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Treatment Name: HyperCVAD (Part A)

HyperCVAD (Part A) is a Chemotherapy Regimen for Acute Lymphoid Leukemia (ALL)

Hyper - Hyperfractionated 
C - Cyclophosphamide 
V - Vincristine 
A - Adriamycin (doxorubicin) 
D - Dexamethasone

Alternative names: hypercvad, hyper-cvad, hyper cvad

How does HyperCVAD chemotherapy work?
Each of the medications in HyperCVAD (Part A) are designed to kill cancer cells in the blood stream and bone marrow.

Goals of therapy:
Hyper CVAD is given to eliminate leukemia cells from the body and to decrease symptoms from ALL, such as bleeding, bruising, and recurrent infections. HyperCVAD is commonly given with the goal of cure.

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Schedule

  • Cyclophosphamide intravenous (I.V.) infusion, usually given over three hours, every 12 hours (twice daily) on Days 1,2,3 (six doses total)
  • Mesna I.V. infusion, usually given over 24 hours on Days 1,2,3, ending on Day 4
  • Vincristine I.V. infusion, usually given over 15 minutes on Days 4 and 11
  • Doxorubicin I.V. infusion, given over 2 - 24 hours (infusion time depends upon hospital guidelines) on Day 4
  • Dexamethasone 40 mg (ten 4 mg oral tablets) by mouth on Days 1,2,3,4 and 11,12,13,14

Mesna is not a chemotherapy agent. It binds to a toxic metabolite of cyclophosphamide called acrolein.

Click here for common hyper cvad starting doses, or click on the clinical study references at the bottom of this page.

HyperCVAD Part A usually requires a 4 - 5 day stay in a hospital. Typically, cyclophosphamide, doxorubicin, vincristine, and dexamethasone are all given in the hospital on Days 1 - 4 of each cycle. Vincristine may be given in the clinic on Day 11 and dexamethasone is usually taken at home on Days 11 - 14. Often, the first cycle of treatment may require a 15 - 20 day stay in a hospital (or sometimes longer), depending upon how well the side effects are tolerated. Patients usually go home once their white blood cell count returns to the normal range.

HyperCVAD Part A is alternated with HyperCVAD Part B every 21 days. This sometimes takes longer if waiting for normal blood counts recover after the previous cycle. When both Part A and Part B are completed, this is known as one Cycle.

  • Each cycle may be repeated up to four times, depending upon the stage of the disease.
  • Duration of therapy may last up to eight months, depending upon response, tolerability, and number of cycles prescribed.
  • On occasion, your doctor may choose to start with Part B, instead of Part A.

In some cases of ALL, two pieces of two chromosomes trade small sections of their DNA forming what is known as the “Philadelphia Chromosome."

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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 HyperCVAD (Part A) are shown here. Side effects sometimes have percentage ranges [example: 7 – 8% experience mood changes] because they differed between clinical studies:

  • Infection (10%),
  • Fever (8%),
  • Mood changes (7 - 8%),
  • Mouth sores (2%),
  • Diarrhea (1 - 2%).

Side effect videos Side Effect Videos
DiarrheaDiarrheaPainPainNeutropenic FeverNeutropenic FeverAnemiaAnemiaBleedingBleedingHair LossHair LossFatigue Fatigue ConstipationConstipationNausea and VomitingNausea and Vomiting

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Monitoring

How often monitoring needed?
Labs (blood tests) will be checked before treatment, daily while in the hospital, then periodically in the outpatient clinic. Labs often include: 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 or during the first month of therapy if there is concern for a blood clot or infection. Imaging may include: X-rays or computerized tomography (CT) scans.

How might blood test results/imaging affect treatment?
Depending upon the bone marrow results after the first cycle of Hyper CVAD chemo (Part A), your doctor may advise to continue chemotherapy as planned or switch to a different therapy.

