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Home > LYM NHL B-cell - DA-R-EPOCH [Dose-adjusted RITUximab, etoposide, prEDNIsone, vinCRISTine, CYCLOPHOSPHamide and DOXOrubicin] [9 levels] > LYM - DA-R-EPOCH LEVEL 1
This regimen is a component of LYM NHL B-cell - DA-R-EPOCH [Dose-adjusted RITUximab, etoposide, prEDNIsone, vinCRISTine, CYCLOPHOSPHamide and DOXOrubicin] [9 levels]

LEVEL 1: Starting Level (LYM NHL B-cell - DA-R-EPOCH [Dose-adjusted RITUximab, etoposide, prEDNIsone, vinCRISTine, CYCLOPHOSPHamide and DOXOrubicin] [9 levels])

Treatment Overview

LEVEL 1: Use for Cycle 1 (Starting level).

Give up to 8 cycles of LEVEL 1 or use appropriate level as per neutrophil and platelet counts (see Table in Additional details tab above).


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 - 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.

DOXOrubicin, etoposide (as phosphate) and vinCRISTine:

  • May be admixed and administered as a 96 hour infusion.
  • Consult latest literature for stability information of an admixed solution.
  • Consider accuracy of infusion device, infusion time must not be less than 90 hours or longer than 100 hours (i.e. +/- 5% of total time of 96 hours). 
  • A central venous access device is required for administration of the 96 hour infusion.

vinCRISTine: Dose capping of vinCRISTine to 2 mg (flat dose) over 96 hours is not included in published DA-R-EPOCH protocol but could be considered for patients over 50 years of age.


filgrastim:

  • Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery past nadir, or as per institutional practice.
  • The original published data uses daily filgrastim. Small single centre predominantly retrospective publications, support the use of pegFILGRASTIM 6 mg subcutaneously administered 24 to 48 hours after chemotherapy as an alternative to daily filgrastim and this may be considered.

Cycle details

Cycles 1 to 8 - 21 days

Medication Dose Route Days Max Duration
prEDNISone * 60 mg/m² Twice daily oral administration 1 to 5
paracetamol * 1000 mg flat dosing oral administration 1
loratadine * 10 mg oral administration 1
RITUximab 375 mg/m² intravenous 1 6 hours
DOXOrubicin * 10 mg/m² Once daily intravenous 1 to 4 24 hours Min: 24 hours
vinCRISTine * 0.4 mg/m² Once daily intravenous 1 to 4 24 hours Min: 24 hours
etoposide (as phosphate) 50 mg/m² Once daily intravenous 1 to 4 24 hours Min: 24 hours
CYCLOPHOSPHamide 750 mg/m² intravenous 5 60 minutes
filgrastim 5 microgram/kg Once daily subcutaneous injection 6

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.

DOXOrubicin, etoposide (as phosphate) and vinCRISTine:

  • May be admixed and administered as a 96 hour infusion.
  • Consult latest literature for stability information of an admixed solution.
  • Consider accuracy of infusion device, infusion time must not be less than 90 hours or longer than 100 hours (i.e. +/- 5% of total time of 96 hours). 
  • A central venous access device is required for administration of the 96 hour infusion.

vinCRISTine: Dose capping of vinCRISTine to 2 mg (flat dose) over 96 hours is not included in published DA-R-EPOCH protocol but could be considered for patients over 50 years of age.


filgrastim:

  • Give filgrastim 5 microgram/kg subcutaneously ONCE daily from day 6 until neutrophil recovery past nadir, or as per institutional practice.
  • The original published data uses daily filgrastim. Small single centre predominantly retrospective publications, support the use of pegFILGRASTIM 6 mg subcutaneously administered 24 to 48 hours after chemotherapy as an alternative to daily filgrastim and this may be considered.

Full details

Cycles 1 to 8 - 21 days

Day: 1

Medication Dose Route Max duration Details
prEDNISone * 60 mg/m² Twice daily oral administration
Instructions:

Give first dose at least ONE hour prior to RITUximab with food.
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:

First administration: 

  • 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.

Further administrations: 

  • 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.
DOXOrubicin * 10 mg/m² Once daily intravenous 24 hours Min: 24 hours
Instructions:
  • Continuous infusion over 24 hours.
  • Administer daily for 4 days, total dose 40 mg/m2 over 96 hours.
  • Alternatively, DOXOrubicin 40 mg/m2 over 96 hours may be administered via continuous venous infusion loaded with vinCRISTine and etoposide (as phosphate).
  • Warning vesicant—administer as per institutional policy.
vinCRISTine * 0.4 mg/m² Once daily intravenous 24 hours Min: 24 hours
Instructions:
  • Continuous infusion over 24 hours.
  • Administer daily for 4 days, total dose 1.6 mg/m2 over 96 hours.
  • Alternatively, vinCRISTine 1.6 mg/m2 over 96 hours may be administered via continuous venous infusion loaded with DOXOrubicin and etoposide (as phosphate).
  • Warning vesicant—administer as per institutional policy.
etoposide (as phosphate) 50 mg/m² Once daily intravenous 24 hours Min: 24 hours
Instructions:
  • Continuous infusion over 24 hours.
  • Administer daily for 4 days, total dose 200 mg/m2 over 96 hours.
  • Alternatively, etoposide (as phosphate) 200 mg/m2 over 96 hours may be administered via continuous venous infusion loaded with DOXOrubicin and vinCRISTine.

