A 62-year-old man with stage III squamous cell carcinoma of the larynx (T3 N1 M0) is deemed a candidate for concurrent chemoradiation therapy (CCRT). Which chemotherapy agent is the preferred radiosensitizer to be administered weekly during radiation?

Explanation

## Concurrent Chemoradiation for Laryngeal Carcinoma ### First-Line Radiosensitizer Agent **Key Point:** Cisplatin 40 mg/m² administered weekly during concurrent chemoradiation (CCRT) is the gold-standard radiosensitizer for locally advanced laryngeal squamous cell carcinoma, based on landmark RTOG and EORTC trials. ### Mechanism of Radiosensitization 1. **DNA damage potentiation** — cisplatin creates platinum-DNA adducts that prevent repair of radiation-induced DNA breaks 2. **Cell cycle synchronization** — cisplatin arrests cells in G2/M phase, the most radiosensitive phase 3. **Hypoxia reduction** — improved tumor oxygenation enhances radiation efficacy ### Dosing and Administration | Parameter | Details | |-----------|----------| | Cisplatin dose | 40 mg/m² IV weekly | | Total duration | 6–7 weeks (concurrent with RT) | | Radiation dose | 70 Gy in 35 fractions over 7 weeks | | Hydration | Mandatory pre- and post-infusion | ### Evidence Base **High-Yield:** Multiple randomized trials (RTOG 91-11, EORTC 24891) demonstrated that concurrent cisplatin-based chemoradiation improves locoregional control and overall survival compared to radiation alone in T3–T4 laryngeal cancers, with laryngeal preservation rates of 60–70% [cite:Harrison 21e Ch 81]. ### Clinical Pearl Weekly cisplatin dosing (40 mg/m²) is preferred over high-dose cisplatin (75–100 mg/m² every 3 weeks) during CCRT because it provides better tolerability while maintaining radiosensitization efficacy, reducing treatment breaks due to toxicity. ### Toxicity Profile **Warning:** Acute toxicities include severe mucositis, dysphagia, dermatitis, and myelosuppression. Late toxicities include xerostomia, laryngeal edema, and fibrosis. Cisplatin nephrotoxicity and ototoxicity require monitoring.