regimen-monograph

MVAC

Regimen Category

Evidence-Informed

Drugs Used

methotrexate , vinBLAStine , DOXOrubicin , CISplatin

A - Regimen Name

MVAC Regimen

Methotrexate-VinBLAStine-ADRIAMYCIN ® (DOXOrubicin)-CISplatin

Disease Site

Genitourinary - Bladder

Intent

Neoadjuvant
Adjuvant
Palliative

Regimen Category

Evidence-Informed :

Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.

Rationale and Uses

For the treatment of transitional cell carcinoma of the bladder or urothelium

B - Drug Regimen

methotrexate

(Round to nearest 2.5 mg)

30 mg /m²

Days 1, 15, 22

vinBLAStine

(Round to nearest 0.1 mg)

3 mg /m²

Days 2, 15, 22

DOXOrubicin

(Round to nearest 1 mg)

30 mg /m²

Day 2

CISplatin

(Round to nearest 1 mg)

70 mg /m²

Day 2

C - Cycle Frequency

REPEAT EVERY 28 DAYS

Until disease progression or unacceptable toxicity or 3 to 4 cycles in adjuvant/neoadjuvant settings

D - Premedication and Supportive Measures

Antiemetic Regimen:

Minimal (Days 1, 15, 22); High (Day 2)

Febrile Neutropenia Risk:

High

E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. The following recommendations are in use at some centres.

Dosage with toxicity

Worst Toxicity / Counts (x 10⁹/L) in previous cycle		Worst Toxicity/ Counts (x10⁹/L) in previous cycle	methotrexate (% previous dose)	vinBLAStine (% previous dose)		DOXOrubicin (% previous dose)		Cisplatin (% previous dose)
ANC <1.5	Or	Platelet < 100	Hold *
Febrile Neutropenia Or ANC < 0.5 for ≥ 5-7 d	Or	Thrombocytopenic bleeding Or Platelets < 25	Hold *, then 75%
ANC ≥ 1.5	And	Platelet ≥ 100	100%
Cardiotoxicity**			No change		No change		Discontinue	No change
Grade 2 neurotoxicity /ototoxicity			No change		Consider dose reduction		No change	↓ 25%
Grade 3 or 4 neurotoxicity/ototoxicity			No change		Discontinue		No change	Discontinue
Grade 3 related organ / non-hematologic			*75% for suspect drug(s)
Grade 4 related organ / non-hematologic Leucoencephalopathy, hepatic fibrosis, viral reactivation Hemolysis, optic neuritis, arterial thromboembolism, severe hypersensitivity reactions			Discontinue
Suspected Pneumonitis			Hold, investigate appropriately and discontinue if confirmed

_{*Do not start new cycle until toxicities have recovered to ≤ grade 2 (grade 1 for neurotoxicity), platelets ≥ 100 x 10⁹/L, and ANC ≥ 1.5 x 10⁹/L.}

_{**including any signs and symptoms of heart failure, greater than 10% decline in LVEF to below the lower limit of normal, a greater than 20% decline in LVEF from any level, or LVEF ≤ 45%.}

Hepatic Impairment

Bilirubin		AST/ALT	methotrexate (% previous dose)	vinBLAStine (% previous dose)	DOXOrubicin (% previous dose)	Cisplatin (% previous dose)
1-2 x ULN			Caution	50%	50%	No adjustment required
>2-4 x ULN	OR	2-4 x ULN	75%	25%	25%
>4 x ULN	OR	>4 x ULN	Discontinue	Discontinue	Discontinue

Renal Impairment

Creatinine clearance (mL/min)	Methotrexate (% usual dose)	Cisplatin (% previous dose)	Vinblastine and Doxorubicin
80	75%	100%	No change
60	60%*	75%
50	50%*	75%
30-50	Discontinue	50%
<30	Discontinue	Discontinue
* Less conservative dose modifications could be considered for low dose regimens (<50mg/m²)

F - Adverse Effects

Refer to methotrexate, vinBLAStine, DOXOrubicin, CISplatin drug monograph(s) for additional details of adverse effects

Most Common Side Effects	Less Common Side Effects, but may be Severe or Life-Threatening
Mucositis Diarrhea Myelosuppression ± infection, bleeding (may be severe) Nausea, vomiting Rash (may be severe) ↑ LFTs (may be severe) Alopecia Nephrotoxicity (may be severe) Electrolyte abnormalities Neurotoxicity and ototoxicity (may be severe)	Arterial/venous thromboembolism Hypersensitivity GI perforation Pancreatitis Secondary malignancies Cardiotoxicity Vesicant SIADH Photosensitivity Pneumonitis Arrhythmia Hemolytic uremic-syndrome, vasculitis Raynaud's Hemolysis

G - Interactions

Refer to methotrexate, vinBLAStine, DOXOrubicin, CISplatin drug monograph(s) for additional details

H - Drug Administration and Special Precautions

Refer to methotrexate, vinBLAStine, DOXOrubicin, CISplatin drug monograph(s) for additional details

I - Recommended Clinical Monitoring

Recommended Clinical Monitoring

CBC; baseline and regular
Electrolytes, including magnesium, phosphate and calcium; baseline and regular
Liver function tests; baseline and regular
Renal function tests; baseline and regular
Clinical toxicity assessment (infection, bleeding, nausea/vomiting, mucositis, neurotoxicity, cardiotoxicity, ototoxicity, local toxicity, pulmonary, skin, CNS); at each visit
Cardiac function tests (Echo, RNA and/or MUGA scans) for all patients with cardiac risk factors; baseline
Cardiac tests for all patients with cardiac risk factors (including prior trastuzumab or patients at or above the threshold doxorubicin cumulative dose levels (400mg/m² for q21 day schedules and 550mg/m² for weekly schedules); periodic
Audiogram; as clinically indicated
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

J - Administrative Information

Approximate Patient Visit

Day 1, 15, 22: 0.5 hour; Day 2: 4 hours

Pharmacy Workload (average time per visit)

25.086 minutes

Nursing Workload (average time per visit)

47.917 minutes

K - References

Lehmann J, Franzaring L, Thüroff J, et al. Complete long-term survival data from a trial of adjuvant chemotherapy vs control after radical cystectomy for locally advanced bladder cancer. BJU Int 2006;97(1):42-7.

Loehrer PJ Sr, Einhorn LH, Elson PJ, et al. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol, 1992;10:1066-73.

Logothetis CJ, Dexeus FH, Finn L et al. A prospective randomized trial comparing M-VAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol, 1990;8:1050-5.

Roberts JT, von der Maase H, Sengeløv L, et al. Long-term survival results of a randomized trial comparing gemcitabine/cisplatin and methotrexate/vinblastine/doxorubicin/cisplatin in patients with locally advanced and metastatic bladder cancer. Ann Oncol 2006;17 Suppl 5:v118-22.

Sternberg CN, de Mulder PH, Schornagel 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(10):2638-46.

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. Eur J Cancer. 2006;42(1):50-4.

von der Maase H, Sengelov L, Roberts JT, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 2005;23(21):4602-8.

von de Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, Phase III Study. J Clin Oncol 2000;18(17):3068-77.

October 2017 Replaced regimen category with evidence-informed

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Last Updated: July 27, 2026

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