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Systemic Anti-Cancer Therapy Regimen Library

Home > LYM NHL B-cell PCNSL Relapsed - R-IE [RITUximab, IFOSFamide and etoposide]

LYM NHL B-cell PCNSL Relapsed - R-IE [RITUximab, IFOSFamide and etoposide]

Treatment Overview

Usually 4 cycles. Assess patient after cycle 2; if in complete remission (CR), partial remission (PR) or has stable disease (SD) give 2 more cycles R-IE (4 cycles in total). 


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:

  • 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.

filgrastim:

  • Give 5 microgram/kg subcutaneously ONCE daily from day 4 until neutrophil recovery past the nadir, or as per institutional policy for prophylaxis.
  • If for stem cell harvest, mobilise as per institutional practice.

Cycles 2 to 4 - 21 days

Cycle length:
21

RITUximab, subsequent doses:

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

filgrastim:

  • Give 5 microgram/kg subcutaneously ONCE daily from day 4 until neutrophil recovery past the nadir, or as per institutional policy for prophylaxis.
  • If for stem cell harvest, mobilise as per institutional practice.

Cycle details

Cycle 1 - 21 days

Medication Dose Route Days Max Duration
paracetamol * 1000 mg flat dosing oral administration 0
loratadine * 10 mg oral administration 0
dexamethasone * 12 mg flat dosing intravenous 0 15 minutes
RITUximab 375 mg/m² intravenous 0 6 hours
etoposide (as phosphate) 250 mg/m² intravenous 1 60 minutes
sodium chloride 0.9 % intravenous 1, 2, 3 120 minutes
mesna 400 mg/m² intravenous 1, 2, 3 15 minutes
IFOSFamide * 2000 mg/m² Once daily intravenous 1, 2, 3 120 minutes
sodium chloride 0.9 % intravenous 1, 2, 3 120 minutes
mesna 800 mg/m² Every four hours oral administration 1, 2, 3
filgrastim 5 microgram/kg Once daily subcutaneous injection 4

RITUximab, first dose:

  • 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.

filgrastim:

  • Give 5 microgram/kg subcutaneously ONCE daily from day 4 until neutrophil recovery past the nadir, or as per institutional policy for prophylaxis.
  • If for stem cell harvest, mobilise as per institutional practice.

Cycles 2 to 4 - 21 days

Medication Dose Route Days Max Duration
paracetamol * 1000 mg flat dosing oral administration 0
loratadine * 10 mg oral administration 0
RITUximab 375 mg/m² intravenous 0 6 hours
etoposide (as phosphate) 250 mg/m² intravenous 1 60 minutes
sodium chloride 0.9 % intravenous 1, 2, 3 120 minutes
mesna 400 mg/m² intravenous 1, 2, 3 15 minutes
IFOSFamide * 2000 mg/m² Once daily intravenous 1, 2, 3 120 minutes
sodium chloride 0.9 % intravenous 1, 2, 3 120 minutes
mesna 800 mg/m² Every four hours oral administration 1, 2, 3
filgrastim 5 microgram/kg Once daily subcutaneous injection 4

RITUximab, subsequent doses:

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

filgrastim:

  • Give 5 microgram/kg subcutaneously ONCE daily from day 4 until neutrophil recovery past the nadir, or as per institutional policy for prophylaxis.
  • If for stem cell harvest, mobilise as per institutional practice.

Full details

Cycle 1 - 21 days

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.
dexamethasone * 12 mg flat dosing intravenous 15 minutes
Instructions:

30 to 60 minutes prior to RITUximab, or as per institutional practice.
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: 1

Medication Dose Route Max duration Details
etoposide (as phosphate) 250 mg/m² intravenous 60 minutes
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

Prior to IFOSFamide infusion.

Recommended daily hydration is 3000 ml per day as oral or IV fluid on day(s) of IFOSFamide and for 24 hours after, or as per institutional practice.
mesna 400 mg/m² intravenous 15 minutes
Instructions:

Immediately prior to IFOSFamide infusion over 15 minutes, or as per institutional practice.
IFOSFamide * 2000 mg/m² Once daily intravenous 120 minutes
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

After IFOSFamide infusion.

Recommended daily hydration is 3000 ml per day as oral or IV fluid on day(s) of IFOSFamide and for 24 hours after, or as per institutional practice.
mesna 800 mg/m² Every four hours oral administration
Instructions:

For 2 doses, at 2 hours and 6 hours after the start of IFOSFamide infusion, or as per institutional practice.

Round dose to closest multiple of 400 mg or 600 mg tablets. 

Day: 2

Medication Dose Route Max duration Details
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

Prior to IFOSFamide infusion.

Recommended daily hydration is 3000 ml per day as oral or IV fluid on day(s) of IFOSFamide and for 24 hours after, or as per institutional practice.
mesna 400 mg/m² intravenous 15 minutes
Instructions:

Immediately prior to IFOSFamide infusion over 15 minutes, or as per institutional practice.
IFOSFamide * 2000 mg/m² Once daily intravenous 120 minutes
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

After IFOSFamide infusion.

Recommended daily hydration is 3000 ml per day as oral or IV fluid on day(s) of IFOSFamide and for 24 hours after, or as per institutional practice.
mesna 800 mg/m² Every four hours oral administration
Instructions:

For 2 doses, at 2 hours and 6 hours after the start of IFOSFamide infusion, or as per institutional practice.

Round dose to closest multiple of 400 mg or 600 mg tablets. 

