## Treatment of Locally Advanced Laryngeal Carcinoma ### Neoadjuvant Chemotherapy Regimen **Key Point:** Cisplatin with 5-fluorouracil (5-FU) is the gold-standard neoadjuvant chemotherapy regimen for locally advanced squamous cell carcinoma of the larynx, as established by the RTOG and EORTC protocols. ### Mechanism and Rationale 1. **Cisplatin** — platinum-based alkylating agent; induces DNA cross-links and is the backbone of head and neck cancer chemotherapy 2. **5-Fluorouracil** — antimetabolite; inhibits thymidylate synthase and enhances cisplatin efficacy through synergistic action ### Evidence Base **High-Yield:** The VAC regimen (Vinblastine, Actinomycin D, Cyclophosphamide) and later CF (Cisplatin-5FU) protocols demonstrated improved overall survival and laryngeal preservation when combined with concurrent radiation therapy in locally advanced disease [cite:Harrison 21e Ch 81]. ### Typical Dosing Schedule | Component | Dose | Frequency | |-----------|------|----------| | Cisplatin | 75–100 mg/m² | Day 1, every 3–4 weeks | | 5-Fluorouracil | 1000 mg/m²/day | Days 1–5 continuous infusion | | Cycles | 2–3 cycles | Pre-radiation | ### Clinical Pearl Neoadjuvant chemotherapy followed by concurrent chemoradiation or radiation alone offers laryngeal preservation in 60–70% of patients with T3–T4 disease, avoiding total laryngectomy in selected cases. ### Monitoring and Toxicity **Warning:** Cisplatin causes nephrotoxicity, ototoxicity, and neuropathy; requires aggressive hydration and electrolyte monitoring. 5-FU causes mucositis and myelosuppression.
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