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Systemic Anti-Cancer Therapy Regimen Library

Home > LYM NHL B-cell PCNSL - high dose metHOTREXATe 8 g/m2

LYM NHL B-cell PCNSL - high dose metHOTREXATe 8 g/m2

Treatment Overview

Usually 6 to 8 cycles.

  • 4 cycles of Induction.
  • 2 further cycles if complete response achieved OR 4 further cycles if partial response achieved.

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, the 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).

Intrathecal therapy 

  • Required if CSF cytology/flow positive at diagnosis and after 2 cycles.  
  • See LYM NHL B-cell - Intrathecal Triple Therapy [metHOTREXATe, cytarabine and hydrocortisone].

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 8 - 14 days

Cycle length:
14

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).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 micrograms/kg subcutaneously ONCE daily from Day 4 or when serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice), continue until neutrophil count is greater than 1 x 109/L.

Cycle details

Cycles 1 to 8 - 14 days

Medication Dose Route Days Max Duration
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% 125 mL/m²/hour intravenous 1 to 4
sodium bicarbonate 50 mmol intravenous 1 to 4
acetazolamide * 250 mg Four times daily oral administration 1 to 4
metHOTREXATe * 8000 mg/m² intravenous 1 4 hours
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2, 3, 4 2 minutes
filgrastim 5 microgram/kg Once daily subcutaneous injection 4

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).
  • Some centres can consider using an alternative dosing strategy for certain patients commencing 24 hours after the start of the metHOTREXATe infusion as foliNIc acid 300 mg IV over 24 hours before switching to 30 mg IV q6h dosing.

filgrastim: Give filgrastim 5 micrograms/kg subcutaneously ONCE daily from Day 4 or when serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice), continue until neutrophil count is greater than 1 x 109/L.

Full details

Cycles 1 to 8 - 14 days

Day: 1

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.
  • 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 * 8000 mg/m² intravenous 4 hours

Day: 2

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).
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: 3

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).
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: 4

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 4 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 4 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 4 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 4 if metHOTREXATe level is still elevated.
filgrastim 5 microgram/kg Once daily subcutaneous injection
Instructions:
  • Give ONCE daily until neutrophil count is greater than 1 x 109/L.
  • Commence filgrastim on Day 4 or once serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (level as per institutional practice).

Supportive Care Factors

Factor Value
Emetogenicity: Medium
Folinic acid rescue for high dose methotrexate: Mandatory
Growth factor support: Recommended for primary prophylaxis
Hydration: Routine hydration recommended
Tumour lysis syndrome prophylaxis: Tumour lysis syndrome prophylaxis is recommended

Antiviral prophylaxis for hepatitis B virus: Guidance is limited to high-risk anti-cancer medicines. Clinicians will need to assess individual patient risk for other anti-cancer medicines.


Emetogenicity: High dose metHOTREXATe may be highly emetogenic in certain patients.


Tumour lysis syndrome prophylaxis: Recommended for cycle 1 and consider for subsequent cycles.

References

Ferreri, A. J. 2011. "How I treat primary CNS lymphoma." Blood 118(3):510-522., PMID: 21613254

Batchelor, T. and J. S. Loeffler. 2006. "Primary CNS lymphoma." J Clin Oncol 24(8):1281-1288., PMID: 16525183

NCCN Clinical Practice Guidelines in Oncology - Central Nervous System Cancers - Version 1.2018.

Shah, G. D., J. Yahalom, D. D. Correa, et al. 2007. "Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma." J Clin Oncol 25(30):4730-4735., PMID: 17947720

Ramsey, L. B., F. M. Balis, M. M. O'Brien, et al. 2018. "Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance." Oncologist 23(1):52-61., PMID: 29079637

Thiel, E., A. Korfel, P. Martus, et al. 2010. "High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial." Lancet Oncol 11(11):1036-1047., PMID: 20970380

Batchelor, T., K. Carson, A. O'Neill, et al. 2003. "Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07." J Clin Oncol 21(6):1044-1049., PMID: 12637469

Ferreri, A. J., M. Reni, M. Foppoli, et al. 2009. "High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial." Lancet 374(9700):1512-1520., PMID: 19767089

* 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.