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Treatment Name: FCR (Fludara­bine + Cyclophospha­mide + Rituximab)

FCR (Fludara­bine + Cyclophospha­mide + Rituximab) is a Chemotherapy Regimen for Chronic Lymphocytic Leukemia (CLL)

How does FCR work?
Each of the medications in FCR are designed to kill or slow the growth of leukemia cells.

F - Fludarabine
C - Cyclophosphamide (Cytoxan)
R - Rituximab (Rituxan)

Goals of therapy:
FCR is given to alleviate symptoms of CLL such as enlarged lymph nodes, enlarged liver or spleen, or symptoms of abnormal bone marrow function, such as frequent infection. FCR may not cure CLL, but frequently leads to long-term remission (3 or more years without signs or symptoms of CLL).

Schedule

  • Fludarabine intravenous infusion (I.V.) over 30 minutes on Days 1, 2, and 3
  • Cyclophosphamide I.V. over 30 minutes on Days 1, 2, and 3
  • Rituximab I.V. on Day 1.  The time of infusion varies depending on tolerability.  

Estimated total infusion time for this treatment:

  • Up to 6 hours for Cycle 1, Day 1; as short as 3 hours for the first day of next cycles if well tolerated
  • Infusion times are based on clinical studies, but may vary depending on doctor preference or patient tolerability.  Pre-medications and intravenous (I.V.) fluids, such as hydration, may add more time

Click here for common starting doses

FCR is repeated every 28 days. This is known as one Cycle. Each cycle may be repeated up to 6 times, depending upon the stage of the disease. Duration of therapy may last up to 6 months, depending upon response, tolerability, and number of cycles prescribed.

FCR is usually given in an outpatient infusion center, allowing the person to go home afterwards. On occasion, FCR may be given in the hospital if someone is too sick to go home after treatment. Often, the first day of treatment can take upwards of 6 hours.

Side Effects

In a multi-drug regimen, each medication has unique side effects. When these medicines are given together, drug-related side effects reported in clinical studies give the best estimate of what to expect. In clinical studies the most commonly reported side effects with FCR are shown here. Side effects sometimes have percentage ranges [example: low white blood cells 34 – 42%] because they differed between clinical studies:

On average, 17 - 26% of patients discontinue FCR due to unacceptable side effects.

The exact incidence of hair loss or neutropenic fever after FCR chemotherapy were not reported in the original studies, but may occur

Side effect videos Side Effect Videos
Nausea and VomitingNausea and VomitingFatigue Fatigue ConstipationConstipationAnemiaAnemiaDiarrheaDiarrheaBleedingBleedingHair LossHair LossNeutropenic FeverNeutropenic Fever

Monitoring

How often is monitoring needed?
Labs (blood tests) may be checked before treatment and periodically throughout treatment. Pre-treatment labs often include: Hepatitis B screening, Human Immunodeficiency Virus (HIV) screening, Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), uric acid, lactate dehydrogenase (LDH), plus any others your doctor may order.

How often is imaging needed?
Imaging may be checked before treatment, which commonly include a computerized tomography (CT) scan. There may be other scans if necessary.

How might blood test results/imaging affect treatment? 
Depending upon the results, your doctor may advise to continue chemotherapy as planned, or delay or switch therapy if it is not working.

ChemoExperts Tips

  • Pre-medications may be given before rituximab to help avoid infusion related reactions, these include: diphenhydramine (Benadryl®), acetaminophen (Tylenol®), and hydrocortisone (Solu-Cortef®)
  • The first dose of rituximab is often the most difficult, or takes the longest to infuse. It may lead to fever, shaking, and chills even if “pre-medications” are given to help prevent these side effects. Side effects generally go away when the rituximab is stopped. It may be restarted at a slower rate. Most patients are able to receive the entire dose, although it may take longer. If rituximab is well tolerated, it may be infused over 90 minutes
  • Allopurinol may be prescribed for the first cycle of chemotherapy to help prevent tumor lysis syndrome
  • An antiviral agent such as acyclovir (Zovirax®), valacyclovir (Valtrex®), or famciclovir (Famvir®) may be used to prevent reactivation of herpes simplex virus (HSV) or varicella zoster virus (VZV)
  • Typically, filgrastim (Neupogen®) or pegfilgrastim (Neulasta®) is given after chemotherapy to stimulate production of white blood cells and avoid periods of low white blood cell count (neutropenia) and infections
  • A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
  • Clinical trials may exist for Lymphoma. Ask your doctor if any studies are currently enrolling in your area. If not, go to clinicaltrials.gov to search for other centers offering study medications

Patient Assistance & Co-payment Coverage

Patients under the age of 65 years, or those with private insurance plans:
If you have insurance and are looking for patient assistance or copay assistance for FCR (Fludara­bine + Cyclophospha­mide + Rituximab), we have provided links that may help.

