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Treatment Name: Dose-Dense MVAC (DD-Metho­trexate + Vinblas­tine + Adria­mycin + Cisplatin)

Dose-Dense MVAC (DD-Metho­trexate + Vinblas­tine + Adria­mycin + Cisplatin) is a Chemotherapy Regimen for Bladder Cancer

How does DD-MVAC work?
Each of the medications in DD-MVAC are designed to kill cancer cells.

DD – Dose Dense
M – Methotrexate
V - Vinblastine
A - Adriamycin (doxorubicin)
C - Cisplatin

Goals of therapy:
DD-MVAC is given to shrink tumors and alleviate symptoms of bladder cancer. It is commonly given with the goal of cure if there is no metastatic disease, meaning cancer has not spread outside the capsule of the bladder. If the disease is metastatic (spread to other areas of the body), DD-MVAC is not usually given with the goal of cure, but to relieve symptoms and improve quality of life.

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Schedule

  • Methotrexate intravenous push (I.V.) on Day 1
  • Vinblastine I.V. push over 5-10 minutes on Day 2
  • Doxorubicin I.V. push over 5-10 minutes on Day 2
  • Cisplatin I.V. infusion over 1 hour on Day 2

Estimated total infusion time for this treatment:

  • As short as 1 hour on Day 1; from 3 to 5 hours on Day 2
  • Day 2 infusion time is extended when I.V. magnesium and potassium have to be infused, plus pre-hydration and post-hydration for cisplatin
  • Day 2 infusion of electrolytes is based on labs (blood tests) before the treatment that day
  • 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

DD-MVAC is usually given in an outpatient infusion center, allowing the person to go home afterwards. On occasion, it may be given in the hospital if someone is too sick.

DD-MVAC is repeated every 14 days. This is known as one Cycle, and may be repeated up to 4 times. If the disease is not metastatic (spread to other parts of the body) then duration of therapy may last up to 4 months, depending upon response, tolerability, and number of cycles prescribed. If the disease is metastatic, DD-MVAC is continued until it no longer works or until unacceptable side effects are seen.

Click here for common starting doses.

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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 DD-MVAC are shown here.

  • Nausea/vomiting, (77%)
  • Hair loss, (68%)
  • Low white blood cells, (41%)
  • Increased bleeding risk [low platelets], (38%)
  • Sores in mouth-mucositis, (28%)
  • Tingling or numbness in fingers and toes, (14%)
  • Neutropenic fever, (10%)
  • Kidney dysfunction—increased creatinine, (6%)

Side effect videos Side Effect Videos
Nausea and VomitingNausea and VomitingHair LossHair LossNeutropenic FeverNeutropenic FeverBleedingBleedingPainPain

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Monitoring

How often is monitoring needed?
Labs (blood tests) may be checked before each treatment. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), blood magnesium levels, blood potassium levels, plus any others your doctor may order.

How often is imaging needed?
Imaging is checked before treatment, then periodically during treatment to make sure the therapy is working. Imaging may include: magnetic resonance imaging (MRI), bone scans, X-rays, or computerized tomography (CT) scans.

How might blood test results/imaging affect treatment?
Depending upon the results, your doctor may advise to continue DD-MVAC as planned, or delay or switch therapy.

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ChemoExperts Tips

  • Intravenous (I.V.) fluids may be given while receiving cisplatin to maintain good hydration and protect against kidney damage. These fluids often contain electrolytes such as potassium and magnesium and can add extra time spent in the infusion center
  • Typically, filgrastim (Neupogen®) or PEG-filgrastim (Neulasta®) is given after chemotherapy to stimulate production of white blood cells—this helps avoid periods of neutropenia (a low count of a certain type of white blood cells), and prevent infection
  • A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
  • Clinical trials may exist for bladder cancer. 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 Dose-Dense MVAC (DD-Metho­trexate + Vinblas­tine + Adria­mycin + Cisplatin), 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 Dose-Dense MVAC (DD-Metho­trexate + Vinblas­tine + Adria­mycin + Cisplatin). Depending upon your income, they may be able to help cover the cost of:

  • Methotrexate
  • Vinblastine
  • Adriamycin®
  • Cisplatin

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 Dose-Dense MVAC (DD-Metho­trexate + Vinblas­tine + Adria­mycin + Cisplatin) 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 Dose-Dense MVAC (DD-Metho­trexate + Vinblas­tine + Adria­mycin + Cisplatin)

Individual Drug Label Information

Methotrexate (Trexall®)

  • Methotrexate is an intravenous infusion and is bright yellow in color 
  • Methotrexate has the following FDA Black-Box Warnings. The risk of experiencing these side effects is much higher if methotrexate is not cleared from the body appropriately:  
    1. Low red blood cells, white blood cells, and platelets
    2. Kidney injury
    3. Liver injury
    4. Severe diarrhea
    5. Mouth ulcers
    6. Stomach ulcers
  • Dosage adjustments may be required for poor kidney function or poor liver function 
  • May cause severe skin reactions a few days after administration 
  • Is harmful to the fetus during pregnancy. If you are of childbearing age, use multiple forms of birth control 
  • May interact with non-steroidal inflammatory drugs (NSAIDs), aspirin, proton-pump inhibitors, phenytoin, and sulfa or penicillin antibiotics. These drugs should NOT be used the day before or the day of therapy with methotrexate. 
  • Ask your doctor or pharmacist to review your medications prior to receiving methotrexate 
  • Click on the methotrexate package insert below for reported side effects and possible drug interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaHair LossHair LossFatigue Fatigue PainPainAnemiaAnemiaNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Vinblastine

