by Dr. C.H. Weaver M.D. 8/2021
Rituxan® (rituximab) combined with cyclophosphamide, doxorubicin, Oncovin® and prednisone (R-CHOP) is the standard treatment for many patients with Non-Hodgkin’s lymphoma (NHL). Although R-CHOP is the standard researchers continue to try to improve R-CHOP treatment either by adding additional drugs to the regimen in NHL patients at high risk of recurrence or be reducing the total treatment in low risk individuals. Most recently doctors from Germany have reported that 4 cycles of R-CHOP treatment is just is good as 6 cycles in certain low risk individuals.1 All NHL patients should understand the role of R-CHOP and the research being conducted to improve its effectiveness.
Frequently Asked Questions About R-CHOP
What is R-CHOP Chemotherapy?
CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) is a common treatment used for NHL that combines Rituxan immunotherapy with chemotherapy; it is referred to as R-CHOP and is a standard treatment option for NHL.
R-CHOP consists of the following drugs:
- Rituximab (Rituxan) Rituxan is a monoclonal antibody that has been designed to recognize and bind to B-cells. The binding of Rituxan stimulates the immune system to attack the B-cells and may also be involved in the direct killing or disabling of the B-cell.
- Cyclophosphamide (Cytoxan) is a chemotherapy drug that targets the DNA of cancer cells and signals them to stop dividing.
- Doxorubicin hydrochloride (Adriamycin) is a chemotherapy drug that blocks an enzyme cancer cells need to grow and reproduce.
- Vincristine (Oncovin, Vincasar, Vincrex) Vincristine is an alkaloid chemotherapy drug and is a vesicant, meaning it can damage tissues that it comes in contact with.
- Prednisolone a corticosteroid oral medication that works with your immune system to help reduce inflammation.
How is R-CHOP administered?
R CHOP is given in “cycles.” Each cycle begins with intravenous doxorubicin, vincristine and cyclophosphamide and is followed by oral prednisolone. Depending on the type of NHL patients will receive 4-8 cycles of R-CHOP. Cycles are typically administered every 21 days unless patients are receiving “dose dense” R-CHOP. Dose-dense R-CHOP is given every 14 days and is supported with a white blood cell growth factor to prevent low white blood counts, infection and fever.
Before each treatment a blood test is performed to check the white blood cell count and determine if the liver and kidneys are functioning well enough. If they’re not, the doctor may need to adjust the treatment.
What are the side effects of R-CHOP chemotherapy?
Chemotherapy is directed at killing or eradicating cancer cells. Unfortunately, cancer treatments may also damage normal, healthy cells that are not affected by the cancer. The result of this damage is a complication, or side effect, of treatment. Side effects occur because most cancer treatments cannot distinguish between cancer cells and normal, healthy cells. The main side effects of R-CHOP include the following. The most important side effect to understand is neutropenia or a low white blood count.
Common Side Effects Include:
- irritation around the intravenous or port site
- red or pink urine for a few days due to doxorubicin
- appetite changes
- weight changes
- sleeping difficulties
- low blood counts
- allergic reactions
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What Does the Research Show?
Four Cycles of R-CHOP can be Used to Treat Favorable Prognosis DLBCL
Standard therapy for young patients with favorable-prognosis diffuse large B-cell lymphoma (DLBCL) is six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) given every 21 days.1
New data from the FLYER clinical trial suggests that some patients can be spared two cycles of CHOP, with Rituxan still given over six cycles, and have excellent clinical outcomes, similar to those seen after the standard six cycles of R-CHOP.
In the FLYER clinical trial doctors from Germany treated 592 patients aged 18 to 60 years with “low risk” stage I/II DLBCL, with either six or four cycles of CHOP chemotherapy every 21 days plus the standard six cycles of Rituxan. “Low risk” was defined as an age-adjusted IPI of 0, age less than 60 and maximum disease diameter < 7.5 cm.
The 3-year progression-free survival with four cycles of CHOP was 96% compared to 94% seen with six cycles of CHOP, and overall survival was 99% and 98% respectively.
The authors concluded that low risk DLBCL patients can be spared two cycles of chemotherapy which reduces the average time on treatment from 126 to 84 days.
It’s important to understand that the results do not apply to the majority of patients with DLBCL and the results should not be applied to individuals over the age of 60.
Dose-Dense R-CHOP for Non-Hodgkin Lymphoma
Among patients with NHL supportive treatment with Neulasta® (pegfilgrastim) allows for the safe administration of the dose-dense treatment regimen R-CHOP-14 given every 14 days.
Dose-dense chemotherapy is a treatment approach where chemotherapy is administered as frequently as possible with the goal of delivering the greatest amount of chemotherapy over the shortest period of time, thereby delivering the maximum amount of chemotherapy drug to the cancer. Increasing the dose and frequency of chemotherapy administration appears to increase survival in some patients with non-Hodgkin’s lymphoma because dose-dense regimens may kill more cancer cells, but they also allow less time for bone marrow recovery and are associated with anemia (low red blood cell level) and neutropenia (low white blood cell level).
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Neutropenia increases susceptibility to infection and can become a serious condition for several reasons: Many patients who develop neutropenia will require a delay in treatment or a dose reduction (both events can prevent them from receiving full benefits of treatment); patients who develop neutropenia may require hospitalization; and even minor infections can become life-threatening. Neulasta is a drug that is used to stimulate the production of immune cells in order to reduce or prevent neutropenia.
In order to evaluate the R-CHOP-14 researchers in Italy conducted a phase II clinical trial among 50 patients with DLBCL. Neulasta was given on the third day of each treatment cycle.
