A 58-year-old man from rural India presents with progressive dysphagia and epigastric pain for 4 months. Upper endoscopy reveals a large ulcerating mass in the gastric antrum with biopsy-confirmed adenocarcinoma. CT staging shows locally advanced disease (T3N2M0). He is deemed fit for neoadjuvant chemotherapy followed by gastrectomy. What is the preferred chemotherapy regimen for locally advanced gastric cancer?

Explanation

## Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer ### Standard Regimen **Key Point:** DCF (Docetaxel + Cisplatin + 5-Fluorouracil) is the gold-standard neoadjuvant chemotherapy regimen for locally advanced gastric cancer (T3–T4 or node-positive disease) [cite:Harrison 21e Ch 297]. ### Evidence Base **High-Yield:** The V-325 trial and subsequent meta-analyses demonstrated that triplet chemotherapy (DCF) improves overall survival and R0 resection rates compared to doublet regimens in locally advanced gastric cancer. - **Mechanism of synergy:** Docetaxel (microtubule stabilizer) + Cisplatin (platinum cross-linker) + 5-FU (antimetabolite) target multiple pathways. - **Typical dosing:** Docetaxel 75 mg/m², Cisplatin 75 mg/m², 5-FU 750 mg/m²/day × 5 days, repeated every 28 days for 2–3 cycles preoperatively. ### Alternative Regimens | Regimen | Use Case | Rationale | |---------|----------|----------| | **DCF (triplet)** | Locally advanced, fit patients | Best survival benefit; standard of care | | **ECF** (Epirubicin/Cisplatin/5-FU) | Alternative triplet | Similar efficacy, slightly different toxicity profile | | **Cisplatin + Capecitabine** | Doublet option | Used when DCF toxicity is a concern | | **Monotherapy (5-FU or Capecitabine)** | Palliative or unfit patients | Insufficient for curative-intent locally advanced disease | ### Clinical Pearl **Clinical Pearl:** Neoadjuvant chemotherapy improves R0 resection rates and pathological response in locally advanced gastric cancer, translating to better overall survival compared to surgery alone [cite:Robbins 10e Ch 7]. ### Why DCF Over Doublets? 1. **Superior pathological complete response (pCR):** ~25–30% with DCF vs. ~15% with doublets. 2. **Better overall survival:** Median OS ~36 months with DCF vs. ~28 months with surgery alone. 3. **Acceptable toxicity:** Grade 3–4 neutropenia and diarrhea are manageable with supportive care.