  • ​Vinblastine MUST only be given by intravenous infusion (by vein) usually over 1 to 5 minutes. May NOT be administered any other way. Vinblastine will cause death if administered into spinal fluid (intrathecal)
  • Dosage adjustments may be required for patients with liver problems
  • May interact with other medications you are taking, such as antifungal medicines. Ask your doctor or pharmacist to review them
General Vinblastine 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
  • Low white blood cell count; this may temporarily increase your risk for infection
  • Patients should immediately report and symptoms of fever, chills, sore throat or mouth to their doctor
  • Constipation; the use of fiber supplements or laxatives may be useful to prevent or treat constipation during this treatment.
  • Hair loss
  • Leakage into skin or surrounding muscle may cause severe irritation (extravasation)
  • Click on the vinblastine package insert below for reported side effects and possible drug interactions

Side Effect Videos
Hair LossHair LossConstipationConstipationPainPainNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Adriamycin® (Doxorubicin)

  • 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 below for reported side effects and possible drug interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaHair LossHair LossFatigue Fatigue PainPainAnemiaAnemiaNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Cisplatin (Platinol®)

  • Cisplatin is an intravenous (I.V.) infusion that is typically given over one to two hours
  • Cumulative toxicity to kidneys from cisplatin can be severe 
  • Other toxicities from multiple doses are:  low blood counts, nausea, vomiting, and hearing loss
  • Dosage adjustments may be required for poor kidney function or bone marrow toxicity (low blood counts) 
  • Cisplatin is hazardous to a human fetus; women should avoid pregnancy while on this drug 
  • Women should not breast-feed while on cisplatin; it has been reported to be in human milk 
  • Patients on anticonvulsant drugs may have decreased levels while on cisplatin 
General Cisplatin (Platinol) Side Effects 
  • Kidney problems (nephrotoxicity), especially in elderly patients. 
  • Nausea and vomiting, both acute (within first 24 hours) and delayed (two to five days after infusion) 
  • Diarrhea 
  • Low blood cell counts (myelotoxicity, acute leukemia)
  • Hearing problems- ringing ears.  All patients should have a baseline hearing test done.  All children should have hearing test done before each dose and for several years after therapy is complete 
  • Low blood electrolytes:  magnesium, potassium, calcium, sodium, and phosphate
  • Nerve pain 
  • Vision problems; improvement and/or complete recovery usually occurs after stopping therapy 
  • Liver toxicity; recovery usually occurs after stopping therapy 
  • Click on the cisplatin (Platinol) package insert below for reported side effects and possible drug interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaFatigue Fatigue PainPainAnemiaAnemiaNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

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References

1. Sternberg CN, de Mulder P, Schornagel JH, et al. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. European Journal of Cancer 2006;42(1):50-54.

2. Sternberg CN, de Mulder P, Schornage JH, et al. Randomized Phase III Trial of High–Dose-Intensity Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (MVAC) Chemotherapy and Recombinant Human Granulocyte Colony-Stimulating Factor Versus Classic MVAC in Advanced Urothelial Tract Tumors: European Organization for Research and Treatment of Cancer Protocol No. 30924. J Clin Oncol 2001;19;2638-2646

Created: December 17, 2015 Updated: September 22, 2018

What is Bladder Cancer?

A disease of the cells that line the inside of the bladder. Bladder cancer is a rare disease that is most commonly seen in older adults. It is known to cause blood in the urine in up to 90% of patients at diagnosis. Causes of bladder cancer include smoking, exposure to certain chemicals (arylamines), and chronic bladder infections.

Treatment includes surgery (full or partial removal of the bladder), chemotherapy, immunotherapy (giving certain vaccines into the bladder), or thermotherapy (heating the lining of the bladder combined with chemotherapy). The stage of bladder cancer can vary at diagnosis and throughout treatment. Bladder cancer is staged using the Tumor, Node, Metastasis (TNM) system, as well as Stage Grouping 0, I, II, III, or IV. Staging systems describe the extent of cancer throughout the body and help doctors determine which treatments to offer. 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. Sternberg CN, de Mulder P, Schornagel JH, et al. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. European Journal of Cancer 2006;42(1):50-54.

2. Sternberg CN, de Mulder P, Schornage JH, et al. Randomized Phase III Trial of High–Dose-Intensity Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (MVAC) Chemotherapy and Recombinant Human Granulocyte Colony-Stimulating Factor Versus Classic MVAC in Advanced Urothelial Tract Tumors: European Organization for Research and Treatment of Cancer Protocol No. 30924. J Clin Oncol 2001;19;2638-2646

Common Starting Doses

  • Methotrexate 30 mg/m2 IV push on Day 1
  • Vinblastine 3 mg/m2 IV push over 5-10 minutes on Day 2
  • Doxorubicin 30 mg/m2 IV push over 5-10 minutes on Day 2
  • Cisplatin 70 mg/m2 IV infusion over 1 hour on Day 2
  • G-CSF (filgrastim) or PEG-filgrastim, starting 24 hours post-chemo

Cycle is 14 Days

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.