Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.

regimen-monograph

A - Regimen Name

CMF Regimen
Cyclophosphamide-Methotrexate-Fluorouracil


Disease Site
Breast

Intent
Palliative

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
Treatment of advanced breast cancer
 
B - Drug Regimen

cyclophosphamide

(Round to nearest 10mg)
600 mg /m² IV Day 1
methotrexate

(Round to nearest 5mg)
40 mg /m² IV Day 1
fluorouracil

(Round to nearest 25mg)
600 mg /m² IV Day 1

 

 

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C - Cycle Frequency

REPEAT EVERY 21 DAYS

Until non-response or disease progression

 
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% *

 

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

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% OMIT Consider dose ↓
<10 50% or OMIT OMIT Consider dose ↓

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

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


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J - Administrative Information

Approximate Patient Visit
1 hour
 
K - References

Engelsman E, Klijn JCM, et al, “Classical” CMF vs. a 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer. Eur J Cancer, 1991; 27: 966-970.

Ingle JN, Foley JF, et al, Randomized trial of cyclophosphamide, methotrexate, and fluorouracil with or without estrogenic recruitment in women with advanced breast cancer.  Cancer, 1994; 73: 2337-2343.
 
Tannock IF, Boyd NF, et al, A randomized trial of two dose levels of cyclophosphamide, methotrexate, and fluorouracil chemotherapy for patients with metastatic breast cancer.  J Clin Oncol, 1988; 6: 1377-1387.

October 2017 Updated antiemetic classification


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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