CHOP and R-CHOP are cornerstone chemotherapy regimens for treating indolent and aggressive non-Hodgkin lymphomas, including diffuse large B-cell lymphoma (DLBCL). The CHOP chemotherapy regimen combines four medications (cyclophosphamide, doxorubicin, vincristine, and prednisone), while R-CHOP adds a targeted monoclonal antibody called rituximab. The purpose of these medications is to kill cancer cells and reduce lymphoma progression.

What Does CHOP Stand For?

CHOP stands for:

• Cyclophosphamide – an alkylating agent
• Hydroxydaunorubicin / doxorubicin – an anthracycline
• Oncovin (vincristine) – a mitotic inhibitor
• Prednisone / prednisolone – a corticosteroid

Cyclophosphamide, doxorubicin, and vincristine are chemotherapy drugs that work to destroy cancer cells. Prednisone is a steroid that stops cancer cells from growing and kills them. This regimen is used as standard chemotherapy treatment for aggressive NHL and T-cell lymphomas.

What Is R-CHOP and How Is It Different?

R-CHOP contains all of the medications in the CHOP regimen, plus rituximab. Rituximab is a targeted immunotherapy agent that is added to CHOP to improve outcomes. It works by targeting a protein called CD20 on B-cells, which helps the immune system destroy these B-cells. R-CHOP is primarily used for diffuse large B-cell lymphoma (DLBCL) and other CD20+ B-cell NHLs.

How Are CHOP and R-CHOP Given?

Both regimens are administered in 21-day cycles, known as CHOP-21 and R-CHOP21.
Cyclophosphamide, doxorubicin, vincristine, and rituximab are given intravenously. You may receive these medications through a cannula, PICC line, central line, or implantable port. Prednisone is taken by mouth for the first 5 days of each cycle.

To prevent infusion-related reactions, your healthcare provider may give you pre-medications such as acetaminophen, an antihistamine, and a steroid. Antiemetics may be given to prevent nausea and vomiting.

A typical treatment course is 6–8 cycles, depending on disease stage and type. Below are examples of a 21-day CHOP and R-CHOP cycle.

CHOP Cycle

• Day 1: Intravenous cyclophosphamide, doxorubicin, and vincristine.
• Days 1–5: Oral prednisone.
• Days 6–21: Recovery period.

R-CHOP Cycle

• Day 1: Rituximab infusion followed by CHOP drugs.
• Days 2–5: Oral prednisone.
• Days 6–21: Recovery, often with G-CSF injections to boost white blood cells.

How Effective Are CHOP and R-CHOP?

CHOP and R-CHOP are standard chemotherapy regimens for treating B-cell lymphomas, especially diffuse large B-cell lymphoma. R-CHOP is generally more effective than CHOP, particularly in improving survival and response rates. The effectiveness of CHOP and R-CHOP has been extensively studied in clinical trials and real-world practice.

CHOP has been a standard treatment for intermediate- and high-grade non-Hodgkin lymphomas for decades. However, outcomes can be improved with additional treatments such as radiotherapy or rituximab (R-CHOP).

In advanced-stage disease, CHOP achieves cure rates of about 30–40% in national cooperative group trials, with 3-year overall survival rates around 52% and disease-free survival rates near 41%. R-CHOP is the gold standard for DLBCL, with 50–70% cure rates.

• Non-Hodgkin’s Lymphoma: CHOP alone provides substantial benefit, but combining three cycles of CHOP with involved-field radiotherapy results in higher 5-year progression-free survival (77% vs. 64%) and overall survival (82% vs. 72%) compared to CHOP alone for localized intermediate- and high-grade cases.
• Diffuse Large B-Cell Lymphoma (DLBCL)
  • In older patients, adding rituximab to CHOP (R-CHOP) significantly improves failure-free survival compared to CHOP alone (53% vs. 46% at 3 years) and reduces the risk of treatment failure and death.
  • A long-term study showed that the 10-year progression-free survival (PFS) with R-CHOP is 36% vs. 20% with CHOP alone. Additionally, 10-year overall survival (OS) is 43% with R-CHOP vs. 28% with CHOP.
• Advanced Chronic Lymphocytic Leukemia: In poor prognosis patients, CHOP significantly improves 2-year survival rates (77% vs. 44%) and disease status compared to COP (a similar regimen without doxorubicin).

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What Are the Side Effects of CHOP/R-CHOP?

CHOP and R-CHOP are associated with a range of side effects, some common and others rare or serious. Most side effects are similar for both regimens, but R-CHOP includes additional risks related to rituximab.