Day: 3

Medication Dose Route Max duration Details
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

Prior to IFOSFamide infusion.

Recommended daily hydration is 3000 ml per day as oral or IV fluid on day(s) of IFOSFamide and for 24 hours after, or as per institutional practice.
mesna 400 mg/m² intravenous 15 minutes
Instructions:

Immediately prior to IFOSFamide infusion over 15 minutes, or as per institutional practice.
IFOSFamide * 2000 mg/m² Once daily intravenous 120 minutes
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

After IFOSFamide infusion.

Recommended daily hydration is 3000 ml per day as oral or IV fluid on day(s) of IFOSFamide and for 24 hours after, or as per institutional practice.
mesna 800 mg/m² Every four hours oral administration
Instructions:

For 2 doses, at 2 hours and 6 hours after the start of IFOSFamide infusion, or as per institutional practice.

Round dose to closest multiple of 400 mg or 600 mg tablets. 

Day: 4

Medication Dose Route Max duration Details
filgrastim 5 microgram/kg Once daily subcutaneous injection
Instructions:

Give ONCE daily from Day 4 until neutrophil recovery past the nadir, or as per institutional policy for prophylaxis.

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

Cycles 2 to 4 - 21 days

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
etoposide (as phosphate) 250 mg/m² intravenous 60 minutes
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

Prior to iFOSFamide infusion.

Recommended daily hydration is 3000 ml per day as oral or IV fluid on day(s) of IFOSFamide and for 24 hours after, or as per institutional practice.
mesna 400 mg/m² intravenous 15 minutes
Instructions:

Immediately prior to iFOSFamide infusion over 15 minutes, or as per institutional practice.
IFOSFamide * 2000 mg/m² Once daily intravenous 120 minutes
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

After IFOSFamide infusion.

Recommended daily hydration is 3000 ml per day as oral or IV fluid on day(s) of IFOSFamide and for 24 hours after, or as per institutional practice.
mesna 800 mg/m² Every four hours oral administration
Instructions:

For 2 doses, at 2 hours and 6 hours after the start of IFOSFamide infusion, or as per institutional practice.

Round dose to closest multiple of 400 mg or 600 mg tablets. 

Day: 2

Medication Dose Route Max duration Details
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

Prior to iFOSFamide infusion.

Recommended daily hydration is 3000 ml per day as oral or IV fluid on day(s) of IFOSFamide and for 24 hours after, or as per institutional practice.
mesna 400 mg/m² intravenous 15 minutes
Instructions:

Immediately prior to iFOSFamide infusion over 15 minutes, or as per institutional practice.
IFOSFamide * 2000 mg/m² Once daily intravenous 120 minutes
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

After IFOSFamide infusion.

Recommended daily hydration is 3000 ml per day as oral or IV fluid on day(s) of IFOSFamide and for 24 hours after, or as per institutional practice.
mesna 800 mg/m² Every four hours oral administration
Instructions:

For 2 doses, at 2 hours and 6 hours after the start of IFOSFamide infusion, or as per institutional practice.

Round dose to closest multiple of 400 mg or 600 mg tablets. 

Day: 3

Medication Dose Route Max duration Details
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

Prior to iFOSFamide infusion.

Recommended daily hydration is 3000 ml per day as oral or IV fluid on day(s) of IFOSFamide and for 24 hours after, or as per institutional practice.
mesna 400 mg/m² intravenous 15 minutes
Instructions:

Immediately prior to iFOSFamide infusion over 15 minutes, or as per institutional practice.
IFOSFamide * 2000 mg/m² Once daily intravenous 120 minutes
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

After IFOSFamide infusion.

Recommended daily hydration is 3000 ml per day as oral or IV fluid on day(s) of IFOSFamide and for 24 hours after, or as per institutional practice.
mesna 800 mg/m² Every four hours oral administration
Instructions:

For 2 doses, at 2 hours and 6 hours after the start of IFOSFamide infusion, or as per institutional practice.

Round dose to closest multiple of 400 mg or 600 mg tablets. 

Day: 4

Medication Dose Route Max duration Details
filgrastim 5 microgram/kg Once daily subcutaneous injection
Instructions:

Give ONCE daily from Day 4 until neutrophil recovery past the nadir, or as per institutional policy for prophylaxis.

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

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 may be considered
Emetogenicity: Variable
Growth factor support: Recommended for primary prophylaxis
Hydration: Routine hydration recommended
Hypersensitivity / Infusion related reaction risk: High - routine premedication recommended
Mesna uroprotection: Routine mesna uroprotection recommended
Pneumocystis jirovecii pneumonia (PJP) prophylaxis: Routine antibiotic prophylaxis may be considered
Tumour lysis syndrome prophylaxis: Tumour lysis syndrome prophylaxis may be considered

Emetogenicity: MINIMAL day 0; HIGH days 1 to 3.

References

Mappa S, Marturano E, Licata G, Frezzato M, Frungillo N, Ilariucci F, Stelitano C, Ferrari A, Sorarù M, Vianello F, Baldini L, Proserpio I, Foppoli M, Assanelli A, Reni M, Caligaris-Cappio F, Ferreri AJ. Salvage chemoimmunotherapy with Rituximab, ifosfamide and etoposide (R-IE regimen) in patients with primary CNS lymphoma relapsed or refractory to high-dose methotrexate-based chemotherapy. Hematol Oncol. 2013 Sep;31(3):143-50. doi: 10.1002/hon.2037. Epub 2012 Nov 14., PMID: 23161567

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.