regimen-monograph

CEF; CEF-TRAS

Regimen Category

Standard

Funding Program

ODB - General Benefit

Drugs Used

cyclophosphamide , EPIrubicin , fluorouracil , trastuzumab

A - Regimen Name

CEF Regimen

Cyclophosphamide (oral)-EPIrubicin-Fluorouracil

CEF-TRAS Regimen

Cyclophosphamide (oral)-EPIrubicin-Fluorouracil then Trastuzumab

Disease Site

Breast

Intent

Adjuvant
Neoadjuvant

Regimen Category

Standard : Standard therapy endorsed by the Disease Site Group or a regimen widely used by most Regional Cancer Centres in this disease site. The category is unrelated to the source or availability of funding.

Rationale and Uses

Neoadjuvant treatment for non-metastatic breast cancer (inoperable locally advanced, inflammatory or to downsize tumour pre-surgery) or Adjuvant therapy for node-positive and high risk node-negative breast cancer patients

Trastuzumab may be used after the completion of CEF if applicable (HER2-positive, adequate cardiac function). In addition, trastuzumab may be used for patients with node negative HER2 positive tumours 1mm - ≤1cm; LVEF must be ≥ 55% (>50 yrs) or ≥ 50% (≤50 yrs). Refer to the TRAS (Breast -Adjuvant) regimen and funding details on NDFP/EBP forms.

Supplementary Public Funding

cyclophosphamide
ODB - General Benefit (cyclophosphamide - oral tablets)

EPIrubicin
New Drug Funding Program (Epirubicin - Adjuvant Treatment for Breast Cancer)

EPIrubicin
New Drug Funding Program (Epirubicin - Neoadjuvant Treatment for Non-Metastatic Breast Cancer)

trastuzumab
New Drug Funding Program (Trastuzumab - Adjuvant Treatment for HER2_neu-Overexpressing Primary Breast Cancer)

trastuzumab
Evidence Building Program (Trastuzumab (EBP) - Adjuvant Treatment for Breast Cancer)

trastuzumab
Evidence Building Program (Trastuzumab (EBP) - Adjuvant Treatment for Breast Cancer Supplemental)

B - Drug Regimen

cyclophosphamide

75 mg /m²

Daily x 14 days

_{(Outpatient prescription in multiples of 25mg or 50mg tablets)}

EPIrubicin

(Round to nearest 1 mg)

60 mg /m²

Day 1 and Day 8

fluorouracil

(Round to nearest 25 mg)

500 mg /m²

Day 1 and Day 8

For patients with HER2 positive tumours, Trastuzumab may be given for one year, after the completion of CEF:

trastuzumab

Refer to TRAS (Breast - Adjuvant) regimen for details.

C - Cycle Frequency

REPEAT EVERY 28 DAYS

For a Usual Total of 6 Cycles

Trastuzumab: Refer to TRAS (Breast - Adjuvant) regimen for details.

D - Premedication and Supportive Measures

Antiemetic Regimen:

Moderate

Other Supportive Care:

Routine prophylaxis with Co-trimoxazole or Ciprofloxacin for the duration of the chemotherapy course
Co-trimoxazole 2 tabs bid or Ciprofloxacin 500mg bid; some centres prescribe on days 10 to 24 only

E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. The following recommendations are in use at some centres.

Dosage with toxicity

Hematologic Toxicities: See Appendix 6 for general recommendations.

Toxicity Type / Counts x 10⁹/L		Toxicity Type / Counts x 10⁹/L	Fluorouracil (% previous dose)	Epirubicin (% previous dose)		Cyclophosphamide (% previous dose)
ANC <1.5	Or	Platelet < 100	Hold *
Febrile Neutropenia, or Grade 4 ANC ≥ 7 d	Or	Thrombocytopenic bleeding	Hold *, then 75% (or consider GCSF – for isolated neutropenia)
ANC ≥ 1.5	And	Platelet ≥ 100	100%
Cardiotoxicity**			Discontinue		Discontinue	Caution
Grade 3 related organ / non-hematologic			*75% for suspect drug(s)
Grade 4 related organ / non-hematologic			Discontinue

