bevacizumab + carboplatin + cyclophosphamide + doxorubicin + paclitaxel

This drug combination is a multi-agent chemotherapy regimen primarily used in the treatment of triple-negative breast cancer (TNBC). It was studied in the CALGB 40603 (Alliance) clinical trial, a randomized phase II trial evaluating the impact of adding carboplatin and/or bevacizumab to standard neoadjuvant chemotherapy. **Regimen Components:** * **Bevacizumab (Avastin)**: A monoclonal antibody that targets vascular endothelial growth factor (VEGF), inhibiting angiogenesis. * **Carboplatin**: A platinum-based chemotherapy agent that forms DNA crosslinks, inhibiting DNA synthesis. * **Cyclophosphamide**: An alkylating agent that damages DNA and prevents cancer cell division. * **Doxorubicin**: An anthracycline antibiotic that intercalates DNA and inhibits topoisomerase II. * **Paclitaxel**: A taxane that stabilizes microtubules, preventing cell division. **Administration Protocol (CALGB 40603 trial):** * Paclitaxel 80 mg/m² once weekly for 12 weeks * Doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m² once every 2 weeks for 4 cycles (ddAC) * Carboplatin (area under curve 6) once every 3 weeks for 4 cycles * Bevacizumab 10 mg/kg once every 2 weeks for 9 cycles **Clinical Efficacy:** The addition of carboplatin and/or bevacizumab to standard neoadjuvant chemotherapy significantly increased pathologic complete response (pCR) rates in patients with TNBC. Specifically: * Addition of carboplatin increased pCR in breast from 44% to 60% (p=0.0018). * Addition of bevacizumab increased pCR in breast from 48% to 59% (p=0.0089). * Only carboplatin significantly increased pCR in both breast and axilla (54% vs 41%, p=0.0029). **Toxicity Profile:** Patients assigned to either carboplatin or bevacizumab experienced more toxicities. Both agents reduced the likelihood of completing therapy without dose modifications or early discontinuation. * Carboplatin was associated with increased grade ≥3 neutropenia and thrombocytopenia. * Bevacizumab was associated with increased hypertension, infection, thromboembolic events, bleeding, and postoperative complications.