Cisplatin and Cyclophosphamide in Triple-Negative Breast Cancer
For triple-negative breast cancer, cisplatin combined with taxanes (not cyclophosphamide alone) is a guideline-supported regimen, particularly in the neoadjuvant setting where carboplatin (preferred over cisplatin) plus taxanes significantly increases pathologic complete response rates from 37% to 53%. 1
Neoadjuvant Setting (Early Stage TNBC)
The preferred platinum-containing regimen is weekly paclitaxel 80 mg/m² plus carboplatin AUC 2 on days 1,8, and 15 every 28 days, NOT cisplatin with cyclophosphamide. 1 This weekly carboplatin-taxane combination is the NCCN-recommended approach for triple-negative disease. 1
- The standard neoadjuvant protocol includes taxanes, carboplatin, anthracyclines, and cyclophosphamide, ideally combined with concurrent pembrolizumab for stage II/III disease. 2
- Sequential anthracycline-based regimens (such as doxorubicin-cyclophosphamide) followed by taxanes represent an evidence-based alternative. 2
- Adding carboplatin to anthracycline-taxane regimens increases pathologic complete response rates substantially, though ESMO notes this doesn't consistently translate to improved survival outcomes. 1
Metastatic Setting (Stage IV TNBC)
For metastatic disease, albumin-bound paclitaxel plus carboplatin is the superior platinum-containing combination, demonstrating significantly longer progression-free survival and overall survival compared to other regimens. 1
- Platinum agents (carboplatin or cisplatin) with or without taxanes are appropriate first-line options, with selection based on individual risk-benefit assessment. 3
- The TNT trial showed carboplatin and docetaxel had similar overall response rates (31.4% vs 34.0%) in first-line metastatic TNBC. 3
- Patients with germline BRCA1/2 mutations showed significantly better response to carboplatin (68.0% vs 33.3%, p=0.03). 1
Critical Guideline Limitations on Cisplatin-Cyclophosphamide
No robust, prospective randomized data exist supporting platinum compounds in the adjuvant setting for unselected triple-negative tumors, and therefore routine use cannot be recommended. 4 The ESMO 2015 guidelines explicitly state this limitation. 4
- The classic "AC" regimen (doxorubicin-cyclophosphamide) is considered equal to six cycles of CMF, but does not include platinum agents. 4
- Four cycles of docetaxel-cyclophosphamide (TC) may be used as an alternative to anthracycline-based chemotherapy in selected patients at risk of cardiac complications. 4
Alternative Platinum Regimens with Evidence
Research data support cisplatin-containing regimens in specific contexts:
- Cisplatin 60 mg/m² every 3 weeks with weekly paclitaxel for 12 weeks, following dose-dense epirubicin-cyclophosphamide, achieved 48.1% pathologic complete response in locally advanced TNBC. 5
- Dose-dense docetaxel-cyclophosphamide alternating with epirubicin-cisplatin (ddDCEP) achieved 55.2% pathologic complete response with favorable 30-month event-free survival of 91.2%. 6
- However, a randomized trial showed docetaxel-carboplatin alone had superior 5-year disease-free survival (85% vs 64.4%) and overall survival (91.7% vs 81.3%) compared to adding doxorubicin-cyclophosphamide. 7
Essential Testing Requirements
All triple-negative breast cancer patients should undergo germline BRCA1/2 mutation testing to identify candidates for PARP inhibitors and to inform carboplatin benefit. 1, 2
Common Pitfalls to Avoid
- Use carboplatin AUC 2 weekly instead of AUC 6 every 3 weeks when combining with weekly paclitaxel to avoid excessive toxicity. 1
- Cisplatin requires extensive hydration (1-2 liters for 8-12 hours pre-treatment, then diluted in 2 liters over 6-8 hours) and cannot be given by rapid IV injection. 8
- Do not use needles or IV sets containing aluminum with cisplatin, as this causes precipitate formation and loss of potency. 8
- Cyclophosphamide requires adequate fluid administration during or immediately after administration to reduce urinary tract toxicity risk. 9