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ChemoExperts Tips

  • Drink plenty of fluids (1-2 liters/day), especially during Days 1-3 when cyclophosphamide is given. This will help flush the bladder and avoid toxicity from acrolein build-up in the bladder
  • Allopurinol may be prescribed for the first cycle of chemotherapy to help prevent tumor lysis syndrome
  • Typically, filgrastim (Neupogen®) or pegfilgrastim (Neulasta®) is given after chemotherapy to stimulate production of white blood cells and avoid periods of neutropenia
  • Antibiotics, antifungal agents, and antiviral medications are commonly used to prevent infection. Be sure to tell your doctor if you experience discomfort anywhere as this may be a symptom of an infection
  • A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
  • Clinical trials may exist for ALL. 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 HyperCVAD (Part A), 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 HyperCVAD (Part A). Depending upon your income, they may be able to help cover the cost of:

  • Cyclo­phospha­mide
  • Vincristine
  • Doxorubicin
  • Dexamethasone

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 HyperCVAD (Part A) 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 HyperCVAD (Part A)

Individual Drug Label Information

Cyclo­phospha­mide (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.

Vincristine (Oncovin®)

  • ​Vincristine MUST only be given by intravenous infusion. May NOT be administered any other way
  • Dosage may be reduced in patients with poor liver function
  • May interact with certain antifungal medications
  • Vincristine will cause death if administered into spinal fluid
General Vincristine (Oncovin) Side Effects
  • Nerve pain in hands or feet may increase after each dose. It is usually reversible if treatment is stopped or dose is adjusted
  • Hair loss is NOT common if vincristine is given by itself
  • May cause constipation; preventative medicines may help decrease or avoid constipation
  • Leakage into skin or surrounding muscle may cause severe irritation (extravasation)
  • Click on the vincristine (Oncovin) package insert below for reported side effects and potential drug interactions

Side Effect Videos
ConstipationConstipationPainPain

See DailyMed package insert.

Doxorubicin (Adriamycin®)

  • Doxorubicin is administered as an intravenous infusion and is red in color
  • Can affect heart function. A heart study (echocardiogram) may be required before receiving the first dose
  • Dosage may be reduced in patients with poor liver function
  • Has been linked to the development of other cancers in a small number of people (1.5% chance at 10 years)
General Doxorubicin (Adriamycin) Side Effects
  • Nausea, vomiting, diarrhea, and mouth sores (stomatitis)
  • Leakage into skin or surrounding muscle during infusion may cause severe irritation (extravasation)
  • May temporarily turn urine orange
  • Hair loss, which is usually reversible
  • Increased risk of infection due to decrease white blood cell count (neutropenia)
  • Click on the doxorubicin (Adriamycin) package insert for reported side effects and possible drug interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaHair LossHair LossPainPainNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Dexamethasone (Decadron®)

  • Dexamethasone is supplied as an oral tablet or oral liquid
  • Dexamethasone may increase the risk of infection. Depending upon how much dexamethasone is taken, antibiotics may be prescribed to help prevent infection
  • Should be taken with food and with a large glass of water to avoid stomach irritation or ulcers
  • Should be taken before 6 p.m. when possible, to avoid trouble falling asleep
  • May decrease the response to vaccines; vaccines may need to be repeated at a later date to obtain maximal response
  • If taken daily for several days or weeks, the dose of dexamethasone may need to be gradually decreased (tapered) to avoid withdrawal symptoms
  • If you miss a dose, take the next dose as soon as possible
  • Should be stored at room temperature
General Dexamethasone (Decadron) Side Effects
  • May cause high blood sugar, weight gain, irritability, high blood pressure, difficulty sleeping, stomach ulcers, bone loss, muscle weakness
  • Click on the dexamethasone (Decadron) package insert below for reported side effects and potential drug Interactions
See DailyMed package insert.

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References

1. Kantarjian HM, O'Brien S, Smith TL, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult lymphocytic leukemia. J Clin Oncol. 2000;18:547-561.

