## First-Line Adjuvant Chemotherapy for Stage III CRC **Key Point:** FOLFOX (5-FU + Leucovorin + Oxaliplatin) is the gold-standard first-line adjuvant regimen for stage III colorectal carcinoma and is superior to 5-FU/LV alone [cite:Harrison 21e Ch 297]. ### Mechanism of Action | Drug | MOA | Role | |------|-----|------| | 5-Fluorouracil | Thymidylate synthase inhibitor; disrupts DNA/RNA synthesis | Backbone agent | | Leucovorin (Folinic acid) | Potentiates 5-FU by stabilizing ternary complex | Synergist | | Oxaliplatin | DNA cross-linking platinum agent | Adds efficacy; improves OS | **High-Yield:** FOLFOX improves overall survival and disease-free survival compared to 5-FU/LV monotherapy in stage III CRC. The addition of oxaliplatin reduces recurrence risk by ~20% [cite:Robbins 10e Ch 17]. ### Regimen Specifics 1. Oxaliplatin 85 mg/m² IV on day 1 2. Leucovorin 400 mg/m² IV on day 1 3. 5-FU 400 mg/m² IV bolus + 2400 mg/m² 46-hour infusion 4. Repeat every 2 weeks for 12 cycles (6 months) **Clinical Pearl:** Oxaliplatin causes cumulative peripheral neuropathy (dose-limiting toxicity). Baseline neuropathy assessment and patient counseling are essential before starting. **Warning:** Do NOT use monotherapy with 5-FU or capecitabine alone in stage III disease — this is suboptimal and increases recurrence risk.
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