity and neurologic side effects.
• Cardiac Monitoring: Baseline and periodic assessment of left ventricular ejection fraction (LVEF) is recommended, especially for patients with cardiac risk factors, due to the risk of doxorubicin-induced cardiotoxicity.
• Infection Surveillance: Monitor for signs of infection, particularly during periods of neutropenia. Patients should be educated to report fever or symptoms promptly.
• Infusion Reactions: Monitor closely during rituximab and etoposide infusions for allergic or infusion-related reactions. Vital signs should be checked regularly.
• Tumor Lysis Syndrome: Monitor uric acid, kidney function, and electrolytes, particularly in patients with bulky disease or high tumor burden, to detect and manage tumor lysis syndrome early.

Supportive Care Needs

• Growth Factor Support: Prophylactic G-CSF (such as pegfilgrastim) is routinely given after each cycle to reduce the risk and duration of neutropenia.
• Infection Prophylaxis: Antibacterial prophylaxis (e.g., fluoroquinolones) may be used in high-risk patients, such as those with very low neutrophil counts or HIV-positive status. Antiviral and antifungal prophylaxis may be considered based on individual risk factors.
• Antiemetic Therapy: Scheduled anti-nausea medications (e.g., ondansetron) are given before and during chemotherapy to prevent and treat nausea and vomiting.
• Pre-medications for Infusion Reactions: Acetaminophen and diphenhydramine are given before rituximab to reduce the risk of allergic reactions.
• Hydration and Tumor Lysis Prophylaxis: IV fluids and medications like allopurinol may be used to prevent tumor lysis syndrome in patients with high tumor burden.
• Transfusions may be considered for severe anemia or thrombocytopenia as needed.

Patient Education and Safety

Patients should be educated on:

• Recognizing and promptly reporting symptoms of infection, bleeding, or infusion reactions.
• The importance of adhering to supportive medications and follow-up appointments.
• Infection prevention strategies at home during periods of low immunity.

Summary

EPOCH and R-EPOCH are multi-drug chemotherapy regimens designed to treat aggressive B-cell lymphomas. The addition of rituximab (R-EPOCH) enhances effectiveness for B-cell cancers. The regimens are administered in cycles, often with dose adjustments based on patient tolerance, and have demonstrated high efficacy in both standard and high-risk patient groups.

References

1. Alderuccio, J. P., et. al. 2018. DA-EPOCH-R for Adult Burkitt's Lymphoma: Pros and Cons. Journal of oncology practice, 14(11), 676–678. https://doi.org/10.1200/JOP.18.00624
2. Bartlett, N. L., et. al. 2019. 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. Journal of Clinical Oncology : official journal of the American Society of Clinical Oncology, 37(21), 1790–1799. https://doi.org/10.1200/JCO.18.01994
3. Cyclophosphamide injection [package insert]. Updated 2025. Hainan Poly Pharm. Co., Ltd. Accessed on May 20, 2025 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6fde2705-a2d8-4d48-9618-b9d99d051373
4. Dunleavy, K., et. al. 2018. Dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) in untreated aggressive diffuse large B-cell lymphoma with MYC rearrangement: a prospective, multicentre, single-arm phase 2 study. The Lancet. Haematology, 5(12), e609–e617. https://doi.org/10.1016/S2352-3026(18)30177-7
5. Etoposide injection [package insert]. Updated 2022. Fresenius Kabi USA, LLC. Accessed on May 20, 2025 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fe870629-104d-4d67-a7c6-f53bc588121e
6. Giulino-Roth, L., et. al. 2017. Outcomes of adults and children with primary mediastinal B-cell lymphoma treated with dose-adjusted EPOCH-R. British Journal of Haematology, 179(5), 739–747. https://doi.org/10.1111/bjh.14951
7. Healton, S. E., et. al. 2024. High Grade B-Cell Lymphoma with MYC/BCL6-Rearrangements (R) May Have Inferior Outcomes Compared to BCL2-R Disease. In: Blood. DOI: https://doi.org/10.1182/blood-2024-194144
8. Macmillan Cancer Support. 2023. Dose-adjusted (DA)-EPOCH +/- R. Accessed on May 20, 2025 at https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/dose-adjusted-epoch-rituximab
9. Maeda, Y., et. al. 2017. Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707. Haematologica, 102(12), 2097–2103. https://doi.org/10.3324/haematol.2017.167742
10. National Cancer Institute. 2023. R-EPOCH. Accessed on May 20, 2025 at https://www.cancer.gov/about-cancer/treatment/drugs/r-epoch
11. National Comprehensive Cancer Network. 2025. B-Cell Lymphomas. Accessed on May 20, 2025 at https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480
12. National Health Service. 2017. Dose Adjusted (DA)-EPOCH-R. Accessed on May 20, 2025 at https://www.swagcanceralliance.nhs.uk/wp-content/uploads/2020/10/DA-EPOCH-R1.pdf
13. Pejša, V., et. al. 2017. Rituximab with dose-adjusted EPOCH as first-line treatment in patients with highly aggressive diffuse large B-cell lymphoma and autologous stem cell transplantation in selected patients. Croatian medical journal, 58(1), 40–48. https://doi.org/10.3325/cmj.2017.58.40
14. Prednisone tablet [package insert]. Updated 2018. JUBILANT CADISTA PHARMACEUTICALS INC. Accessed on May 20, 2025 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e9d6774e-45f6-419f-b388-8dfb4dd34944
15. Rituxan [package insert]. Updated 2023. Genentech, Inc. Accessed on May 20, 2025 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b172773b-3905-4a1c-ad95-bab4b6126563
16. Sethi, T., et. al. 2021. EPOCH Is a Safe and Effective Treatment Option for Aggressive T-Cell Lymphomas. Blood. https://doi.org/10.1182/blood-2021-151238.
17. Sparano, J. A., et. al. 2021. Response-adapted therapy with infusional EPOCH chemotherapy plus rituximab in HIV-associated, B-cell non-Hodgkin's lymphoma. Haematologica, 106(3), 730–735. https://doi.org/10.3324/haematol.2019.243386
18. Tsukamoto, Y., et. al. 2020. Efficacy and Safety of the Modified EPOCH Regimen (Etoposide, Vincristine, Doxorubicin, Carboplatin, and Prednisolone) for Adult T-cell Leukemia/Lymphoma: A Multicenter Retrospective Study. Clinical lymphoma, myeloma & leukemia, 20(7), e445–e453. https://doi.org/10.1016/j.clml.2020.03.008
19. Vera de Jonge, A., et. al. 2023. DA-EPOCH-R for High Grade B-Cell Lymphoma Patients with MYC and BCL2 and/or BCL6 Rearrangements: Clinical Results of the Induction Phase of the HOVON-152 Trial In: Blood. DOI: https://doi.org/10.1182/blood-2023-181707
20. Vincristine injection [package insert]. Updated April 2024. Hospira. Accessed on May 20, 2025 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=49596de6-ab18-49d1-9e5b-30968fc21c36
21. Wilson, W. H., et. al. 1993. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 11(8), 1573–1582. https://doi.org/10.1200/JCO.1993.11.8.1573

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