Weekly Paclitaxel and Carboplatin Protocol for Triple-Negative Breast Cancer
For triple-negative breast cancer, the recommended weekly protocol is paclitaxel 80 mg/m² IV on days 1,8, and 15 plus carboplatin AUC 2 IV on days 1,8, and 15, cycled every 28 days. 1
Standard Dosing Regimens
Weekly Schedule (Preferred for Neoadjuvant Setting)
- Paclitaxel: 80 mg/m² IV infusion on days 1,8, and 15 1
- Carboplatin: AUC 2 IV on days 1,8, and 15 1
- Cycle length: 28 days 1
- Duration: Typically 12 weeks (3-4 cycles) in neoadjuvant setting, followed by anthracycline-based therapy 2, 3
Alternative Every-3-Week Schedule
Clinical Context and Evidence
The weekly dosing schedule achieves comparable pathologic complete response rates (50-60%) to every-3-week dosing while maintaining excellent treatment completion rates. 4, 2, 5 The CALGB 40603 trial demonstrated that adding carboplatin to weekly paclitaxel significantly increased pCR rates from 41% to 54% in stage II-III triple-negative breast cancer 2. A retrospective analysis confirmed that 83% of patients receiving weekly carboplatin completed at least 11 of 12 planned doses, with pCR rates of 53% for weekly versus 55% for every-3-week dosing 5.
Treatment Sequence in Neoadjuvant Setting
- Phase 1: Weekly paclitaxel + carboplatin for 12 weeks 2, 3
- Phase 2: Dose-dense doxorubicin 60 mg/m² + cyclophosphamide 600 mg/m² every 2-3 weeks for 4 cycles 2, 3
- Alternative anthracycline: Epirubicin 90 mg/m² + cyclophosphamide 600 mg/m² every 3 weeks for 4 cycles 3
Expected Toxicities and Management
Hematologic Toxicities (Most Common)
- Grade ≥3 neutropenia: 25-96% of patients 1, 2, 3
- Grade ≥3 thrombocytopenia: 15-18% of patients 2, 3
- Grade ≥3 anemia: 40% of patients 3
- Neutropenic fever: 22% of patients 3
Non-Hematologic Toxicities
- Liver function test abnormalities: 6.8% grade 3 4
- Diarrhea and fatigue: 4.5% grade 3 each 4
- Peripheral neuropathy: Monitor closely, dose modifications may be required 1
Critical Treatment Delivery Considerations
Patients assigned to carboplatin are less likely to complete all planned doses without modification (approximately 83-90% completion rate), but this does not significantly compromise pCR rates. 2, 5 The weekly schedule may offer better tolerability compared to every-3-week dosing, though both achieve similar efficacy outcomes 5.
Dose Modification Algorithm
- For grade 4 neutropenia or grade 3 thrombocytopenia: Hold treatment until recovery to grade ≤2, then resume with myeloid growth factor support 3
- For grade ≥3 peripheral neuropathy: Reduce paclitaxel dose by 20% or hold until improvement to grade ≤1 1
- For persistent toxicity: Consider switching from weekly to every-3-week carboplatin dosing 5
Metastatic Setting Considerations
For first-line metastatic triple-negative breast cancer, nab-paclitaxel 100 mg/m² plus carboplatin AUC 2 on days 1,8,15 every 28 days demonstrates superior outcomes with median PFS of 9.2 months and ORR of 85%. 6 This regimen can be combined with bevacizumab 10 mg/kg on days 1 and 15 for PD-L1-positive disease, though bevacizumab adds hypertension (13.6%) and bleeding (27%) risks 4, 6.
Alternative First-Line Options
- PD-L1-positive disease: Consider atezolizumab plus nab-paclitaxel or pembrolizumab plus chemotherapy for superior overall survival 7, 8
- BRCA-mutated disease: PARP inhibitors (olaparib or talazoparib) are preferred over chemotherapy after prior treatment 9, 7, 8
- After ≥2 prior therapies: Sacituzumab govitecan demonstrates dramatic superiority (ORR 35% vs 5%) over standard chemotherapy 9, 7, 8
Common Pitfalls to Avoid
- Do not administer carboplatin every 3 weeks at AUC 6 when using weekly paclitaxel - this creates excessive toxicity; use AUC 2 weekly instead 1
- Do not skip myeloid growth factor support when using dose-dense anthracycline regimens following paclitaxel-carboplatin 2, 3
- Do not delay genetic testing - all triple-negative breast cancer patients should undergo germline BRCA1/2 testing to identify PARP inhibitor candidates 7, 8
- Do not assume weekly dosing is inferior - completion rates and pCR rates are equivalent between weekly and every-3-week carboplatin schedules 5