## First-Line Chemotherapy for Metastatic Colorectal Cancer **Key Point:** FOLFOX (5-FU + Leucovorin + Oxaliplatin) is the gold-standard first-line chemotherapy regimen for metastatic colorectal cancer (mCRC) in patients with good performance status. ### Rationale for FOLFOX 1. **Superior efficacy**: FOLFOX achieves higher response rates (45–50%) and improved overall survival compared to 5-FU/LV alone. 2. **Doublet backbone**: Combines a fluoropyrimidine (5-FU) with a platinum agent (oxaliplatin), providing synergistic cytotoxicity. 3. **Established standard**: Recommended by ASCO, ESMO, and NCCN as first-line for fit patients. 4. **Biologic add-ons**: Bevacizumab (anti-VEGF) or cetuximab (anti-EGFR, if RAS wild-type) are added to FOLFOX, not used as monotherapy initially. ### Role of Biologic Agents | Agent | Mechanism | Role in mCRC | |-------|-----------|-------------| | **Bevacizumab** | Anti-VEGF monoclonal antibody | Added to FOLFOX/FOLFIRI; improves OS and PFS | | **Cetuximab** | Anti-EGFR monoclonal antibody | Added to chemotherapy if RAS/BRAF wild-type; monotherapy only in rare chemo-refractory cases | | **Panitumumab** | Anti-EGFR monoclonal antibody | Alternative to cetuximab; RAS wild-type selection required | **High-Yield:** FOLFOX is the backbone; biologics are added, not substituted. Monotherapy with any single agent is not standard first-line. **Clinical Pearl:** Patient selection matters — FOLFOX is preferred in fit patients; simplified 5-FU/LV or capecitabine may be used in elderly or frail patients. [cite:Harrison 21e Ch 297]
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