A 58-year-old man from rural India presents with progressive dysphagia and epigastric pain for 4 months. Upper endoscopy reveals a large ulcerated mass in the gastric antrum. Biopsy confirms adenocarcinoma. CT staging shows locally advanced disease (T3N2M0). He is deemed fit for neoadjuvant chemotherapy followed by surgery. What is the drug of choice for neoadjuvant treatment of locally advanced gastric cancer?

Explanation

## Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer ### Standard Regimen **Key Point:** The DCF regimen (Docetaxel + Cisplatin + 5-Fluorouracil) is the gold-standard neoadjuvant chemotherapy for locally advanced gastric cancer (T3–T4 or node-positive disease). ### Evidence Base **High-Yield:** The MAGIC trial (2006) and subsequent FLOT studies established that perioperative chemotherapy improves overall survival in resectable gastric cancer. The DCF regimen offers superior response rates (37–48%) compared to CF alone. ### Mechanism of Action - **5-Fluorouracil:** Antimetabolite; inhibits thymidylate synthase and DNA synthesis - **Cisplatin:** Alkylating agent; cross-links DNA, induces apoptosis - **Docetaxel:** Microtubule stabilizer; arrests mitosis ### Clinical Application | Aspect | Detail | |--------|--------| | **Indication** | T3–T4, node-positive, or locally advanced gastric adenocarcinoma | | **Timing** | Neoadjuvant (pre-operative) or perioperative | | **Cycles** | Usually 3 pre-op + 3 post-op | | **Response Rate** | 37–48% (pathological CR ~15%) | | **Survival Benefit** | ~5-year OS improvement of 10–15% | **Clinical Pearl:** FLOT (5-FU + Leucovorin + Oxaliplatin + Docetaxel) is an emerging alternative with potentially better tolerability, but DCF remains the most widely used and guideline-recommended regimen globally. **Warning:** Trastuzumab is reserved for HER2-positive tumors (confirmed by IHC 3+ or FISH+); it is not first-line monotherapy and requires HER2 testing. Imatinib is used only in rare GIST (gastrointestinal stromal tumors), not adenocarcinoma.