_{*Retreat when toxicities have recovered to ≤ grade 2, platelets ≥ 100 x 10⁹/L, and ANC ≥ 1.5 x 10⁹/L.}
_{**including any signs and symptoms of heart failure, greater than 10% decline in LVEF to below the lower limit of normal, a greater than 20% decline in LVEF from any level, or LVEF ≤ 45%.}

Hepatic Impairment

AST/ALT		Bilirubin	Epirubicin (% previous dose)	Fluorouracil (% previous dose)	Cyclophosphamide (% previous dose)
2-4 x ULN	Or	1-2 x ULN	50%	No change	No change
>4 X ULN	Or	2-4 X ULN	25%	No change	Caution
		> 4 X ULN	Discontinue	Discontinue	Caution

Renal Impairment

Creatinine Clearance (mL/min)	Fluorouracil (% previous dose)	Epirubicin (% previous dose)	Cyclophosphamide (% previous dose)
>30 – 50	100%	100%	100%
10 – 30	consider dose ↓		50-75%
< 10	↓ dose		50% or OMIT

F - Adverse Effects

Refer to cyclophosphamide, EPIrubicin, fluorouracil drug monograph(s) for additional details of adverse effects

Refer to trastuzumab drug monograph for adverse effect details (not listed below).

Bolus 5FU regimens have more myelosuppression and GI effects but less Hand-Foot Syndrome, compared to prolonged infusions.

Most Common Side Effects

Less Common Side Effects, but may be
Severe or Life-Threatening

Nausea and vomiting
Cystitis
Myelosuppression ± infection
Stomatitis and diarrhea
Alopecia
Fatigue
Amenorrhea

· Pneumonitis, pulmonary fibrosis

· SIADH, renal failure

· DIC, hemolytic uremic syndrome

· Secondary leukemia or cancers

· Venous/arterial thromboembolism

· Cardiotoxicity, AMI, arrhythmia

G - Interactions

Refer to cyclophosphamide, EPIrubicin, fluorouracil drug monograph(s) for additional details

H - Drug Administration and Special Precautions

Refer to cyclophosphamide, EPIrubicin, fluorouracil drug monograph(s) for additional details

I - Recommended Clinical Monitoring

Recommended Clinical Monitoring

Clinical toxicity assessment (including stomatitis, pulmonary, cardiotoxicity, infection, local toxicity, cystitis).
CBC before each cycle
Baseline and regular liver and renal function tests
Cardiac examination especially with risk factors (including prior therapy with Doxorubicin, Mitoxantrone or other cardiac drug), or a cumulative Epirubicin dose of > 900mg/m² .
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

J - Administrative Information

Approximate Patient Visit

CEF

1 hour

CEF-TRAS

CEF: 1 hour; TRAS: 1.5 hours (1st cycle); 0.5 hour (subsequent cycles)

Pharmacy Workload (average time per visit)

CEF

15 minutes

Nursing Workload (average time per visit)

CEF

69.8 minutes

K - References

Levine MN, Bramwell VH, Pritchard KI, et al. Randomized trial of intensive Cyclophosphamide, Epirubicin, Fluorouracil chemotherapy compared with Cyclophosphamide, Methotrexate, and Fluorouracil in premenopausal women with node-positive breast cancer. J Clin Oncol 1998 Aug; 16(8): 2651-2658.

PEBC Advice Documents or Guidelines

The Prophylactic Use of Filgrastim in Patients with Breast Cancer

October 2017 Formatted public funding info

L - Other Notes

If Cyclophosphamide is given IV, see FEC100 regimen.

M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.

Last Updated: July 21, 2026

The information on this website is intended for informational purposes only and is not a substitute for medical advice. Always consult your health care provider if you have questions or concerns. The use of the information on this website does not create a physician-patient relationship between Ontario Health and you.
Ontario Health is committed to ensuring accessible services and communications to individuals with disabilities. To receive any information on this website in an alternate format, please contact Ontario Health’s Communications Department at: 1-877-280-8538,TTY 1-800-855-0511, or by email at info@ontariohealth.ca.