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Home > LYM NHL B-cell PCNSL - MATRix [metHOTREXATe, cytarabine, thiotepa and RITUximab] Induction

LYM NHL B-cell PCNSL - MATRix [metHOTREXATe, cytarabine, thiotepa and RITUximab] Induction

Treatment Overview

This is an intensive protocol. It is designed to be given as an Induction therapy which would be followed by Consolidation therapy, and with either high dose therapy and autologous stem cell transplant or whole brain radiation therapy.


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).

Intrathecal therapy 

  • Required if CSF cytology/flow positive at diagnosis and after 2 cycles of Induction.
  • 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.

Cycle 1 - 21 days

Cycle length:
21

RITUximab, first dose:

  • Cycle 1 day minus 5 – treatment should not be delayed if clinical condition requires high-dose methotrexate be urgently started.
  • Consider withholding routine anti-hypertensives for 12 hours prior to first RITUximab dose.
  • For patients at high risk of infusion-related reaction, consider additional pre-medications such as an extra antihistamine dose the day before, an H2 receptor antagonist and montelukast.

RITUximab, subsequent doses:

  • Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.

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).
  • 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.

cytarabine: Renal function should be checked post high dose metHOTREXATe in the morning prior to cytarabine. If there has been a reduction in renal function from baseline the cytarabine dose should be withheld and reviewed by the haematologist.

Cycle 2 - 21 days - Followed by stem cell harvest

Cycle length:
21

RITUximab: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.


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).
  • 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.

cytarabine: Renal function should be checked post high dose metHOTREXATe in the morning prior to cytarabine. If there has been a reduction in renal function from baseline the cytarabine dose should be withheld and reviewed by the haematologist.


filgrastim: Give filgrastim 10 micrograms/kg subcutaneously ONCE daily from Day 6 until stem cell harvest.

Cycles 3 to 4 - 21 days

Cycle length:
21

RITUximab: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.


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).
  • 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.

cytarabine: Renal function should be checked post high dose metHOTREXATe in the morning prior to cytarabine. If there has been a reduction in renal function from baseline the cytarabine dose should be withheld and reviewed by the haematologist.

Cycle details

Cycle 1 - 21 days

Medication Dose Route Days Max Duration
paracetamol * 1000 mg flat dosing oral administration -5, 0
loratadine * 10 mg oral administration -5, 0
dexamethasone * 12 mg flat dosing intravenous -5 15 minutes
RITUximab 375 mg/m² intravenous -5, 0 6 hours
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 * 500 mg/m² intravenous 1 15 minutes
metHOTREXATe * 3000 mg/m² intravenous 1 3 hours
foliNIc acid (as calcium folinate) 30 mg flat dosing Every six hours intravenous 2, 3, 4 2 minutes
cytarabine * 2000 mg/m² Twice daily intravenous 2, 3 60 minutes
prednisolone acetate 1% (10 mg/mL) eye drops * 1 Drop Every four hours application to the eye 2 to 5
thiotepa 30 mg/m² intravenous 4 30 minutes
pegFILGRASTIM 6 mg subcutaneous injection 6

RITUximab, first dose:

  • Cycle 1 day minus 5 – treatment should not be delayed if clinical condition requires high-dose methotrexate be urgently started.
  • Consider withholding routine anti-hypertensives for 12 hours prior to first RITUximab dose.
  • For patients at high risk of infusion-related reaction, consider additional pre-medications such as an extra antihistamine dose the day before, an H2 receptor antagonist and montelukast.

RITUximab, subsequent doses:

  • Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.

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).
  • 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.

cytarabine: Renal function should be checked post high dose metHOTREXATe in the morning prior to cytarabine. If there has been a reduction in renal function from baseline the cytarabine dose should be withheld and reviewed by the haematologist.

Cycle 2 - 21 days - Followed by stem cell harvest

Medication Dose Route Days Max Duration
paracetamol * 1000 mg flat dosing oral administration -5, 0
loratadine * 10 mg oral administration -5, 0
RITUximab 375 mg/m² intravenous -5, 0 6 hours
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 * 500 mg/m² intravenous 1 15 minutes
metHOTREXATe * 3000 mg/m² intravenous 1 3 hours
foliNIc acid (as calcium folinate) * 30 mg flat dosing Every six hours intravenous 2, 3, 4 2 minutes
cytarabine * 2000 mg/m² Twice daily intravenous 2, 3 60 minutes
prednisolone acetate 1% (10 mg/mL) eye drops * 1 Drop Every four hours application to the eye 2 to 5
thiotepa 30 mg/m² intravenous 4 30 minutes
filgrastim 10 microgram/kg subcutaneous injection 6

RITUximab: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.


