A 52-year-old man from Delhi presents with a 3-month history of progressive dysphagia and weight loss. Endoscopy reveals a moderately differentiated squamous cell carcinoma of the mid-oesophagus with invasion into the muscularis propria. CT staging shows no distant metastases. What is the drug of choice for neoadjuvant chemotherapy in this locally advanced oesophageal cancer?

## Neoadjuvant Chemotherapy for Locally Advanced Oesophageal Cancer **Key Point:** Cisplatin + 5-FU is the gold-standard regimen for neoadjuvant chemotherapy in locally advanced oesophageal squamous cell carcinoma (SCC), particularly when combined with concurrent radiotherapy (Chemoradiation). **Mechanism of Action:** - **Cisplatin**: Platinum-based alkylating agent; cross-links DNA; radiosensitizer - **5-FU**: Antimetabolite; inhibits thymidylate synthase; enhances radiation effect **Clinical Evidence:** - CROSS trial and subsequent meta-analyses support cisplatin + 5-FU + radiotherapy as standard neoadjuvant approach - Improves overall survival and R0 resection rates in locally advanced oesophageal SCC - Typical regimen: Cisplatin 75 mg/m² on day 1 + 5-FU 1000 mg/m²/day continuous infusion days 1–4, repeated every 28 days × 2–3 cycles concurrent with 50 Gy radiotherapy **High-Yield:** This combination is preferred over taxane-based regimens in SCC of the oesophagus; taxanes are more commonly used in adenocarcinoma of the gastro-oesophageal junction.