## Adjuvant Chemotherapy for Stage III Colorectal Cancer **Key Point:** The standard adjuvant regimen for stage III colorectal cancer is 5-FU/leucovorin combined with oxaliplatin (FOLFOX or CAPEOX regimen). ### Rationale for FOLFOX **High-Yield:** FOLFOX (5-FU + leucovorin + oxaliplatin) is the gold-standard adjuvant therapy for stage III colorectal cancer, demonstrated to improve disease-free survival (DFS) and overall survival (OS) compared to 5-FU/leucovorin alone in landmark trials (MOSAIC, NSABP C-07). ### Mechanism of Action | Drug | Class | Mechanism | |------|-------|----------| | 5-Fluorouracil | Antimetabolite | Inhibits thymidylate synthase; disrupts DNA/RNA synthesis | | Leucovorin | Folate analog | Enhances 5-FU efficacy by stabilizing ternary complex | | Oxaliplatin | Platinum agent | Forms DNA cross-links; synergistic with 5-FU | ### Treatment Duration **Clinical Pearl:** Adjuvant FOLFOX is typically administered for 6 months (12 cycles) in stage III disease. The addition of oxaliplatin to 5-FU/LV reduces recurrence risk by ~20% compared to 5-FU/LV alone. ### Patient Selection - **Stage III (any T, N1–N2, M0):** FOLFOX is standard of care. - **High-risk stage II:** May be considered in selected cases (poor differentiation, T4, <12 nodes examined, MSI-stable). - **Contraindication:** Severe peripheral neuropathy (oxaliplatin is neurotoxic); consider 5-FU/LV alone in such cases. **Warning:** Do not confuse adjuvant (post-operative) with neoadjuvant (pre-operative) therapy. Neoadjuvant chemoradiation is used for locally advanced rectal cancer (T3–T4 or N+), not colon cancer.
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