Visit our Patient Assistance page and click the links to various patient assistance programs for help paying for FCR (Fludara­bine + Cyclophospha­mide + Rituximab). Depending upon your income, they may be able to help cover the cost of:

  • Fludarabine
  • Cyclo­phospha­mide IV
  • Rituximab

For Branded medications (may be available for generic medications too), check with the manufacturer to determine if a co-pay card is offered and if it could reduce your monthly copay.

  • If you are uninsured, check with the manufacturer to determine if you are eligible to receive medication at no cost.

Medicare and Medicaid patients (Patients 65 years or older):
The clinic providing treatment will likely pre-authorize medications and immune therapies such as FCR (Fludara­bine + Cyclophospha­mide + Rituximab) and are the best source to help you understand drug cost.

  • Ask to speak with a patient assistance technician or financial counselor at the clinic or hospital administering this therapy.

Emotional Wellness

What is Emotional Wellness?
Emotional wellness is having a positive outlook balanced with a realistic understanding of current life events. This requires both an awareness and acceptance of your emotions. It is with this knowledge that you can develop a plan to take the necessary actions to positively impact your life.

Emotional wellness uses an ongoing process to continually reflect on the stressors of life in a constructive manner to move forward and create happiness.

Because emotional wellness is deeply connected with physical, social, and spiritual wellness, pursuing it often becomes particularly difficult in times of major illness. Despite this difficulty, working toward emotional wellness has been connected to improved treatment outcomes and a higher likelihood of achieving goals of therapy.

Learn more about pursuing emotional wellness while receiving treatment with FCR (Fludara­bine + Cyclophospha­mide + Rituximab)

Individual Drug Label Information

Fludarabine (Fludara®)

  • Fludarabine is an intravenous infusion
  • Dosage adjustments may be required for decreased kidney function
  • Fludarabine can severely suppress bone marrow function resulting in very low white blood cells, low red blood cells, and low platelets
  • There have been reported cases of production of antibodies against red blood cells or platelets causing them to be destroyed. This can result in severe low red blood cell or platelet counts. Patients on fludarabine should be monitored for a condition called “hemolysis” or destruction of blood cells
  • Rare cases of neurological effects such as confusion, irritability, blindness, seizures, coma, or evendeath have occurred
  • Fludarabine should be avoided during pregnancy and breastfeeding
  • Can cause low white blood cells known as “CD4+ T-cells” leading to an increased risk of developing Pneumocystis Pneumonia. Medications that prevent Pneumocystis Pneumonia, such as Bactrim® (sulfamethoxazole/trimethoprim), may be used
General Fludarabine (Fludara) Side Effects
  • Low white and red blood cell count
  • Weakness and fatigue
  • Low platelet cell count 
  • Fever and infections due to low white blood cell count
  • Nausea and vomiting
  • Diarrhea and intestinal bleeding
  • General body pain
  • Mouth sores - stomatitis
  • Decreased appetite
  • Confusion
  • Nerve pain
  • Lung problems: cough, shortness of breath, bleeding in lungs, lung infections
  • Skin rash
  • Heart problems, heart swelling
  • Click on the fludarabine (Fludara) package insert below for reported side effects and possible drug interactions

Side Effect Videos
DiarrheaDiarrheaFatigue Fatigue BleedingBleedingPainPainAnemiaAnemiaNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Cyclo­phospha­mide IV (Cytoxan®)

  • Cyclophosphamide is administered as an intravenous (I.V.) infusion
  • May decrease the ability to become pregnant. Fertility preservation is recommended in couples wishing to become pregnant.
  • A smaller dosage may be required for patients receiving hemodialysis
  • Has been linked to the development of other cancers in a small number of people
General Cyclophosphamide (Cytoxan) Side Effects
  • Low white blood cell count which can increase the risk of infection
  • Nausea or vomiting, which can be acute (first 24 hours) or delayed (Days 2 – 5)
  • Hair loss, which is usually reversible
  • Click on the cyclophosphamide (Cytoxan) package insert below for reported side effects and potential drug Interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingHair LossHair LossNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Rituximab (Rituxan®)

  • Rituximab is an intravenous infusion
  • Acetaminophen (Tylenol®) and antihistamines (e.g. diphenhydramine = Benadryl®) should be given prior to each dosePatients should be screened for hepatitis B as rituximab can cause a re-activation of this infection
  • May cause vaccines to work less well. It is advised that vaccines be given two to four weeks prior to rituximab if possible
General Rituximab (Rituxan) Side Effects
  • May cause an infusion reaction, which could include skin reaction, shaking, chills, fever, or shortness of breath. These reactions may be severe, but are very rarely life-threatening
  • Infusion reactions does not usually happen after the first dose, but are possible
  • May increase the risk of infection. Your doctor may prescribe antibiotics to prevent certain infections associated with rituximab use
  • Click on the rituximab (Rituxan) package insert below for reported side effects and potential drug Interactions
See DailyMed package insert.

