Cycle length: 28 days.
Total cycles: 6. |
| Drug | Dose and route | Administration | Given on days |
| Methotrexate | 30 mg/m2 IV | Dilute in NS* to a final concentration of 50 mg/mL, and administer as a slow IV push. | Days 1, 15, and 22 |
| Vinblastine | 3 mg/m2 IV | Administer IV push over one minute. | Days 2, 15, and 22 |
| Doxorubicin | 30 mg/m2 IV | Dilute in 50 mL NS* and administer over three to five minutes or IV push through a peripheral line. | Day 2 |
| Cisplatin | 70 mg/m2 IV | Dilute with 250 mL NS* and administer over 60 minutes. Do not administer with aluminum needles or sets. | Day 2 |
| Pretreatment considerations: |
| Emesis risk | - HIGH (>90% frequency of emesis).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Hydration | - Due to the potential for nephrotoxicity associated with cisplatin, pretreatment hydration with 1 to 2 liters of fluid is recommended prior to cisplatin administration; adequate post hydration and urinary output (>100 mL/hour) should be maintained for 24 hours after administration.[2]
- Refer to UpToDate topics on cisplatin nephrotoxicity.
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| Vesicant/irritant properties | - Both doxorubicin and vinblastine are vesicants and can cause significant tissue damage; avoid extravasation. Cisplatin is an irritant but can cause significant tissue damage; avoid extravasation.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
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| Infection prophylaxis | - This regimen was found to have an incidence of febrile neutropenia of 10% in clinical trials.[1] The decision whether or not to use hematopoietic growth factors must be individualized.
- Refer to UpToDate topics on use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation.
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| Dose adjustment for baseline liver or kidney dysfunction and third-space fluid collections | - A lower starting dose of methotrexate may be needed for patients with liver or kidney impairment, and in those with third-space fluid collections (ascites, pleural effusion, etc).[3] Methotrexate should not be administered in the setting of severe liver impairment (total bilirubin >4 × ULN).[4] A lower starting dose of vinblastine and doxorubicin may be needed for preexisting liver dysfunction.[5,6] Adjustment of cisplatin doses may be needed for preexisting kidney dysfunction.[2]
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with kidney impairment, conventional cytotoxic agents; chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents; and chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents.
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| Cardiopulmonary issues | - Doxorubicin is associated with cardiomyopathy, the incidence of which is related to cumulative dose. Assess LVEF before and regularly during and after treatment with doxorubicin.[5] Doxorubicin is contraindicated for patients with recent myocardial infarction, severe myocardial dysfunction, severe arrhythmia, or previous therapy with high cumulative doses of doxorubicin or any other anthracyclines.[5]
- Refer to UpToDate topics on clinical manifestations, monitoring, and diagnosis of anthracycline-induced cardiotoxicity and prevention and management of anthracycline cardiotoxicity.
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| Monitoring parameters: |
- CBC with differential and platelet count prior to each cycle.
|
- Assess electrolyte and liver and kidney function prior to each cycle. Continue close monitoring of kidney function after each cycle in high-risk patients.
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- Assess changes in neurologic function prior to each cycle.
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- Evaluate for third-space fluid collections as clinically indicated.
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- Assess left ventricular ejection fraction prior to treatment initiation and as clinically indicated during therapy.
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- Monitor for hearing loss prior to each dose of cisplatin; audiometry as clinically indicated.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Delay treatment cycle until the WBC count is >3000/mm3 and platelet count is >90,000 mm3.[1] Methotrexate and doxorubicin doses should be reduced by 33% in patients who have a nadir WBC <2000/mm3.[1]
|
| Neurologic toxicity | - Cisplatin therapy should be discontinued when neurologic symptoms are first observed.[2] The manufacturer recommends a dose reduction of vinblastine by 1 mg/m2 in patients with severe neurotoxicity.[6]
- Refer to UpToDate topics on overview of neurologic complications of platinum-based chemotherapy.
- For severe paresthesias and/or constipation, the dose of vinblastine should be reduced by 50%.[6] Vinblastine should be discontinued permanently if an adynamic ileus occurs.
- Refer to UpToDate topics on overview of neurologic complications of conventional non-platinum cancer chemotherapy.
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| Mucositis | - Doses of methotrexate should be reduced by 33% in patients who develop grade 3 or grade 4 mucositis.[3]
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| Cardiotoxicity | - Discontinue doxorubicin in patients who develop signs/symptoms of cardiomyopathy.[5]
- Monitor cumulative doxorubicin dose and reassess LVEF periodically during MVAC therapy as clinically indicated.
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| Kidney dysfunction | - Hold cisplatin until serum creatinine <1.5 mg/dL or CrCl >55 mL/min and/or BUN <25 mg/dL.[2]
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
