A 65-year-old male with stage IIB squamous cell carcinoma of the larynx (T2N1M0) is deemed suitable for organ preservation. After completing induction chemotherapy with cisplatin and 5-FU, he is to receive concurrent chemoradiation. What is the drug of choice for concurrent chemotherapy during radiotherapy?

Explanation

## Concurrent Chemoradiation for Laryngeal Carcinoma **Key Point:** Weekly cisplatin is the preferred concurrent chemotherapy agent during radiotherapy for locally advanced laryngeal carcinoma, following induction chemotherapy in the organ-preservation paradigm. ### Rationale for Concurrent Cisplatin **High-Yield:** The RTOG 91-11 trial demonstrated that induction cisplatin + 5-FU followed by concurrent chemoradiation (with weekly cisplatin 40 mg/m²) achieved superior laryngeal preservation and overall survival compared to radiation alone or concurrent chemoradiation without induction. **Clinical Pearl:** Concurrent chemoradiation acts as a radiosensitizer, enhancing tumor cell kill while maintaining acceptable toxicity. Weekly low-dose cisplatin (40 mg/m²) is preferred over high-dose cisplatin during radiation due to reduced cumulative toxicity while maintaining efficacy. ### Concurrent Chemoradiation Regimen | Parameter | Details | |-----------|----------| | **Chemotherapy Agent** | Cisplatin 40 mg/m² IV weekly | | **Timing** | Given on day 1 of each radiation week | | **Duration** | 6–7 weeks (concurrent with RT) | | **Radiation Dose** | 70 Gy in conventional fractionation (2 Gy/day) | | **Radiosensitization Mechanism** | Cisplatin inhibits DNA repair, enhances RT-induced apoptosis | **Warning:** Concurrent chemoradiation carries significant acute toxicity — mucositis, dysphagia, dermatitis, and hematologic suppression are common. Nutritional support (PEG tube consideration) and close monitoring are essential. ### Treatment Timeline: Induction → Concurrent CRT ```mermaid flowchart TD A[Locally Advanced Laryngeal SCC]:::outcome --> B[Induction: Cisplatin + 5-FU × 3 cycles]:::action B --> C{Response Assessment}:::decision C -->|CR/PR| D[Concurrent Chemoradiation]:::action D --> E[Weekly Cisplatin 40 mg/m²]:::action E --> F[Radiation 70 Gy/7 weeks]:::action F --> G{Laryngeal Preservation Achieved?}:::decision G -->|Yes| H[Long-term Follow-up]:::outcome G -->|No| I[Salvage Total Laryngectomy]:::action ``` **Mnemonic:** **W-CIS** = **W**eekly **CIS**platin during concurrent chemoradiation (lower dose, better tolerance than high-dose cisplatin). ### Dosing and Administration - **Cisplatin:** 40 mg/m² IV weekly (days 1, 8, 15, 22, 29, 36, 43 of radiation) - **Hydration:** Aggressive IV hydration pre- and post-cisplatin - **Monitoring:** Weekly CBC, renal function, audiometry baseline and post-treatment **Tip:** If cisplatin is contraindicated (renal impairment, hearing loss), cetuximab weekly is an alternative, though it is less effective than cisplatin-based CRT. [cite:Harrison 21e Ch 97; RTOG 91-11 Trial]