CMF Regimen Dosing for Breast Cancer
The classic CMF regimen consists of oral cyclophosphamide 100 mg/m² days 1-14, intravenous methotrexate 40 mg/m² days 1 and 8, and intravenous fluorouracil 600 mg/m² days 1 and 8, repeated every 28 days for six cycles. 1
Primary Dosing Schedule
The ASCO guidelines explicitly designate the classic CMF schedule as the default adjuvant regimen for breast cancer when anthracycline-taxane therapy is contraindicated 1:
- Cyclophosphamide: 100 mg/m² orally, days 1-14 1
- Methotrexate: 40 mg/m² IV, days 1 and 8 1
- Fluorouracil (5-FU): 600 mg/m² IV, days 1 and 8 1
- Cycle length: Every 28 days 1
- Total duration: Six cycles 1
Alternative All-IV Schedule
ASCO recognizes an all-intravenous CMF regimen administered every 21 days is commonly used in clinical practice based on convenience and tolerability, though it lacks efficacy data from randomized controlled trials 1. This schedule was accepted in trials like TAILORx 1.
Critical caveat: The classic oral cyclophosphamide schedule (days 1-14) has superior evidence supporting its efficacy compared to modified schedules 2, 3. Studies demonstrate that reducing dose or altering the CMF schedule compromises efficacy in both metastatic and adjuvant settings 2, 3.
Clinical Context and Indications
CMF is recommended as an acceptable alternative to doxorubicin-cyclophosphamide specifically when anthracycline-taxane regimens are contraindicated 1. The NCCN also lists CMF as a preferred chemotherapy combination for breast cancer treatment 1.
Important distinction: Not all CMF regimens are equivalent 2. The classic schedule with oral cyclophosphamide days 1-14 demonstrated significant benefit when added to tamoxifen in postmenopausal women with estrogen receptor-positive tumors, while modified CMF schedules failed to show this benefit 2, 3.
Dose Density Considerations
Research suggests dose density matters significantly for CMF efficacy 4. A study comparing two intravenous CMF modifications found that the regimen administered on days 1 and 8 every 28 days (30% higher dose density) achieved superior 5-year overall survival (87.5% vs 84%) and 10-year overall survival (82% vs 61.5%) compared to administration only on day 1 every 21 days 4.
Administration Guidelines
- Methotrexate and fluorouracil are administered intravenously on the same days (days 1 and 8) 1
- Cyclophosphamide in the classic regimen is taken orally daily for the first 14 days of each 28-day cycle 1
- Each complete treatment course consists of six 28-day cycles 1
Adherence to the classic dose and schedule is strongly recommended when CMF is used in adjuvant therapy, as deviations have consistently shown inferior outcomes 2, 3.