## Adjuvant Chemotherapy in Locally Advanced Gastric Cancer (T3N2M0) **Key Point:** For resected locally advanced gastric cancer (stage III) after D2 lymphadenectomy, **Capecitabine + Oxaliplatin (CAPOX/CapeOx)** is the current standard adjuvant regimen, supported by the CLASSIC trial and endorsed by NCCN, ESMO, and JGCA guidelines. ### Rationale for Capecitabine + Oxaliplatin **High-Yield:** The **CLASSIC trial (2012)** — a landmark phase III RCT — randomized 1,035 patients with stage II–IIIB gastric cancer after D2 gastrectomy to adjuvant CAPOX vs. observation: - **3-year DFS:** 74% (CAPOX) vs. 59% (observation); HR 0.56, p<0.0001 - **5-year OS:** 78% (CAPOX) vs. 69% (observation); HR 0.66, p=0.0015 - **Conclusion:** CAPOX significantly improved both DFS and OS after D2 resection This is the **highest-level evidence** specifically for the post-D2 lymphadenectomy adjuvant setting, which matches this patient's surgical procedure exactly. ### Why CAPOX Over 5-FU + Cisplatin? | Feature | CAPOX | 5-FU + Cisplatin | |---------|-------|-----------------| | Trial evidence (post-D2) | CLASSIC (RCT, n=1035) | No dedicated RCT post-D2 | | Toxicity | Better tolerated | Nephrotoxicity, emetogenicity | | Administration | Oral capecitabine + IV oxaliplatin | IV infusion (5-FU) + IV cisplatin | | Guideline endorsement | NCCN Category 1, ESMO | Less preferred in current guidelines | **5-FU + Cisplatin** lacks a dedicated phase III RCT in the post-D2 adjuvant setting. The MAGIC trial used perioperative ECF (epirubicin + cisplatin + 5-FU), not adjuvant 5-FU + cisplatin alone, and was conducted predominantly in Western patients with D0/D1 resections. ### ACTS-GC Trial (S-1 Adjuvant Therapy) - **S-1** (oral fluoropyrimidine, tegafur/gimeracil/oteracil) is the standard in Japan after D2 resection (ACTS-GC trial, HR 0.68 for OS) - S-1 is not widely available outside Japan/Korea; **CAPOX is the internationally applicable equivalent** with the strongest RCT evidence ### Why Not the Other Options? - **Option A (5-FU + Cisplatin):** No phase III RCT supports this specific doublet as adjuvant therapy post-D2 gastrectomy; cisplatin's nephrotoxicity and emetogenicity make it less preferred when CAPOX has superior evidence - **Option B (DCF — Docetaxel + 5-FU + Cisplatin):** A palliative/metastatic regimen (TAX325 trial); not a standard adjuvant regimen; excessive toxicity without proven adjuvant benefit - **Option D (Ramucirumab monotherapy):** Anti-VEGFR2 antibody approved for metastatic gastric cancer (REGARD trial); no role in adjuvant setting ### HER2 Status The tumor is **HER2-negative** → Trastuzumab is not indicated. Pertuzumab/trastuzumab combinations are under investigation in HER2-positive adjuvant settings (APHINITY-like trials). **Clinical Pearl:** Per NCCN Guidelines v2024 and ESMO 2022, **CAPOX (Capecitabine + Oxaliplatin)** is a Category 1 recommendation for adjuvant chemotherapy in resected gastric cancer after D2 lymphadenectomy, based on the CLASSIC trial. This is the drug of choice for this HER2-negative, stage IIIB patient. *Reference: Bang YJ et al. CLASSIC trial. Lancet 2012; 379:315–321. NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer, v2.2024.*
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