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Systemic Anti-Cancer Therapy Regimen Library

Home > CRC Metastatic - mFOLFIRI [irinotecan, foliNIc acid and fluorouracil] [high dose foliNIc acid], CETUximab [Q2W] and encorafenib

CRC Metastatic - mFOLFIRI [irinotecan, foliNIc acid and fluorouracil] [high dose foliNIc acid], CETUximab [Q2W] and encorafenib

Treatment Overview

Cycle 1 (and all further cycles) - 14 days

Cycle length:
14

encorafenib:

  • Clinicians may choose to vary the BRAF inhibitor in the regimen based on individual patient circumstances (e.g. substituting encorafenib with dabrafenib due to current availability or cost).

Cycle details

Cycle 1 (and all further cycles) - 14 days

Medication Dose Route Days Max Duration
doxycycline * 100 mg Once daily oral administration 0
hydrocortisone * 1 % Once daily topical administration 0
cetostearyl alcohol + paraffin liquid + paraffin soft white 50 g Once daily topical administration 0
avobenzone + homosalate + octisalate + octocrilene + oxybenzone 50 g topical administration 0
encorafenib 300 mg Once daily oral administration 1 to 14
dexamethasone * 8 mg oral administration 1, 2, 3
ondansetron 8 mg oral administration 1
loratadine * 10 mg oral administration 1
CETUximab 500 mg/m² intravenous 1 120 minutes
irinotecan 180 mg/m² intravenous 1 90 minutes
atropine sulfate * 600 microgram intravenous 1 2 minutes
foliNIc acid (as calcium folinate) 400 mg/m² intravenous 1 90 minutes
fluorouracil 2400 mg/m² intravenous 1 46 hours Min: 46 hours
ondansetron 8 mg oral administration 1
cyclIZINE 50 mg Three times daily oral administration 1
loperamide 2 mg oral administration 1

encorafenib:

  • Clinicians may choose to vary the BRAF inhibitor in the regimen based on individual patient circumstances (e.g. substituting encorafenib with dabrafenib due to current availability or cost).

Full details

Cycle 1 (and all further cycles) - 14 days

Day: 0

Medication Dose Route Max duration Details
doxycycline * 100 mg Once daily oral administration
Instructions:
  • To prevent rash.
  • Commence taking the day before cetuximab and continue for 6 weeks or as per institutional policy. If no rash develops after 6 weeks, consider stopping.
  • Take each dose with food and a large glass of water. Swallow whole, do not crush or chew. Remain sitting upright or standing for at least 30 minutes afterwards. Do not take indigestion remedies, iron or calcium preparations within 2 hours of taking this medicine.
  • Protect yourself from too much natural or artificial sunlight while being treated with this medicine.
hydrocortisone * 1 % Once daily topical administration
Instructions:
  • To prevent rash.
  • Apply to the face, hands, feet, neck, back and chest at bedtime or as directed by your oncologist.
  • If no rash develops after 6 weeks, consider stopping.
cetostearyl alcohol + paraffin liquid + paraffin soft white 50 g Once daily topical administration
Instructions:
  • Apply as a moisturiser to the face, hands, feet, neck, back and chest each morning or as directed by your oncologist.
  • Whilst this is a subsidised preparation, other moisturisers may also be suitable.
  • Quantity is approximate only, prescriber discretion required.
avobenzone + homosalate + octisalate + octocrilene + oxybenzone 50 g topical administration
Instructions:
  • SPF 50+ Sunscreen—apply to skin 30 minutes before going outdoors as directed by your oncologist.
  • Certified condition for subsidy. Whilst this is the subsidised preparation, alternative SPF 50+ sunscreen preparations may also be suitable.
  • Quantity is approximate only, prescriber discretion required.

Day: 1

Medication Dose Route Max duration Details
encorafenib 300 mg Once daily oral administration
Instructions:

Swallow whole, do not crush or chew. Avoid grapefruit and its juice.
dexamethasone * 8 mg oral administration
Instructions:

ONE hour prior to cetuximab with food.
ondansetron 8 mg oral administration
Instructions:
ONE hour prior to chemotherapy.
loratadine * 10 mg oral administration
Instructions:

ONE hour prior to cetuximab.

CETUximab 500 mg/m² intravenous 120 minutes
Instructions:
  • Administer over 120 minutes; if initial and all previous doses are well tolerated, evidence from clinical trials support administration of subsequent doses over 60 minutes.
  • An observation period of 60 minutes post-infusion is recommended prior to administration of further systemic anti-cancer treatment.
irinotecan 180 mg/m² intravenous 90 minutes
Instructions:

To run concurrently with folinic acid.
atropine sulfate * 600 microgram intravenous 2 minutes
Instructions:

Only if required for acute diarrhoea or cholinergic symptoms.

  • Alternatively, dose may be administered subcutaneously.
  • 600 microgram = 0.6 mg.
  • Some centres may wish to give a reduced dose of 300 microgram (= 0.3 mg) in line with institutional policy.
  • Dose may be repeated up to a maximum dose of 1200 microgram (= 1.2 mg).
foliNIc acid (as calcium folinate) 400 mg/m² intravenous 90 minutes
Instructions:

To run concurrently with irinotecan.
fluorouracil 2400 mg/m² intravenous 46 hours Min: 46 hours
Instructions:
Continuous infusion via pump over 46 hours.
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 encorafenib due to potential risk of QT prolongation.
loperamide 2 mg oral administration
Instructions:
Take TWO capsules (=4 mg) at onset of loose bowel motions and a further ONE capsule (=2 mg) for every loose bowel motion (maximum of EIGHT capsules in 24 hours), or use as directed by oncologist or haematologist.

