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regimen-monograph
EPIR-CMF
Intent
Adjuvant
Regimen Category
Local
Drugs Used
A - Regimen Name
EPIR-CMF Regimen
EPIrubicin then Cyclophosphamide-Methotrexate-Fluorouracil
Disease Site
Breast
Intent
Adjuvant
Regimen Category
Local : A regimen not widely used by Regional Cancer Centres in this disease site.
Rationale and Uses
Adjuvant therapy for node-positive and high risk node-negative breast cancer patients
B - Drug Regimen
| EPIrubicin
(Round to nearest 1mg) |
100 mg /m² | IV | Day 1 (FIRST 4 CYCLES ONLY) |
|
THEN modified CMF IV X 4 CYCLES OR CMF PO X 4 CYCLES Modified CMF IV:
|
|||
| cyclophosphamide
(Round to nearest 10mg) |
750 mg /m² | IV | Day 1 |
| methotrexate
(Round to nearest 5mg) |
50 mg /m² | IV | Day 1 |
| fluorouracil
(Round to nearest 25mg) |
600 mg /m² | IV | Day 1 |
|
|
|||
| cyclophosphamide
(Round to nearest 25mg) |
100 mg /m² | PO | Daily for 14 days |
|
(Outpatient prescription in 25mg or 50mg tablets)
|
|||
| methotrexate
(Round to nearest 5mg) |
40 mg /m² | IV | Days 1 and 8 |
| fluorouracil
(Round to nearest 25mg) |
600 mg /m² | IV | Days 1 and 8 |
C - Cycle Frequency
EPIRUBICIN Cycles REPEAT EVERY 21 DAYS
CMF IV Cycles REPEAT EVERY 21 DAYS or
CMF PO Cycles REPEAT EVERY 28 DAYS
D - Premedication and Supportive Measures
Antiemetic Regimen:
Moderate (Epirubicin or CMF IV cycles)
Moderate (CMF PO (Days 1 and 8))
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
EPIRUBICIN and CMF CYCLES:
Hematologic Toxicities: See Appendix 6 for general recommendations.
Hepatic Impairment
Epirubicin Cycles:
Bilirubin |
EPIrubicin (% previous dose) |
1-1.5 x ULN |
50-100% |
1.5-2 x ULN |
50% |
2-4 x ULN |
25-50% |
>4 x ULN |
OMIT |
CMF CYCLES:
Bilirubin |
% usual dose |
2-3 x ULN |
Reduce Methotrexate to 75% |
>3 x ULN |
OMIT Methotrexate |
> 4 x ULN |
OMIT Fluorouracil |
Renal Impairment
CMF CYCLES:
Creatinine Clearance (mL/sec) |
Action | |
| 0.2-0.8 | Reduce methotrexate to 50% dose | |
| <0.3 | Reduce cyclophosphamide to 50% dose (suggested) | |
| <0.2 | OMIT methotrexate | |
F - Adverse Effects
Refer to EPIrubicin, cyclophosphamide, methotrexate, fluorouracil drug monograph(s) for additional details of adverse effects
Bolus 5FU regimens have more myelosuppression and GI effects but less Hand-Foot Syndrome, compared to prolonged infusions.
Most Frequently Occurring Adverse Effects
- Nausea and vomiting
- Cystitis
- Myelosuppression
- Cardiotoxicity
- Stomatitis and diarrhea
- Vesicant
- Rash
- Alopecia
G - Interactions
Refer to EPIrubicin, cyclophosphamide, methotrexate, fluorouracil drug monograph(s) for additional details
H - Drug Administration and Special Precautions
Refer to EPIrubicin, cyclophosphamide, methotrexate, fluorouracil drug monograph(s) for additional details
I - Recommended Clinical Monitoring
Recommended Clinical Monitoring
EPIRUBICIN CYCLES:
- Clinical toxicity assessment (including stomatitis, cardiotoxicity, local toxicity)
- 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 cardiotoxic drug), or a cumulative epirubicin dose of > 900 mg/m2
CMF CYCLES:
- Clinical toxicity (including stomatitis, cystitis) assessment
- CBC before each cycle
- Baseline and regular liver function tests
- Baseline and regular renal function tests
- Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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J - Administrative Information
Approximate Patient Visit
EPIR: 1 hour; CMF: 1 hour; CMF(PO); 0.5 hour
K - References
Poole CJ, Earl HM, Hiller L, et al. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med 2006;355(18):1851-62.
September 2012: Modified sections A, D and K.
PEBC Advice Documents or Guidelines
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