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).
  • 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.

cytarabine: Renal function should be checked post high dose metHOTREXATe in the morning prior to cytarabine. If there has been a reduction in renal function from baseline the cytarabine dose should be withheld and reviewed by the haematologist.


filgrastim: Give filgrastim 10 micrograms/kg subcutaneously ONCE daily from Day 6 until stem cell harvest.

Cycles 3 to 4 - 21 days

Medication Dose Route Days Max Duration
paracetamol * 1000 mg flat dosing oral administration -5, 0
loratadine * 10 mg oral administration -5, 0
RITUximab 375 mg/m² intravenous -5, 0 6 hours
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 * 500 mg/m² intravenous 1 15 minutes
metHOTREXATe * 3000 mg/m² intravenous 1 3 hours
foliNIc acid (as calcium folinate) * 30 mg flat dosing Every six hours intravenous 2, 3, 4 2 minutes
cytarabine * 2000 mg/m² Twice daily intravenous 2, 3 60 minutes
prednisolone acetate 1% (10 mg/mL) eye drops * 1 Drop Every four hours application to the eye 2 to 5
thiotepa 30 mg/m² intravenous 4 30 minutes
pegFILGRASTIM 6 mg subcutaneous injection 6

RITUximab: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.


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).
  • 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.

cytarabine: Renal function should be checked post high dose metHOTREXATe in the morning prior to cytarabine. If there has been a reduction in renal function from baseline the cytarabine dose should be withheld and reviewed by the haematologist.

Full details

Cycle 1 - 21 days

Day: -5

Medication Dose Route Max duration Details
paracetamol * 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
dexamethasone * 12 mg flat dosing intravenous 15 minutes
Instructions:

30 to 60 minutes prior to RITUximab.
RITUximab 375 mg/m² intravenous 6 hours
Instructions:
  • Consider withholding routine anti-hypertensives for 12 hours prior to first RITUximab dose.
  • For patients at high risk of infusion-related reaction, consider additional pre-medications such as an extra antihistamine dose the day before, an H2 receptor antagonist and montelukast.
  • Start infusion at 50 mg/hour. If tolerated, rate can be increased by 50 mg/hour every 30 minutes to a maximum rate of 400 mg/hour.

Day: 0

Medication Dose Route Max duration Details
paracetamol * 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
RITUximab 375 mg/m² intravenous 6 hours
Instructions:
  • Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated as per institutional practice.
  • Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour, or as per institutional practice.

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 * 500 mg/m² intravenous 15 minutes
metHOTREXATe * 3000 mg/m² intravenous 3 hours
Instructions:

Starting immediately after the 15 minute metHOTREXATe infusion.

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.
cytarabine * 2000 mg/m² Twice daily intravenous 60 minutes
Instructions:

Every 12 hours.

If renal function reduced from baseline following high dose metHOTREXATe, dose should be withheld and reviewed by the haematologist.
prednisolone acetate 1% (10 mg/mL) eye drops * 1 Drop Every four hours application to the eye
Instructions:

Instil ONE drop into each eye every FOUR hours on days 2 to 5.

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.
cytarabine * 2000 mg/m² Twice daily intravenous 60 minutes
Instructions:

Every 12 hours.
prednisolone acetate 1% (10 mg/mL) eye drops * 1 Drop Every four hours application to the eye
Instructions:

Instil ONE drop into each eye every FOUR hours on days 2 to 5.

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.
prednisolone acetate 1% (10 mg/mL) eye drops * 1 Drop Every four hours application to the eye
Instructions:

Instil ONE drop into each eye every FOUR hours on days 2 to 5.
thiotepa 30 mg/m² intravenous 30 minutes
Instructions:

Administer via an in-line filter of 0.2 microns size.