2. Kantarjian H, Thomas D, O'Brien S, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004;101:2788-2801.

3. Thomas DA, Faderl S, O'Brien S, et al. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006;106:1569-1580.

Created: August 29, 2015 Updated: February 10, 2016

What is Acute Lymphoid Leukemia (ALL)?

Acute Lymphoid Leukemia (ALL), also known as acute lymphoblastic leukemia, is a disease of the lymphoid cells found in the bone marrow. Lymphoid cells are responsible for developing into cells of the immune system called B-cells, T-cells, or Natural Killer cells. In ALL, immature lymphoid cells know as "blasts" replicate at a very fast rate. Sometimes blasts crowd out the normal cells in the bone marrow so that red blood cells or platelets are unable to develop.

Common symptoms of ALL include fatigue, infection, and bruising or bleeding. ALL is the most common cancer diagnosed in children, but is rare in adults. Most cases of ALL are considered "de novo" meaning that the cause is unknown; however, some cases can be linked to certain genetic syndromes. There is no staging system for ALL. Chromosomes are often analyzed to determine which mutations in the chromosomes exist. The effectiveness of the treatment may depend upon the specific chromosome mutations that are present.

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 your therapy.

What does it mean to "hyperfractionate" chemo?

This is a strategy used to split up one large daily dose of chemotherapy into multiple smaller doses. This is done to expose more cancer cells to chemotherapy over a longer period of time with the hopes of killing a greater percentage of them. Not all chemotherapy medicines can be hyperfractionated because the side effects may too severe to tolerate.

What is Acrolein?

Acrolein is a break-down product (metabolite) of cyclophosphamide. If too much acrolein builds up in the bladder, it destroys the cells lining the bladder and can cause blood to appear in the urine. Mesna helps lessen the risk of this side effect by binding to and neutralizing acrolein.

What is the Philadelphia Chromosome (Ph+)?

If this is present, another medication such as imatinib (Gleevec®), nilotinib (Tasigna®), dasatinib (Sprycel®), will also be given. These medications are commonly used to treat another form of leukemia called Chronic Myeloid Leukemia (CML). The side effects are similar to those seen when used to treat ALL. These medications can either be taken continuously throughout therapy or intermittently during Part A of HyperCVAD.

Clinical Trial Results

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

1. Kantarjian HM, O'Brien S, Smith TL, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult lymphocytic leukemia. J Clin Oncol. 2000;18:547-561.

2. Kantarjian H, Thomas D, O'Brien S, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004;101:2788-2801.

3. Thomas DA, Faderl S, O'Brien S, et al. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006;106:1569-1580.

What is Tumor Lysis Syndrome?

Tumor lysis syndrome occurs when many cancer cells die quickly and release their contents into the bloodstream. Many times the body has the ability to flush these substances out through the kidneys or metabolize them via the liver. However, sometimes the body needs medicines to help eliminate these substances and to prevent organ damage.

Common Starting Doses

  • Cyclophosphamide 300 mg/m2 intravenous (I.V.) infusion, usually given over 3 hours, every 12 hours (twice daily) on days 1,2,3 (six doses total)
  • Mesna 600 mg/m2 I.V. infusion, usually given over 24 hours on days 1,2,3, ending on day 4
  • Vincristine 2 mg I.V. infusion, usually given over 15 minutes on days 4 and 11
  • Doxorubicin 50 mg/m2 I.V. infusion, given over 2 - 24 hours (infusion time depends upon hospital guidelines) on day 4
  • Dexamethasone 40 mg (ten x 4 mg) oral tablet by mouth on days 1,2,3,4 and 11,12,13, 14

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 neutropenia?

This occurs when there is an abnormally low amount of a certain type of white blood cells, called neutrophils, in the blood. These neutrophils help the body body fight infections caused by bacteria and viruses. Many chemotherapy drugs temporarily damage bone marrow where white blood cells are created, resulting in neutropenia. Please watch our video on neutropenia to learn more.

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