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References

1. Robak T, Dmoszynska A, Solal-Céligny P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol 2010;28(10):1756-65.

2. Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010;376(9747):1164–74.

Created: October 1, 2015 Updated: September 10, 2018

What is Chronic Lymphocytic Leukemia (CLL)?

Chronic Lymphocytic Leukemia (CLL) is the most common type of leukemia diagnosed in adults. It is a cancer of the B-lymphocyte. In rare cases, CLL may be hereditary, but most causes are unknown. The stage of CLL can vary at diagnosis and throughout treatment. Stages of CLL include Rai stage 0, I, II, III, or IV. Many therapies are not curative, however, newer therapies are able to suppress the cancer for many months or even years.

Medications for CLL may include intravenous infusions, oral tablets or capsules, or a combination of IV and oral medications. Patients may be diagnosed with CLL without having any symptoms. Others may go to their doctor with symptoms of fatigue, a large spleen, or decreased appetite. The effectiveness of the treatment may depend upon the stage at diagnosis.

NOTE: Treatment Options listed below are not all-inclusive. Other treatments may be available. ChemoExperts provides drug information and does not recommend any one treatment over another. Only your Doctor can choose which therapy is appropriate for you.

Clinical Studies

If you are interested in reading the clinical trials results, please click on references below:

1. Robak T, Dmoszynska A, Solal-Céligny P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol 2010;28(10):1756-65.

2. Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010;376(9747):1164–74.

Common starting doses

  • Fludarabine 25 mg/m2 IV over 30 minutes on Days 1, 2, and 3
  • Cyclophosphamide 250 mg/m2 IV over 30 minutes on Days 1, 2, and 3
  • Rituximab 375 mg/m2 IV on Day 1 of Cycle 1
  • Rituximab 500 mg/m2 IV on Day 1 of Cycles 2, 3, 4, 5, and 6

What is a CBC?

A Complete Blood Count (CBC) is a frequently ordered blood test that tells clinicians the status of your: 1) White blood cell count, 2) Hemoglobin, and 3) Platelet count at the time the test was taken.

Common uses:
1) White blood cell count (WBC): is used to determine infection risk, or response to chemotherapy. Certain chemotherapy agents may harm our good infection-fighting cells. Sometimes chemotherapy may need to be delayed to allow these cells to recover.

2) Hemoglobin: is used to determine if someone is anemic. Anytime the hemoglobin is below 12 g/dL, the person is said to be anemic. Red blood cell transfusions, and sometimes iron can be given to restore the hemoglobin level, but anemia treatment should always aim at treating the underlying cause or condition.

3) Platelet count: is used to determine if the risk of bleeding is increased or if a platelet transfusion is required to prevent bleeding. Certain medications that increase bleeding risk, such as: aspirin, certain chemotherapy agents, and blood thinners, may need to be stopped temporarily until the platelet count is within a safe range.

What is a CMP?

A Comprehensive Metabolic Panel (CMP) is a frequently ordered blood test that tells clinicians the status of your: 1) Electrolytes & Acid/Base status2) Kidney function, 3) Liver function, 4) Blood sugar, and 5) Calcium at the time the test was taken. It is commonly used to monitor liver and kidney function when beginning new medications such as chemotherapy. A total of 14 tests are run simultaneously and are shown below.

Electrolytes & Acid/Base status:
1) Sodium, 2) Potassium, 3) Carbon dioxide, 4) Chloride

Kidney Function:
5) BUN (blood urea nitrogen), 6) Serum creatinine (Scr)

Liver Function:
7) AST, 8) ALT, 9) Total bilirubin, 10) Alk Phos, 11) Albumin, 12) Total protein

Blood sugar:
13) Serum glucose

Calcium:
14) Serum calcium

What does Cure mean?

The word “cure” means there are no cancer cells left in the body and cancer will never come back. Depending on the cancer type and stage, this may be the true goal of therapy. However, it is very difficult to prove all cancer cells are gone. Even though images, like X-rays and MRI’s, and blood tests may not show any signs of cancer, there can be a small amount of cancer cells still left in the body. Because of this, the word “remission” is used more often. This means there are no signs or symptoms of cancer. Patients in remission are followed closely for any signs of cancer returning. Sometimes, more chemotherapy may be given while in remission to prevent the cancer from coming back.

Doctors usually do not consider a patient “cured” until the chance of cancer returning is extremely low. If cancer does return, it usually happens within 5 years of having a remission. Because of this, doctors do not consider a patient cured unless the cancer has not come back within 5 years of remission. The five-year cutoff does not apply to all cancers.