Day: 5

Medication Dose Route Max duration Details
prednisolone acetate 1% (10 mg/mL) eye drops * 1 Drop Every four hours application to the eye
Instructions:

Instil ONE drop into each eye every FOUR hours on days 2 to 5.

Day: 6

Medication Dose Route Max duration Details
pegFILGRASTIM 6 mg subcutaneous injection

Cycle 2 - 21 days - Followed by stem cell harvest

Day: -5

Medication Dose Route Max duration Details
paracetamol * 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
RITUximab 375 mg/m² intravenous 6 hours
Instructions:
  • Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated as per institutional practice.
  • Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour.

Day: 0

Medication Dose Route Max duration Details
paracetamol * 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
RITUximab 375 mg/m² intravenous 6 hours
Instructions:
  • Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated as per institutional practice.
  • Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour, or as per institutional practice.

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 * 500 mg/m² intravenous 15 minutes
metHOTREXATe * 3000 mg/m² intravenous 3 hours
Instructions:

Starting immediately after the 15 minute metHOTREXATe infusion.

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.
cytarabine * 2000 mg/m² Twice daily intravenous 60 minutes
Instructions:

Every 12 hours.

If renal function reduced from baseline following high dose metHOTREXATe, dose should be withheld and reviewed by the haematologist.
prednisolone acetate 1% (10 mg/mL) eye drops * 1 Drop Every four hours application to the eye
Instructions:

Instil ONE drop into each eye every FOUR hours on days 2 to 5.

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.
cytarabine * 2000 mg/m² Twice daily intravenous 60 minutes
Instructions:

Every 12 hours.
prednisolone acetate 1% (10 mg/mL) eye drops * 1 Drop Every four hours application to the eye
Instructions:

Instil ONE drop into each eye every FOUR hours on days 2 to 5.

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.
prednisolone acetate 1% (10 mg/mL) eye drops * 1 Drop Every four hours application to the eye
Instructions:

Instil ONE drop into each eye every FOUR hours on days 2 to 5.
thiotepa 30 mg/m² intravenous 30 minutes
Instructions:

Administer via an in-line filter of 0.2 microns size.

Day: 5

Medication Dose Route Max duration Details
prednisolone acetate 1% (10 mg/mL) eye drops * 1 Drop Every four hours application to the eye
Instructions:

Instil ONE drop into each eye every FOUR hours on days 2 to 5.

Day: 6

Medication Dose Route Max duration Details
filgrastim 10 microgram/kg subcutaneous injection
Instructions:

Give ONCE daily from Day 6 until stem cell harvest.

Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Cycles 3 to 4 - 21 days

Day: -5

Medication Dose Route Max duration Details
paracetamol * 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
RITUximab 375 mg/m² intravenous 6 hours
Instructions:
  • Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated as per institutional practice.
  • Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour.

Day: 0

Medication Dose Route Max duration Details
paracetamol * 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
RITUximab 375 mg/m² intravenous 6 hours
Instructions:
  • Consider administering corticosteroid premedication if previous doses not well tolerated or if clinically indicated as per institutional practice.
  • Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour, or as per institutional practice.

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 * 500 mg/m² intravenous 15 minutes
metHOTREXATe * 3000 mg/m² intravenous 3 hours
Instructions:

Starting immediately after the 15 minute metHOTREXATe infusion.

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.
cytarabine * 2000 mg/m² Twice daily intravenous 60 minutes
Instructions:

Every 12 hours.

If renal function reduced from baseline following high dose metHOTREXATe, dose should be withheld and reviewed by the haematologist.
prednisolone acetate 1% (10 mg/mL) eye drops * 1 Drop Every four hours application to the eye
Instructions:

Instil ONE drop into each eye every FOUR hours on days 2 to 5.

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.
cytarabine * 2000 mg/m² Twice daily intravenous 60 minutes
Instructions:

Every 12 hours.
prednisolone acetate 1% (10 mg/mL) eye drops * 1 Drop Every four hours application to the eye
Instructions:

Instil ONE drop into each eye every FOUR hours on days 2 to 5.

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.
prednisolone acetate 1% (10 mg/mL) eye drops * 1 Drop Every four hours application to the eye
Instructions:

Instil ONE drop into each eye every FOUR hours on days 2 to 5.
thiotepa 30 mg/m² intravenous 30 minutes
Instructions:

Administer via an in-line filter of 0.2 microns size.

