| Cycle length: 14 days. |
| 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. | Day 1 |
| Vinblastine | 3 mg/m2 IV | Administer IV push over one minute. | Day 2 |
| Doxorubicin | 30 mg/m2 IV | Dilute in 50 mL NS* and administer over three to five minutes IV push through a peripheral line. | Day 2 |
| Cisplatin | 70 mg/m2 IV | Dilute in 250 mL NS* and administer over 60 minutes. Do not administer with aluminum needles or sets. | Day 2 |
| Pretreatment considerations: |
| Emesis risk | - HIGH.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Vesicant/irritant properties | - 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.
|
| Infection prophylaxis | - HIGH. Primary prophylaxis with G-CSF is indicated (estimated risk of febrile neutropenia >20%). All cycles should be administered with myeloid growth factor support.
- In the original protocol, G-CSF was administered during each cycle at 240 mcg/m2 SC daily on days 4 through 10 and was extended as needed up to a total of 14 consecutive days[1]. Other options include pegylated G-CSF (pegfilgrastim) 6 mg SC, or other biosimilars, administered each cycle between 24 hours[2] to 72 hours after cessation of chemotherapy.
- 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.
|
| Dose adjustment for baseline liver or renal dysfunction, and third-space fluid collections | - A lower starting dose of methotrexate may be needed for patients with liver or renal 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 doses may be needed for preexisting liver dysfunction.[5,6] Adjustment of cisplatin doses may be needed for preexisting renal dysfunction.[7]
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with kidney impairment, Cconventional 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.
|
| Hydration | - Due to the potential for nephrotoxicity associated with cisplatin, pretreatment hydration with 1 to 2 L 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.[7]
- Refer to UpToDate topics on cisplatin nephrotoxicity.
|
| 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.
|
| Monitoring parameters: |
- Obtain CBC with differential and platelet count prior to each cycle.
|
- Assess electrolytes and liver and renal function prior to each cycle. Continue close monitoring of renal function after each cycle in high-risk patients.
|
- Assess changes in neurologic function prior to each cycle.
|
- Evaluate for third-space fluid collections as clinically indicated.
|
- Assess LVEF prior to treatment initiation and as clinically indicated during therapy.
|
- Monitor for hearing loss prior to each dose of cisplatin; audiometry as clinically indicated.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Hold all chemotherapy until platelets are >90,000/mm3 and WBC is >3000/mm3.[7]
|
| Neurologic toxicity | - Neuropathy usually is seen with cumulative doses of cisplatin >400 mg/m2, although there is marked interindividual variation. Patients with mild neuropathy can continue to receive full doses of cisplatin; however, if symptoms increase in severity or the neuropathy interferes with function, the risk of potentially disabling neurotoxicity must be weighed against the benefit of continued treatment.
- 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.
|
| Cardiotoxicity | - Monitor cumulative doxorubicin dose. Reassess LVEF periodically during dose-dense MVAC therapy as clinically indicated. Discontinue doxorubicin in patients who develop signs/symptoms of cardiomyopathy.[5]
- Refer to UpToDate topics on clinical manifestations, monitoring, and diagnosis of anthracycline-induced cardiotoxicity and prevention and management of anthracycline cardiotoxicity.
|
| Renal dysfunction | - Hold cisplatin until serum creatinine <1.5 mg/dL or CrCl >55 mL/min and/or BUN <25 mg/dL.[7]
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