- 92% of treatment cycles were delivered on time.
- Severe (grade 4) neutropenia developed in 19% of treatment cycles and fever developed in 4% of treatment cycles.
- 74% of patients experienced a complete remission following treatment.
- After two years, overall survival was 68%.
The researchers conclude that a single dose of Neulasta in each treatment cycle allowed most patients with diffuse large B-cell lymphoma to receive their chemotherapy on time, with few cases of febrile neutropenia.
Six Cycles of R-CHOP-14 Remains Standard of Care for Elderly with Diffuse Large B-cell Lymphoma
Among elderly patients with diffuse large B-cell lymphoma, treatment with six cycles of Rituxan® and CHOP-14 produces better outcomes than CHOP-14 alone and may also produce better outcomes than eight cycles of Rituxan and CHOP-14.
To compare different approaches of administering CHOP with or without Rituxan in the treatment of elderly patients with diffuse large B-cell lymphoma, researchers in Germany conducted a study among more than 1,000 patients between the ages of 61 and 80 years.
Study participants were assigned to receive either six or eight cycles of CHOP administered every two weeks (CHOP-14). Half the patients also received Rituxan.
- The addition of Rituxan improved outcomes compared to CHOP-14 alone.
- Patients who received six cycles of Rituxan and CHOP-14 appeared to have the best overall survival.
The researchers concluded that six cycles of Rituxan and CHOP-14 appeared to produce the best outcomes in the treatment of elderly patients with diffuse large B-cell lymphoma.3
A study published in the New England Journal of Medicine provides further evidence that long-term survival may be improved with the addition of Rituxan™ to the chemotherapy combination consisting of cyclophosphamide, doxorubicin, Oncovin® and prednisone in elderly patients with aggressive B-cell non-Hodgkin’s lymphoma.
NHL is a cancer of the lymph tissue, which is part of the body’s immune system. Lymph tissue is present in lymph nodes, lymph vessels, blood and bone marrow, which exist throughout the body. It is also present in organs such as the thymus, tonsils and spleen. The main cells in the lymph system are lymphocytes, of which there are two types: B and T-cells. Each of these cells has a very specific function in aiding the body to fight infection. The large majority of NHL cases involves cancer of the B-lymphocytes and characterized by the excessive accumulation of these atypical cells. This results in overcrowding of blood and lymph tissue, suppressing the formation and function of blood and immune cells that are normally present. Additionally, the cancerous lymphocytes themselves do not function normally, leading to a further decrease the body’s ability to fight infection. The standard chemotherapy combination for elderly patients with this disease consists of cyclophosphamide, doxorubicin, Oncovin® and prednisone, often called CHOP.
Rituxan™ is a monoclonal antibody that has shown promising results when used in the treatment of some hematologic (blood/lymph) cancers. Monoclonal antibodies are proteins that can be made in the laboratory and are designed to recognize and bind to very specific cells. Rituxan™ is a monoclonal antibody that binds to proteins on the surface of B-lymphocytes, thereby stimulating the immune system to attack and kill the cancerous B-cells. A significant benefit of this approach is that Rituxan™ only targets cancer cells (B-cells), thus sparing healthy cells from destruction. This is in contrast to chemotherapy or radiation, which do not differentiate between cancer cells and healthy cells in the body, a characteristic leading to potentially destructive side effects. Studies have demonstrated that the combination of Rituxan™ and chemotherapy produces outcomes superior to chemotherapy alone for some types of NHL, and is the standard treatment for these diseases in younger patients.
A large clinical trial evaluating CHOP plus Rituxan™ in elderly patients (over 60 years) previously demonstrated that this treatment regimen improved anti-cancer responses and survival compared to CHOP alone as initial therapy. The researchers that conducted this trial have recently reported longer follow-up data of these patients. Eighteen months following treatment, the rate of cancer-free survival was 76% for patients treated with CHOP plus Rituxan™, compared to only 64% for patients treated with CHOP alone. Two years following treatment, 57% of patients treated with CHOP plus Rituxan™ did not experience progression of cancer, compared to only 37% of patients treated with CHOP alone. Overall survival at two years after therapy was 70% in the group of patients treated with CHOP plus Rituxan™, compared to only 57% in the group of patients treated with CHOP alone. The addition of Rituxan™ to the treatment regimen was well tolerated in these elderly patients.
These results clearly demonstrate that the combination of Rituxan™ plus CHOP may increase long-term cancer-free survival and overall survival in elderly patients compared to the treatment of CHOP alone for aggressive NHL. Clinical trials are also ongoing to determine the optimal dose and duration of Rituxan™ therapy in combination with chemotherapy. Although Rituxan™ has proven in clinical trials to benefit patients with aggressive NHL when used in combination with CHOP, 40% of eligible NHL patients are still not being offered treatment with Rituxan™.4
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- American Society of Hematology (ASH) 2018. Presented December 2, 2018. Abstract 781.
- Pfreundschuh M, Kloess M, Zeynalova S, et al. Six vs. eight cycles of bi-weekly CHOP-14 with or without rituximab for elderly patients with diffuse large B-cell lymphoma (DLBCL): Results of the completed RICOVER-60 trial of the German High-Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL).Blood. 2006;108;64a. Abstract 205.
- Brusamolino E, Rusconi C, Montalbetti et al. Dose-Dense R-CHOP-14 Supported by Pegfilgrastim in Patients with Diffuse Large B-Cell Lymphoma: A Phase II Study of Feasibility and Toxicity. Haematologica. 2006;91:496-502.
- New England Journal of Medicine, Vol 346, No 4, pp 235-242, 2002