Day: 5

Medication Dose Route Max duration Details
prednisolone acetate 1% (10 mg/mL) eye drops * 1 Drop Every four hours application to the eye
Instructions:

Instil ONE drop into each eye every FOUR hours on days 2 to 5.

Day: 6

Medication Dose Route Max duration Details
pegFILGRASTIM 6 mg subcutaneous injection

Supportive Care Factors

Factor Value
Antiviral prophylaxis for hepatitis B virus: Required for anti–HBc positive patients at risk of reactivation
Antiviral prophylaxis for herpes virus: Routine antiviral prophylaxis recommended
Emetogenicity: Variable
Folinic acid rescue for high dose methotrexate: Mandatory
Growth factor support: Recommended for primary prophylaxis
Hydration: Routine hydration recommended
Hypersensitivity / Infusion related reaction risk: High - routine premedication recommended
Ocular toxicity risk: High - administer corticosteroid eyedrops to minimise corneal toxicity
Pneumocystis jirovecii pneumonia (PJP) prophylaxis: Routine antibiotic prophylaxis recommended
Tumour lysis syndrome prophylaxis: Tumour lysis syndrome prophylaxis is recommended

Emetogenicity:

  • MINIMAL day minus 5 and day 0.
  • MEDIUM day 1, high dose metHOTREXATe may be highly emetogenic in certain patients.
  • MEDIUM days 2 and 3.
  • LOW day 4.

PJP prophylaxis: If trimethoprim + sulfamethoxazole is used as prophylaxis, it is recommended to withhold at least 48 hours prior to high dose metHOTREXATe administration and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (as per institutional practice).


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

References

Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosée PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Rudà R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gørløv JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group (IELSG). Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and Rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016 May;3(5):e217-27. doi: 10.1016/S2352-3026(16)00036-3. Epub 2016 Apr 6., PMID: 27132696

Adienne SA FDA prescribing information Tepadina 1/2017 https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208264s000lbl.pdf (accessed 26 May 2022)

Tabernero J, Vyas M, Giuliani R, Arnold D, Cardoso F, Casali PG, Cervantes A, Eggermont AMM, Eniu A, Jassem J, Pentheroudakis G, Peters S, Rauh S, Zielinski CC, Stahel RA, Voest E, Douillard JY, McGregor K, Ciardiello F. Biosimilars: a position paper of the European Society for Medical Oncology, with particular reference to oncology prescribers. ESMO Open. 2017 Jan 16;1(6):e000142. doi: 10.1136/esmoopen-2016-000142., PMID: 28848668

Lyman GH, Balaban E, Diaz M, Ferris A, Tsao A, Voest E, Zon R, Francisco M, Green S, Sherwood S, Harvey RD, Schilsky RL. American Society of Clinical Oncology Statement: Biosimilars in Oncology. J Clin Oncol. 2018 Apr 20;36(12):1260-1265. doi: 10.1200/JCO.2017.77.4893. Epub 2018 Feb 14., PMID: 29443651

Laudati C, Clark C, Knezevic A, Zhang Z, Barton-Burke M. Hypersensitivity Reactions: Priming Practice Change to Reduce Incidence in First-Dose Rituximab Treatment. Clin J Oncol Nurs. 2018 Aug 1;22(4):407-414. doi: 10.1188/18.CJON.407-414., PMID: 30035788

Doyle J, Raggatt M, Slavin M, McLachlan SA, Strasser SI, Sasadeusz JJ, Howell J, Hajkowicz K, Nandurkar H, Johnston A, Bak N, Thompson AJ. Hepatitis B management during immunosuppression for haematological and solid organ malignancies: an Australian consensus statement. Med J Aust. 2019 Jun;210(10):462-468. doi: 10.5694/mja2.50160. Epub 2019 May 19., PMID: 31104328

Medicines and Hepatitis B Reactivation Prescriber Update 38(1): 2-3 March 2017 https://medsafe.govt.nz/profs/PUArticles/March2017/MedicinesAndHepatitisB.htm

Rituximab and Hepatitis B Reactivation Prescriber Update 34(3):27 September 2013 https://www.medsafe.govt.nz/profs/PUArticles/Sept2013RituximabHepB.htm

* 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.