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regimen-monograph

A - Regimen Name

FAC Regimen
Fluorouracil-ADRIAMYCIN ® (DOXOrubicin)-Cyclophosphamide


Disease Site
Breast

Intent
Palliative

Regimen Category
Evidence-Informed :

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.


Rationale and Uses

Treatment of advanced breast cancer

 
B - Drug Regimen

fluorouracil

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

(Round to nearest 1 mg)
50 mg /m² IV Day 1
cyclophosphamide

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

 

 

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C - Cycle Frequency

REPEAT EVERY 21 DAYS

Until evidence of non-response, disease progression or limited by cardiotoxicity risk

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

High

Other Supportive Care:

Also refer to CCO Antiemetic Recommendations.

 
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.



Hepatic Impairment

Bilirubin Action
1-2 x ULN REDUCE Doxorubicin to 50% dose
>2-4 x ULN REDUCE Doxorubicin to 25% dose
>4 x ULN STOP treatment with Doxorubicin and Fluorouracil

Renal Impairment

Fluorouracil:  No adjustment required, although reduction may be considered with severe renal insufficiency.

Doxorubicin:   No adjustment required.

Cyclophosphamide:  Renal failure may lead to the reduced excretion of metabolites and increased toxicity.  Significant falls in clearance (25-80%) with increased exposure have been documented in patients with renal impairment.  Dose reduction (25- 50%) should be considered in patients with mild to moderate renal impairment. Patients with moderate renal impairment receiving high doses or severe renally impaired patients (CrCl < 10 mL/min) are at particular risk and should be treated at a reduced dose and with extreme caution.

 
F - Adverse Effects
Refer to cyclophosphamide, DOXOrubicin, 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
  • Alopecia
  • Vesicant
 
G - Interactions
Refer to fluorouracil, DOXOrubicin, cyclophosphamide drug monograph(s) for additional details
 
H - Drug Administration and Special Precautions
Refer to fluorouracil, DOXOrubicin, cyclophosphamide drug monograph(s) for additional details
 
I - Recommended Clinical Monitoring

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

  • Clinical toxicity assessment (including stomatitis, cardiotoxicity, local toxicity, cystitis); at each visit
  • CBC; baseline and before each cycle
  • Baseline and regular liver and renal function tests
  • Cardiac examination especially with risk factors (including prior therapy with Epirubicin, Mitoxantrone, or other cardiotoxic drug), or a cumulative doxorubicin dose of > 450 mg/m2
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


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J - Administrative Information

Approximate Patient Visit
1.5 hour
Pharmacy Workload (average time per visit)
24.6 minutes
Nursing Workload (average time per visit)
41.667 minutes
 
K - References

Bull JM, Tormey DC, et al, A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy. Cancer, 1978; 41: 1649-1657

Italian Multicentre Breast Study with Epirubicin.  Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: An Italian multicentre trial. J Clin Oncol, 1988; 6: 976-982

Calabresi F, Di Lauro L, et al, Fluorouracil, doxorubicin, and cyclophosphamide versus fluorouracil, doxorubicin, and cyclophosphamide plus lonidamine for the treatment of advanced breast cancer: A multicentric randomized clinical study. Sem Oncol, 1991; 18 (Suppl 4): 68-72

Nabholtz JA, Paterson A, Dirix J et al.  A phase III randomized trial comparing docetaxel (T), doxorubicin (A) and cyclophosphamide (C) (TAC) to FAC as first line chemotherapy (CT) for patients with metastatic beast cancer (MBC).  Proceedings ASCO 2001: Abstract #83.

Swenerton KD, Legha SS, Smith T, et al.  Prognostic Factors in Metastatic breast cancer treated with combination chemotherapy.  Cancer Research 1979; May  39:  1552-1562

Hortobagyi GN, Gutterman JU, Blumenschein GR, et al.  Combination chemoimmunotherapy of metastatic breast cancer with 5-fluorouracil, adriamycin, cyclophosphamide, and BCG.  Cancer 1979; 43:  1225-1233.

June 2019 Updated emetic risk category


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L - Other Notes

If Cyclophosphamide given PO, see regimen CAF

 
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.
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Last Updated: July 27, 2026