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Systemic Anti-Cancer Therapy Regimen Library

Home > GU Bladder Urothelial Neoadjuvant - ddMVAC [metHOTREXATe, DOXOrubicin, vinBLASTine and cISplatin] dose dense

GU Bladder Urothelial Neoadjuvant - ddMVAC [metHOTREXATe, DOXOrubicin, vinBLASTine and cISplatin] dose dense

Treatment Overview

Number of cycles: 3 to 6 cycles may be given pre cystectomy.


This regimen contains a medicine where one or more biosimilars may exist. Any biosimilars used have been reviewed by the regulator (Medsafe) and relevant specialists were consulted nationally. Where regulators, in consultation with relevant specialists, have agreed that there are no clinically significant differences in either safety or effectiveness between a biosimilar and originator product, these drugs may be used interchangeably.

Cycles 1 to 6 - 14 days

Cycle length:
14

An alternative schedule is all chemotherapy drugs administered on day 1.

Cycle details

Cycles 1 to 6 - 14 days

Medication Dose Route Days Max Duration
metHOTREXATe * 30 mg/m² intravenous 1 5 minutes
olanzapine * 5 mg oral administration 2 to 5
aprepitant 125 mg oral administration 2
aprepitant 80 mg oral administration 3, 4
dexamethasone * 12 mg oral administration 2
dexamethasone * 8 mg oral administration 3, 4, 5
ondansetron 8 mg oral administration 2
DOXOrubicin 30 mg/m² intravenous 2 15 minutes
vinBLASTine * 3 mg/m² intravenous 2 10 minutes
magnesium sulfate heptahydrate 10 mmol intravenous 2 60 minutes
cISplatin 70 mg/m² intravenous 2 60 minutes
sodium chloride 0.9 % intravenous 2 60 minutes
ondansetron 8 mg oral administration 2
cycliZINE 50 mg Three times daily oral administration 2
docusate sodium + sennoside B 2 Tablet(s) oral administration 2
pegFILGRASTIM 6 mg subcutaneous injection 3

An alternative schedule is all chemotherapy drugs administered on day 1.

Full details

Cycles 1 to 6 - 14 days

Day: 1

Medication Dose Route Max duration Details
metHOTREXATe * 30 mg/m² intravenous 5 minutes

Day: 2

Medication Dose Route Max duration Details
olanzapine * 5 mg oral administration
Instructions:

ONE hour prior to chemotherapy.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
  • Some centres may choose to omit pre-chemotherapy dose or advise patient to take the night before chemotherapy if patient has to drive to appointment.
aprepitant 125 mg oral administration
Instructions:
ONE hour prior to chemotherapy.
dexamethasone * 12 mg oral administration
Instructions:

ONE hour prior to chemotherapy with food.
ondansetron 8 mg oral administration
Instructions:

ONE hour prior to chemotherapy.
DOXOrubicin 30 mg/m² intravenous 15 minutes
Instructions:

Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
vinBLASTine * 3 mg/m² intravenous 10 minutes
Instructions:
  • Diluted in a minibag
  • FOR INTRAVENOUS USE ONLY – fatal if given by any other routes
  • Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
magnesium sulfate heptahydrate 10 mmol intravenous 60 minutes
Instructions:
In 1000 mL of sodium chloride 0.9%, prior to cISplatin infusion.
cISplatin 70 mg/m² intravenous 60 minutes
Instructions:
  • In 500 - 1000 mL of sodium chloride 0.9%, depending on stability.
  • Ensure patient has passed urine as per institutional policy.
  • Hypersensitivity risk increases with number of cycles of cISplatin.
sodium chloride 0.9 % intravenous 60 minutes
Quantity:1000 mL
Instructions:

After cISplatin infusion.

If cISplatin is infused in 1000 mL, centres may choose to omit this bag of fluid.
ondansetron 8 mg oral administration
Instructions:

EIGHT hours after chemotherapy OR before bed.
cycliZINE 50 mg Three times daily oral administration
Instructions:

When required for nausea and/or vomiting.

  • Warning: may cause drowsiness.
  • Consider starting dose at 25 mg and increasing as tolerated/required.
  • The choice of rescue antiemetic may be substituted to reflect institutional policy or individual patient characteristics.
  • Note that domperidone is not recommended in combination with olanzapine and ondansetron due to potential risk of QT prolongation.
docusate sodium + sennoside B 2 Tablet(s) oral administration
Instructions:

At night when required for constipation.

Each tablet contains docusate sodium 50 mg + sennoside B 8 mg.

Day: 3

Medication Dose Route Max duration Details
olanzapine * 5 mg oral administration
Instructions:

ONCE daily.

