4-Week Interval for Docetaxel, Cyclophosphamide, and Doxorubicin
Yes, a 4-week (every 3 weeks) interval is the standard and effective dosing schedule for the docetaxel-doxorubicin-cyclophosphamide (TAC) regimen, administered for 6 cycles with mandatory G-CSF support. 1, 2
Standard Dosing Schedule
The TAC regimen consists of docetaxel 75 mg/m², doxorubicin 50 mg/m², and cyclophosphamide 600 mg/m² administered intravenously every 3 weeks (21-day cycles) for 6 cycles. 1, 2
- This every-3-week schedule with mandatory filgrastim (G-CSF) support is non-negotiable due to significant hematologic toxicity 2
- The regimen has demonstrated superiority over fluorouracil-doxorubicin-cyclophosphamide × 6 in clinical trials 1
Guideline-Supported Evidence
The 2018 ASCO guidelines explicitly list docetaxel-doxorubicin-cyclophosphamide × 6 as one of the recommended adjuvant chemotherapy regimens for early breast cancer, particularly for high-risk patients 1. This regimen:
- Holds Category 1 recommendation status for HER2-negative disease in the adjuvant setting 2
- Is classified as a "preferred" regimen by NCCN guidelines, though it has been somewhat superseded by dose-dense AC followed by taxane regimens in more recent guidelines 2
Alternative Dosing Considerations
If you are considering the two-drug docetaxel-cyclophosphamide (TC) regimen instead, the standard is 4 cycles every 3 weeks, not 6 cycles. 1, 3
- TC consists of docetaxel 75 mg/m² and cyclophosphamide 600 mg/m² every 21 days for 4 cycles 3
- TC × 4 is recommended as an alternative to AC × 4 and offers improved disease-free survival and overall survival 1, 3
- At 7-year follow-up, TC demonstrated superior DFS (81% vs 75%, P=0.033) and OS (87% vs 82%, P=0.032) compared to AC 4
Sequential Regimens vs. Concurrent TAC
Sequential regimens (AC × 4 followed by docetaxel × 4) are also administered every 3 weeks and are superior to AC alone. 1
- Doxorubicin-cyclophosphamide × 4 → docetaxel × 4 is explicitly listed as superior to doxorubicin-cyclophosphamide × 4 alone 1
- Sequential administration of docetaxel followed by AC has been shown feasible with favorable toxicity profiles in clinical trials 5, 6
Critical Safety Considerations
- Mandatory G-CSF support is required with TAC due to significant hematologic toxicity 2
- Grade 3/4 neutropenia occurs in 63.3% of patients with TAC regimens 1
- Febrile neutropenia occurs in approximately 9.3% of patients despite G-CSF support 1
- Monitor for anthracycline-related cardiac toxicity (LVEF monitoring required) 2
- The cumulative dose of doxorubicin should not exceed 240 mg/m² in two-drug regimens 1
Clinical Pitfalls to Avoid
Do not attempt to extend the TAC regimen to a 4-week (28-day) cycle interval - the evidence base and guideline recommendations are specifically for every-3-week administration 1, 2. Altering the interval would deviate from the studied and approved regimen without supporting evidence for efficacy or safety.