A 58-year-old male smoker presents with hoarseness of voice for 3 months. Laryngoscopy reveals a 2 cm exophytic lesion on the left vocal cord with no evidence of distant metastases. Biopsy confirms squamous cell carcinoma. CT chest shows no involvement of anterior commissure or subglottis. What is the drug of choice for induction chemotherapy in this patient with locally advanced laryngeal carcinoma?

## Induction Chemotherapy for Laryngeal Carcinoma **Key Point:** Cisplatin and 5-fluorouracil (5-FU) is the gold-standard induction chemotherapy regimen for locally advanced squamous cell carcinoma of the larynx, particularly when laryngeal preservation is the goal. ### Rationale for Cisplatin + 5-FU **High-Yield:** The VAC regimen (Vinblastine, Actinomycin D, Cyclophosphamide) and later PF regimen (Cisplatin + 5-FU) were established by the landmark RTOG trials (particularly RTOG 91-11) as the standard induction chemotherapy before concurrent chemoradiation for laryngeal preservation. **Clinical Pearl:** In locally advanced laryngeal cancer (Stage III–IV), induction chemotherapy followed by concurrent chemoradiation offers superior laryngeal preservation rates compared to radiation alone, with 2-year laryngeal preservation rates of ~60–70%. ### Mechanism of Action | Agent | Mechanism | Role in Laryngeal CA | |-------|-----------|---------------------| | Cisplatin | Platinum alkylating agent; DNA cross-linking | Synergistic with 5-FU; radiosensitizer | | 5-Fluorouracil | Antimetabolite; thymidylate synthase inhibitor | Enhances cisplatin effect; improves locoregional control | **Warning:** Cisplatin is nephrotoxic and ototoxic — baseline renal function and audiometry are mandatory. Adequate hydration and mesna are required. ### Treatment Algorithm for Locally Advanced Laryngeal Carcinoma ```mermaid flowchart TD A[Locally Advanced Laryngeal SCC]:::outcome --> B{Laryngeal Preservation Goal?}:::decision B -->|Yes| C[Induction Chemotherapy: Cisplatin + 5-FU]:::action C --> D[Concurrent Chemoradiation]:::action D --> E{Response?}:::decision E -->|Complete/Partial| F[Larynx Preserved]:::outcome E -->|No Response| G[Total Laryngectomy]:::action B -->|No| H[Primary Total Laryngectomy ± Adjuvant RT]:::action ``` **Mnemonic:** **PF-CRT** = **P**latin + **F**luorouracil followed by **C**oncurrent **R**adio**T**herapy (the standard for laryngeal preservation). ### Dosing Schedule - **Cisplatin:** 100 mg/m² IV on day 1 - **5-FU:** 1000 mg/m²/day IV continuous infusion, days 1–5 - Repeat every 3 weeks for 3 cycles **Tip:** Always assess performance status (ECOG 0–1 preferred) and renal function (eGFR >60) before cisplatin-based therapy. [cite:Harrison 21e Ch 97]