regimen-monograph

CMF+TRAS; CMF

Regimen Category

Local

Drugs Used

cyclophosphamide , methotrexate , fluorouracil , trastuzumab

A - Regimen Name

CMF Regimen

Cyclophosphamide-Methotrexate-Fluorouracil

CMF+TRAS Regimen

Cyclophosphamide-Methotrexate-Fluorouracil,Trastuzumab

Disease Site

Breast

Intent

Neoadjuvant
Adjuvant

Regimen Category

Local : A regimen not widely used by Regional Cancer Centres in this disease site.

Rationale and Uses

Neoadjuvant treatment for locally advanced breast cancer or adjuvant therapy for node-positive and high risk node-negative breast cancer patients

Trastuzumab may be used concurrently with or after completion of CMF 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

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

(Round to nearest 10 mg)

600 mg /m²

Day 1

methotrexate

(Round to nearest 5 mg)

40 mg /m²

Day 1

fluorouracil

(Round to nearest 25 mg)

600 mg /m²

Day 1

For patients with HER2 positive tumours, Trastuzumab may be given for one year, starting either concurrently or after completion of CMF.

trastuzumab

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

C - Cycle Frequency

REPEAT EVERY 21 DAYS

For 6 cycles

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

D - Premedication and Supportive Measures

Antiemetic Regimen:

Moderate

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.

Worst Toxicity Type / Counts x 10⁹/L in Prior Cycle	Cyclophosphamide (% previous dose)	Methotrexate (% previous dose)	Fluorouracil (% previous dose)
Febrile Neutropenia, or Thrombocytopenic bleeding, or Grade 4 ANC ≥ 7 d	75% * (or consider GCSF for isolated neutropenia)
Grade 3 related organ	75% for suspect drug(s)*
Grade 4 related organ, Any grade pneumonitis, cardiac or viral reactivation	Discontinue suspect drug(s)

_{*Do not retreat until toxicity has recovered to ≤ grade 2, platelets ≥ 100 x 10⁹/L, and ANC ≥ 1.5 x 10⁹/L.}

Hepatic Impairment

AST/ALT		Bilirubin	Methotrexate (% previous)	Fluorouracil (% previous)	Cyclophosphamide (% previous)
2-4 x ULN	OR	2-4 x ULN	50% or Discontinue	No change	No change
>4 X ULN	AND	< 4 X ULN	Discontinue	No change	Caution
		> 4 X ULN	Discontinue	Discontinue	Caution

Renal Impairment

Creatinine Clearance (mL/min)	Cyclophosphamide (% previous dose)	Methotrexate (% previous dose)	Fluorouracil (% previous dose)
>50 – 80	100%	50-75%	100%
>30 – 50	100%	OMIT	100%
10 – 30	50-75%		Consider dose ↓
< 10	50% or OMIT		Consider dose ↓

F - Adverse Effects

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

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

Most Common Side Effects

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

Myelosuppression ± infection / bleeding
Cystitis
Nausea and vomiting
Diarrhea
Stomatitis, anorexia
Alopecia
Nephrotoxicity
↑ LFTs
Reproductive risk
Conjunctivitis

· SIADH

· Cardiac, AMI, arrhythmia

· Thromboembolism, DIC, HUS, VOD, hemolysis

· Secondary malignancies

· Pneumonitis

· Leukoencephalopathy (may be delayed)

· Severe rash, photosensitivity

· Rhabdomyolysis

· Pancreatitis

G - Interactions

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

H - Drug Administration and Special Precautions

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

I - Recommended Clinical Monitoring

Recommended Clinical Monitoring

Clinical toxicity assessment (including GI, cystitis, cardiac, infection).
CBC before each cycle
Baseline and regular liver function tests
Baseline and regular renal function tests and urinalysis
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

J - Administrative Information

Approximate Patient Visit

CMF

1 hour

CMF+TRAS

CMF: 1 hour
TRAS: 1.5 hours (first dose), 0.5 hour (subsequent doses)

K - References

Fisher B, Brown AM, Dimitrov NV, et al. Two months of doxorubicin/cyclophosphamide with and without interval reinduction therapy compared with six months of Cyclophosphamide, Methotrexate and 5-Fluorouracil in node-positive breast cancer patients with tamoxifen non-responsive tumors: results from the NSABP B-15. J. Clin Oncol 1990 Sep;8(9): 1483-96.

Zambetti M, Bonadonna G, Valagussa P, et al, Adjuvant CMF for node-negative and estrogen receptor-negative breast cancer patients. J Natl Cancer Inst Monogr, 1992; 11: 77-83.

October 2017 Updated antiemetic classification

L - Other Notes

If Cyclophosphamide given PO, see regimen CMF(PO)
CMF(PO) is the “Classical” CMF 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 27, 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.