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.
CMF(PO)
Adjuvant
Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.
Adjuvant therapy for node-positive and high risk node-negative breast cancer patients, in whom an anthracycline and taxane is contraindicated.
Treatment of advanced breast cancer.
cyclophosphamide
ODB - General Benefit
(cyclophosphamide - oral tablets)
(ODB Formulary
)
| cyclophosphamide | 100 mg /m² | PO | Days 1 to 14 |
|
(Outpatient prescription in multiples of 25mg or 50mg tablets)
|
|||
| methotrexate | 40 mg /m² | IV | Days 1 and 8 |
| fluorouracil | 600 mg /m² | IV | Days 1 and 8 |
REPEAT EVERY 28 DAYS
For a usual total of 6 cycles unless disease progression or unacceptable toxicity occurs
Low
Consider prophylaxis daily for cyclophosphamide PO
Other Supportive Care:
Also refer to CCO Antiemetic Recommendations.
Doses should be modified according to the protocol by which the patient is being treated. The following recommendations are in use at some centres.
Patients should be tested for DPD deficiency before starting treatment with fluorouracil. Refer to the DPD Deficiency Guidance for Clinicians for more information.
In patients with unrecognized DPD deficiency, acute, life-threatening toxicity may occur; if grade 2-4 acute toxicity develops, treatment should be stopped immediately and permanent discontinuation considered based on clinical assessment of the toxicities.
Dosage with toxicity
Hematologic Toxicities:
|
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)
|
||
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 ↓ |
Dosage in the Elderly
- No dose modification of cyclphosphamide routinely required, but should be used with caution.
- Methotrexate has not been well studied in the elderly. It should be used with extreme caution because of likely renal and hepatic impairment and reduced folate stores in the elderly. Monitor closely. Consider lower doses with intrathecal usage.
|
Most Common Side Effects |
Less Common Side Effects, but may be |
|
|
Refer to cyclophosphamide, methotrexate, fluorouracil drug monograph(s) for additional details
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Recommended Clinical Monitoring
- CBC; baseline and before each cycle
- Liver function tests; Baseline and before each cycle
- Renal function tests; Baseline and before each cycle
- Urinalysis; Baseline and as clinically indicated
- Clinical assessment and grading of stomatitis, diarrhea, bleeding, infection, GI, pulmonary, CNS, and local site toxicity, skin effects (rash or hand-foot-syndrome), cardiovascular or ophthalmic effects, cystitis, thromboembolism; At each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
- Lung function tests if pulmonary toxicity suspected;
- CXR; Baseline
- Hepatitis B and Hepatitis C infection testing; Baseline
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Bonadonna G, Moliterni A, Zambetti M, et al. 30 years' follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study. BMJ doi:10.1136/bmj.38314.622095.8F (published 13 January 2005).
Cyclophosphamide, methotrexate, fluorouracil, trastuzumab drug monographs, Cancer Care Ontario.
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.
Fisher B, Brown AM, Dimitrov NV, et al. Two months of Doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of Cyclophosphamide, Methotrexate, and 5-Fluorouracil in positive-breast cancer patients with tamoxifen-nonresponsive tumors: results from the NSABP B-15, J. Clin Oncol 1990 Sep:8(9): 1483-1496.
April 2023 Updated DPD deficiency information in the Dose Modifications section
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.
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