Day: 2

Medication Dose Route Max duration Details
prEDNISone * 60 mg/m² Twice daily oral administration
Instructions:

Take with food.
DOXOrubicin * 10 mg/m² Once daily intravenous 24 hours Min: 24 hours
Instructions:
  • Continuous infusion over 24 hours.
  • Administer daily for 4 days, total dose 40 mg/m2 over 96 hours.
  • Alternatively, DOXOrubicin 40 mg/m2 over 96 hours may be administered via continuous venous infusion loaded with vinCRISTine and etoposide (as phosphate).
  • Warning vesicant—administer as per institutional policy.
vinCRISTine * 0.4 mg/m² Once daily intravenous 24 hours Min: 24 hours
Instructions:
  • Continuous infusion over 24 hours.
  • Administer daily for 4 days, total dose 1.6 mg/m2 over 96 hours.
  • Alternatively, vinCRISTine 1.6 mg/m2 over 96 hours may be administered via continuous venous infusion loaded with DOXOrubicin and etoposide (as phosphate).
  • Warning vesicant—administer as per institutional policy.
etoposide (as phosphate) 50 mg/m² Once daily intravenous 24 hours Min: 24 hours
Instructions:
  • Continuous infusion over 24 hours.
  • Administer daily for 4 days, total dose 200 mg/m2 over 96 hours.
  • Alternatively, etoposide (as phosphate) 200 mg/m2 over 96 hours may be administered via continuous venous infusion loaded with DOXOrubicin and vinCRISTine.

Day: 3

Medication Dose Route Max duration Details
prEDNISone * 60 mg/m² Twice daily oral administration
Instructions:

Take with food.
DOXOrubicin * 10 mg/m² Once daily intravenous 24 hours Min: 24 hours
Instructions:
  • Continuous infusion over 24 hours.
  • Administer daily for 4 days, total dose 40 mg/m2 over 96 hours.
  • Alternatively, DOXOrubicin 40 mg/m2 over 96 hours may be administered via continuous venous infusion loaded with vinCRISTine and etoposide (as phosphate).
  • Warning vesicant—administer as per institutional policy.
vinCRISTine * 0.4 mg/m² Once daily intravenous 24 hours Min: 24 hours
Instructions:
  • Continuous infusion over 24 hours.
  • Administer daily for 4 days, total dose 1.6 mg/m2 over 96 hours.
  • Alternatively, vinCRISTine 1.6 mg/m2 over 96 hours may be administered via continuous venous infusion loaded with DOXOrubicin and etoposide (as phosphate).
  • Warning vesicant—administer as per institutional policy.
etoposide (as phosphate) 50 mg/m² Once daily intravenous 24 hours Min: 24 hours
Instructions:
  • Continuous infusion over 24 hours.
  • Administer daily for 4 days, total dose 200 mg/m2 over 96 hours.
  • Alternatively, etoposide (as phosphate) 200 mg/m2 over 96 hours may be administered via continuous venous infusion loaded with DOXOrubicin and vinCRISTine.

Day: 4

Medication Dose Route Max duration Details
prEDNISone * 60 mg/m² Twice daily oral administration
Instructions:

Take with food.
DOXOrubicin * 10 mg/m² Once daily intravenous 24 hours Min: 24 hours
Instructions:
  • Continuous infusion over 24 hours.
  • Administer daily for 4 days, total dose 40 mg/m2 over 96 hours.
  • Alternatively, DOXOrubicin 40 mg/m2 over 96 hours may be administered via continuous venous infusion loaded with vinCRISTine and etoposide (as phosphate).
  • Warning vesicant—administer as per institutional policy.
vinCRISTine * 0.4 mg/m² Once daily intravenous 24 hours Min: 24 hours
Instructions:
  • Continuous infusion over 24 hours.
  • Administer daily for 4 days, total dose 1.6 mg/m2 over 96 hours.
  • Alternatively, vinCRISTine 1.6 mg/m2 over 96 hours may be administered via continuous venous infusion loaded with DOXOrubicin and etoposide (as phosphate).
  • Warning vesicant—administer as per institutional policy.
etoposide (as phosphate) 50 mg/m² Once daily intravenous 24 hours Min: 24 hours
Instructions:
  • Continuous infusion over 24 hours.
  • Administer daily for 4 days, total dose 200 mg/m2 over 96 hours.
  • Alternatively, etoposide (as phosphate) 200 mg/m2 over 96 hours may be administered via continuous venous infusion loaded with DOXOrubicin and vinCRISTine.

Day: 5

Medication Dose Route Max duration Details
prEDNISone * 60 mg/m² Twice daily oral administration
Instructions:

Take with food.
CYCLOPHOSPHamide 750 mg/m² intravenous 60 minutes

Day: 6

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

Give ONCE daily from Day 6 until neutrophil recovery past the nadir, or as per institutional practice.

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

Additional details

Section 1: Subsequent cycle levels determined by neutrophil and platelet counts as per Table:

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
Constipation risk: laxatives are usually prescribed
Emetogenicity: Medium
Gastroprotection: Gastroprotection may be considered
Growth factor support: Recommended for primary prophylaxis
Hypersensitivity / Infusion related reaction risk: High - routine premedication recommended
Pneumocystis jirovecii pneumonia (PJP) prophylaxis: Routine antibiotic prophylaxis recommended
Tumour lysis syndrome prophylaxis: Tumour lysis syndrome prophylaxis is recommended

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

References

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

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.