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Systemic Anti-Cancer Therapy Regimen Library

Home > SAR Osteosarcoma - MAP [metHOTREXATe, DOXOrubicin and cISplatin] > SAR - MAP [metHOTREXATe, DOXOrubicin and cISplatin]
This regimen is a component of SAR Osteosarcoma - MAP [metHOTREXATe, DOXOrubicin and cISplatin]

Part 1: MAP [metHOTREXATe, DOXOrubicin and cISplatin] (SAR Osteosarcoma - MAP [metHOTREXATe, DOXOrubicin and cISplatin])

Treatment Overview

For 4 cycles, usually administered as 2 Neoadjuvant cycles then surgery followed by 2 Adjuvant cycles. Consult protocol for details.

In patients older than 40 years, consider using cISplatin and DOXOrubicin without high dose metHOTREXATe. 


High dose metHOTREXATe:

  • metHOTREXATe levels MUST be measured once every 24 hours.
  • Intravenous alkalinized fluids MUST be commenced at least 6 hours before the start of metHOTREXATe infusion and MUST continue until the metHOTREXATe serum level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Additional oral alkalinization can be considered as Ural® 2 sachets orally the night before and 2 sachets the morning of high dose metHOTREXATe infusion.
  • Before commencing the high dose metHOTREXATe infusion, urinary pH MUST be 7.5 or above (pH 7.5 to 8.0).
  • Closely monitor renal function, electrolytes, fluid balance, and weight.
  • foliNIc acid MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).

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 4 - 35 days

Cycle length:
35

metHOTREXATe: Some centres may choose to cap the dose of metHOTREXATe at 20 000 mg.


foliNIc acid: MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).

Cycle details

Cycles 1 to 4 - 35 days

Medication Dose Route Days Max Duration
olanzapine * 5 mg oral administration 1 to 5
aprepitant 125 mg oral administration 1
aprepitant 80 mg oral administration 2, 3
dexamethasone * 12 mg oral administration 1
dexamethasone * 8 mg oral administration 2 to 5,
22, 23, 24,
29, 30, 31
ondansetron 8 mg oral administration 1, 2, 22,
29
DOXOrubicin * 37.5 mg/m² Once daily intravenous 1, 2 15 minutes
magnesium sulfate heptahydrate 10 mmol intravenous 1, 2 60 minutes
cISplatin * 60 mg/m² Once daily intravenous 1, 2 120 minutes
sodium chloride 0.9 % intravenous 1, 2 60 minutes
pegFILGRASTIM 6 mg subcutaneous injection 3
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous 22 to 25,
29 to 32
sodium bicarbonate 50 mmol intravenous 22 to 25,
29 to 32
acetazolamide * 250 mg Four times daily oral administration 22 to 25,
29 to 32
metHOTREXATe 12000 mg/m² intravenous 22, 29 4 hours
foliNIc acid (as calcium folinate) * 30 mg flat dosing Every six hours intravenous 23, 24, 25,
30, 31, 32		 2 minutes
ondansetron 8 mg oral administration 1, 2, 22,
29
cyclIZINE 50 mg Three times daily oral administration 1

metHOTREXATe: Some centres may choose to cap the dose of metHOTREXATe at 20 000 mg.


foliNIc acid: MUST start 24 hours after start of metHOTREXATe infusion and MUST continue to be administered every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).

Full details

Cycles 1 to 4 - 35 days

Day: 1

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 * 37.5 mg/m² Once daily 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.
magnesium sulfate heptahydrate 10 mmol intravenous 60 minutes
Instructions:
In 1000 mL of sodium chloride 0.9%, prior to cISplatin infusion.
cISplatin * 60 mg/m² Once daily intravenous 120 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.

Day: 2

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.
ondansetron 8 mg oral administration
Instructions:

ONE hour prior to chemotherapy.
DOXOrubicin * 37.5 mg/m² Once daily 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.
magnesium sulfate heptahydrate 10 mmol intravenous 60 minutes
Instructions:
In 1000 mL of sodium chloride 0.9%, prior to cISplatin infusion.
cISplatin * 60 mg/m² Once daily intravenous 120 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.

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.
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.

Day: 22

Medication Dose Route Max duration Details
dexamethasone * 8 mg oral administration
Instructions:

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

ONE hour prior to chemotherapy.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
metHOTREXATe 12000 mg/m² intravenous 4 hours
Instructions:

Some centres may choose to cap the dose of metHOTREXATe at 20 000 mg.
ondansetron 8 mg oral administration
Instructions:

EIGHT hours after chemotherapy OR before bed.

Day: 23

Medication Dose Route Max duration Details
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

Dose and duration may be individualised at clinician’s discretion.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) * 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 24

Medication Dose Route Max duration Details
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

Dose and duration may be individualised at clinician’s discretion.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) * 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 25

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 25 if metHOTREXATe level is still elevated.
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
  • Administration may continue past Day 25 if metHOTREXATe level is still elevated.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 25 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate) * 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
  • Administration may continue past Day 25 if metHOTREXATe level is still elevated.

Day: 29

Medication Dose Route Max duration Details
dexamethasone * 8 mg oral administration
Instructions:

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

ONE hour prior to chemotherapy.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Commence at least 6 hours prior to metHOTREXATe infusion and run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
metHOTREXATe 12000 mg/m² intravenous 4 hours
Instructions:

Some centres may choose to cap the dose of metHOTREXATe at 20 000 mg.
ondansetron 8 mg oral administration
Instructions:

EIGHT hours after chemotherapy OR before bed.

Day: 30

Medication Dose Route Max duration Details
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

Dose and duration may be individualised at clinician’s discretion.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) * 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Starting 24 hours after start of metHOTREXATe infusion and continue to administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 31

Medication Dose Route Max duration Details
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

Dose and duration may be individualised at clinician’s discretion.
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
foliNIc acid (as calcium folinate) * 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.

Day: 32

Medication Dose Route Max duration Details
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous
Instructions:
  • To each 1000 mL bag admix 50 mmol sodium bicarbonate.
  • Or an alternative alkalinized intravenous infusion may be used as per institutional practice.
  • Run continuously until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 32 if metHOTREXATe level is still elevated.
sodium bicarbonate 50 mmol intravenous
Instructions:
  • Admix 50 mmol sodium bicarbonate to each 1000 mL bag of potassium chloride 20 mmol + sodium chloride 0.18% + glucose 4%.
  • Dose of sodium bicarbonate is approximately 6 mmol/m2/hour when admixed bag is infused at 125 mL/m2/hour.
  • Administration may continue past Day 32 if metHOTREXATe level is still elevated.
acetazolamide * 250 mg Four times daily oral administration
Instructions:

When required.

  • Administer immediately if urinary pH drops below 7.5 during metHOTREXATe infusion and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • Administration may continue past Day 32 if metHOTREXATe level is still elevated.
foliNIc acid (as calcium folinate) * 30 mg flat dosing Every six hours intravenous 2 minutes
Instructions:
  • Administer every 6 hours until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
  • If metHOTREXATe elimination is impaired the dose of foliNIc acid will need to be increased. Consult prescribing information.
  • Administration may continue past Day 32 if metHOTREXATe level is still elevated.

Supportive Care Factors

Factor Value
Emetogenicity: Variable
Folinic acid rescue for high dose methotrexate: Mandatory
Growth factor support: Recommended for primary prophylaxis
Hydration: Routine hydration recommended

Emetogenicity:

  • HIGH days 1 and 2.
  • MEDIUM days 22 and 29, high dose metHOTREXATe may be highly emetogenic in certain patients.

References

No references

* 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.