This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
aprepitant 80 mg oral administration
Instructions:
ONCE daily in the morning.
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

Dose and duration may be individualised at clinician’s discretion.
pegFILGRASTIM 6 mg subcutaneous injection

Day: 4

Medication Dose Route Max duration Details
olanzapine * 5 mg oral administration
Instructions:

ONCE daily.

This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
aprepitant 80 mg oral administration
Instructions:
ONCE daily in the morning.
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

Dose and duration may be individualised at clinician’s discretion.

Day: 5

Medication Dose Route Max duration Details
olanzapine * 5 mg oral administration
Instructions:

ONCE daily.

This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

Dose and duration may be individualised at clinician’s discretion.

Supportive Care Factors

Factor Value
Constipation risk: laxatives are usually prescribed
Emetogenicity: Variable
Growth factor support: Recommended for primary prophylaxis
Hydration: Routine hydration recommended

Emetogenicity: MINIMAL day 1, HIGH day 2.

References

Advanced Bladder Cancer Meta-analysis, Collaboration. 2005. "Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration." Eur Urol 48(2);202-5., PMID: 15939524

Blick, C., P. Hall, T. Pwint, et al. 2012. "Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant chemotherapy for patients with muscle-invasive transitional cell carcinoma of the bladder." Cancer 118(16):3920-3927., PMID: 22614698

Choueiri TK, Jacobus S, et al. Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: pathologic, radiologic, and biomarker correlates. J Clin Oncol. 2014 Jun 20;32(18):1889-94. Epub 2014 May 12. , PMID: 24821883

Grossman, H. B., R. B. Natale, C. M. Tangen, et al. 2003. "Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer." N Engl J Med 349(9):859-866., PMID: 12944571

Pfister, C., G. Gravis, A. Flechon, et al. 2022. "Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients With Nonmetastatic Muscle-Invasive Bladder Cancer: Results of the GETUG-AFU V05 VESPER Trial." J Clin Oncol 40(18):2013-2022., PMID: 35254888

Plimack ER, Hoffman-Censits JH, et al. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer: results of a multicenter phase II study with molecular correlates of response and toxicity. J Clin Oncol. 2014 Jun 20;32(18):1895-901. Epub 2014 May 12., PMID: 24821881

Sternberg, C. N., P. de Mulder, J. H. Schornagel, et al. 2006. "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 42(1):50-54., PMID: 16330205

Sternberg, C. N., P. H. de Mulder, J. H. Schornagel, et al. 2001. "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 19(10):2638-2646., PMID: 11352955

Tjokrowidjaja, A., C. Lee and M. R. Stockler. 2013. "Does chemotherapy improve survival in muscle-invasive bladder cancer (MIBC)? A systematic review and meta-analysis (MA) of randomized controlled trials (RCT)." J Clin Oncol 31 (15_Suppl): abstract 4544.

von der, Maase H., S. W. Hansen, J. T. Roberts, et al. 2000. "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. 18(17):3068-3077., PMID: 11001674

Boulanger J, Boursiquot JN, Cournoyer G, et al. Management of hypersensitivity to platinum- and taxane-based chemotherapy: cepo review and clinical recommendations. Curr Oncol. 2014;21(4):e630-e641., PMID: 25089112

Castells, M.C., Matulonis, U.A., and Horton, TM. Infusion reactions to systemic chemotherapy. Savarese DMF and Feldweg AM, ed. UpToDate. Waltham, MA: UpToDate Inc. https://wwwuptodate.com (Accessed 26 March 2021).

* The medicines, doses, combinations, and schedule in this treatment regimen have been carefully reviewed against international best practice guidelines by specialists in medical oncology around New Zealand and this advice has been accepted for publication by Te Aho o Te Kahu (the Cancer Control Agency). Sometimes medicines that are used in routine clinical practice have not been through a formal review process by the NZ Medicines Regulator Medsafe and are therefore considered unapproved or off-label. These medicines are legally able to be prescribed through sections 25 and 29 of the Medicines Act and by obtaining informed consent from patients. All treatment regimens listed on this website have been through robust peer review and are considered an accepted standard of care, whether prescribed through sections 25 or 29 or carrying formal Medsafe Approval.

s29: This symbol indicates that some formulations of the associated medicine are legally only able to be prescribed under section 29 of the Medicines Act. You can see which formulations are section 29 by hovering over the s29 symbol. You can access full medication details from the New Zealand Formulary by clicking on the medication name. Each clinician retains full responsibility for ensuring they have complied with all relevant obligations and requirements of section 29 including obtaining informed patient consent prior to prescribing the applicable medicine.