Day: 2

Medication Dose Route Max duration Details
encorafenib 300 mg Once daily oral administration
Instructions:

Swallow whole, do not crush or chew. Avoid grapefruit and its juice.
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

  • This dose may be reduced or omitted at clinician's discretion. 

Day: 3

Medication Dose Route Max duration Details
encorafenib 300 mg Once daily oral administration
Instructions:

Swallow whole, do not crush or chew. Avoid grapefruit and its juice.
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

  • This dose may be reduced or omitted at clinician's discretion.

Day: 4

Medication Dose Route Max duration Details
encorafenib 300 mg Once daily oral administration
Instructions:

Swallow whole, do not crush or chew. Avoid grapefruit and its juice.

Day: 5

Medication Dose Route Max duration Details
encorafenib 300 mg Once daily oral administration
Instructions:

Swallow whole, do not crush or chew. Avoid grapefruit and its juice.

Day: 6

Medication Dose Route Max duration Details
encorafenib 300 mg Once daily oral administration
Instructions:

Swallow whole, do not crush or chew. Avoid grapefruit and its juice.

Day: 7

Medication Dose Route Max duration Details
encorafenib 300 mg Once daily oral administration
Instructions:

Swallow whole, do not crush or chew. Avoid grapefruit and its juice.

Day: 8

Medication Dose Route Max duration Details
encorafenib 300 mg Once daily oral administration
Instructions:

Swallow whole, do not crush or chew. Avoid grapefruit and its juice.

Day: 9

Medication Dose Route Max duration Details
encorafenib 300 mg Once daily oral administration
Instructions:

Swallow whole, do not crush or chew. Avoid grapefruit and its juice.

Day: 10

Medication Dose Route Max duration Details
encorafenib 300 mg Once daily oral administration
Instructions:

Swallow whole, do not crush or chew. Avoid grapefruit and its juice.

Day: 11

Medication Dose Route Max duration Details
encorafenib 300 mg Once daily oral administration
Instructions:

Swallow whole, do not crush or chew. Avoid grapefruit and its juice.

Day: 12

Medication Dose Route Max duration Details
encorafenib 300 mg Once daily oral administration
Instructions:

Swallow whole, do not crush or chew. Avoid grapefruit and its juice.

Day: 13

Medication Dose Route Max duration Details
encorafenib 300 mg Once daily oral administration
Instructions:

Swallow whole, do not crush or chew. Avoid grapefruit and its juice.

Day: 14

Medication Dose Route Max duration Details
encorafenib 300 mg Once daily oral administration
Instructions:

Swallow whole, do not crush or chew. Avoid grapefruit and its juice.

Supportive Care Factors

Factor Value
Diarrhoea risk: Anti-diarrhoeals are usually prescribed with this treatment
Emetogenicity: Variable
Hypersensitivity / Infusion related reaction risk: High - routine premedication recommended

Emetogenicity: 

  • MEDIUM day 1.
  • MINIMAL to LOW days 2 to 14 (encorafenib). Routine antiemetic premedication is not usually required; an individualised approach is appropriate.

References

Elez E, Yoshino T, Shen L, et al; BREAKWATER Trial Investigators. Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated Colorectal Cancer. N Engl J Med. 2025 Jun 26;392(24):2425-2437. , PMID: 40444708

Nott, L., M. Khattak, T. Price, et al. Cancer Council Australia Colorectal Cancer Guidelines Working Party. [Version URL: https://wiki.cancer.org.au/australiawiki/index.php?oldid=173114, cited 2018 Apr 16]. Available from https://wiki.cancer.org.au/australia/Guidelines:Colorectal_cancer/Systemic_therapy_molecular_pathology. In: Cancer Council Australia Colorectal Cancer Guidelines Working Party. Cl

Peng C, Saffo S, Oberstein PE, et al. Omission of 5-Fluorouracil Bolus From Multidrug Regimens for Advanced Gastrointestinal Cancers: A Multicenter Cohort Study. J Natl Compr Canc Netw. 2024 Sep 5;22(8):521-527., PMID: 39236754

Array BioPharma Inc. Braftovi US prescribing information December 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/210496s018lbl.pdf (Accessed 21 November 2025)

Healthcare Logistics Ltd. Erbitux New Zealand Data Sheet 30 January 2024. https://www.medsafe.govt.nz/profs/Datasheet/e/Erbituxinf.pdf (Accessed 21 November 2025).

Hofheinz RD, Deplanque G, Komatsu Y, et al. Recommendations for the Prophylactic Management of Skin Reactions Induced by Epidermal Growth Factor Receptor Inhibitors in Patients With Solid Tumors. Oncologist. 2016;21(12):1483-1491. doi:10.1634/theoncologist.2016-0051., PMID: 27449521

Lacouture ME, Anadkat MJ, Bensadoun RJ, et al; MASCC Skin Toxicity Study Group. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer. 2011 Aug;19(8):1079-95., PMID: 21630130

Deplanque G, Gervais R, Vergnenegre A, et al. Doxycycline for prevention of erlotinib-induced rash in patients with non-small-cell lung cancer (NSCLC) after failure of first-line chemotherapy: A randomized, open-label trial. Journal of the American Academy of Dermatology. 2016 Jun 1;74(6):1077-85., PMID: 26946985

Dika, E., & Patrizi, A. (2017). Prevention of erlotinib-induced folliculitis with doxycycline. Dermatologic therapy, 30(1), https://doi.org/10.1111/dth.12419., PMID: 27592506

Regimen details sometimes vary slightly from the published literature after recommendation by expert committee consensus.

* 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.