Shared Side Effects

Since CHOP and R-CHOP contain four of the same medications, they share many side effects. Side effects of both regimens may include:

• Fatigue
• Nausea
• Stomach pain
• Loss of appetite
• Hair loss
• Low blood cell counts
• Infection risk
• Mouth sores
• Constipation
• Diarrhea
• Red or pink urine
• Numbness, tingling, or pain in the hands and feet
• High blood sugar
• Hand-foot syndrome
• Fluid retention
• Pain along the vein

Specific and Serious Side Effects

Some side effects are specific to certain medications in the regimen:

• Allergic reactions: Rituximab (in R-CHOP) can cause infusion reactions, including rash, itching, swelling, breathing difficulties, fever, and chills. These are most common during the first infusion and are closely monitored.
• Heart problems: Doxorubicin and cyclophosphamide can increase the risk of heart failure or other cardiac issues, especially with higher cumulative doses. Rituxan can cause arrhythmias. A baseline cardiac evaluation is recommended, followed by regular monitoring during treatment.
• Tumor lysis syndrome: Rapid destruction of cancer cells can lead to metabolic imbalances, potentially harming the kidneys and causing muscle cramps, irregular heartbeat, or seizures.
• Secondary cancers: There is a small risk of developing other cancers, such as leukemia, years after treatment.
• Infertility: Both regimens may affect fertility, sometimes permanently.
• Mood changes and trouble sleeping: Steroids like prednisone can cause mood swings, insomnia, and increased blood sugar.
• Other rare effects: These include severe skin reactions, inflammation of blood vessels, kidney problems, lung problems, and, very rarely, neurological complications.
• Harm to babies: CHOP and R-CHOP can cause harm to unborn babies, and are not recommended during pregnancy.

Managing Side Effects

Most side effects are temporary and resolve after treatment ends, but some (such as nerve damage or fertility issues) may be long-lasting. Supportive medications and close monitoring help manage many of these risks. It is important to report any new or worsening symptoms to your healthcare team promptly, as some side effects can be serious or life-threatening.

Who Receives R-CHOP vs CHOP Alone?

R-CHOP is standard of care for most patients with B-cell NHL expressing CD20, including DLBCL and follicular lymphoma, as rituximab targets the CD20 antigen found on B-cells. CHOP alone may be considered for patients with contraindications to rituximab, such as:

• Non–B-cell lymphomas (e.g., T-cell lymphomas), since rituximab is ineffective against non–CD20-expressing cells.
• Severe hypersensitivity to rituximab or its components.
• Certain comorbidities or clinical situations where rituximab poses unacceptable risk, though this is uncommon.

Biopsy and immunophenotyping are critical steps in determining the appropriate chemotherapy regimen-specifically, whether a patient should receive CHOP or R-CHOP:

• A tissue biopsy provides the definitive diagnosis of lymphoma and allows for the assessment of the tumor's morphology and architecture. This is the cornerstone for establishing the type of lymphoma, which is necessary before any treatment decisions can be made.
• Immunophenotyping identifies the specific antigens (such as CD20) expressed on the surface of lymphoma cells, which determines the lineage (B-cell vs T-cell) and can help guide therapy.

Summary

CHOP and R-CHOP are two chemotherapy regimens. CHOP contains cyclophosphamide, doxorubicin, vincristine, and prednisone, while R-CHOP adds rituximab. R-CHOP is the standard treatment for most patients with B-cell non-Hodgkin lymphomas, especially DLBCL, due to its superior efficacy. CHOP alone is typically reserved for rare cases where rituximab cannot be used, or for non–B-cell lymphomas where rituximab is ineffective. Common side effects include hair loss, fatigue, nausea, increased infection risk, and blood count changes. R-CHOP adds the risk of allergic reactions from rituximab.

References

1. Boyd, S. D., et. al. 2013. Selective immunophenotyping for diagnosis of B-cell neoplasms: immunohistochemistry and flow cytometry strategies and results. Applied immunohistochemistry & molecular morphology : AIMM, 21(2), 116–131. https://doi.org/10.1097/PAI.0b013e31825d550a
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4. Coiffier, B., et. al. 2010. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood, 116(12), 2040–2045. https://doi.org/10.1182/blood-2010-03-276246
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8. EviQ. 2021. Non-Hodgkin lymphoma R-CHOP21 (rituximab CYCLOPHOSPHamide DOXOrubicin vinCRISTine prednisolone). Accessed on May 12, 2025 at https://www.eviq.org.au/haematology-and-bmt/lymphoma/other-b-cell-lymphoma/70-r-chop21-rituximab-cyclophosphamide-doxorubici
9. Fisher, R. I., et. al. 1993. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. The New England journal of medicine, 328(14), 1002–1006. https://doi.org/10.1056/NEJM199304083281404
10. French Cooperative Group on Chronic Lymphocytic Leukaemia. 1986. EFFECTIVENESS OF "CHOP" REGIMEN IN ADVANCED UNTREATED CHRONIC LYMPHOCYTIC LEUKAEMIA. In: The Lancet. PMID: 2872470
11. Leukemia & Lymphoma Society. Treatment for Aggressive NHL Subtypes. Accessed on May 12, 2025 at https://www.lls.org/lymphoma/non-hodgkin-lymphoma/nhl-subtypes/treatment-aggressive-nhl-subtypes
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13. Meng, F., et. al. 2015. Efficacy and safety of rituximab combined with chemotherapy in the treatment of diffuse large B-cell lymphoma: a meta-analysis. International journal of clinical and experimental medicine, 8(10), 17515–17522. PMCID: PMC4694242  PMID: 26770342
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