Background
Phase III, prospective randomized trial (Department of Veterans Affairs). 332 patients with previously untreated, advanced (Stage III or IV) laryngeal squamous carcinoma. First prospective RCT demonstrating that larynx preservation with induction chemotherapy + RT could achieve equivalent survival to standard laryngectomy, establishing the principle of organ-preservation therapy in laryngeal cancer.
Interventions and follow up
Arm A: Induction chemotherapy (cisplatin 100 mg/m² IV day 1 + fluorouracil 1000 mg/m²/day continuous infusion days 1–5, q3wks × 2–3 cycles) followed by definitive RT (66–76 Gy) — responders only; non-responders proceeded to laryngectomy + RT
Arm B: Total laryngectomy + partial pharyngectomy + radical neck dissection + post-operative RT (50–74 Gy)
Primary endpoint: Survival (equivalence)
mFollow up: Median 33 month
Arm B: Total laryngectomy + partial pharyngectomy + radical neck dissection + post-operative RT (50–74 Gy)
Primary endpoint: Survival (equivalence)
mFollow up: Median 33 month
Results
2-year estimated survival: 68% vs 68%, P=.98 — equivalent
Larynx preservation: 64% of all patients in chemotherapy arm; 64% of those alive and disease-free
Local recurrence: More frequent in chemotherapy arm (P=.0005)
Distant metastases: Fewer in chemotherapy arm (P=.016)
Larynx preservation: 64% of all patients in chemotherapy arm; 64% of those alive and disease-free
Local recurrence: More frequent in chemotherapy arm (P=.0005)
Distant metastases: Fewer in chemotherapy arm (P=.016)
Adverse events
Main adverse events: Chemotherapy toxicities (myelosuppression, mucositis, nausea). Post-laryngectomy surgical morbidity in surgery arm. 36% of chemotherapy arm patients required salvage laryngectomy.
Conclusions
Induction chemotherapy followed by definitive radiotherapy achieves equivalent survival to standard total laryngectomy in advanced laryngeal cancer, while preserving the larynx in 64% of patients. This trial established the proof-of-concept for larynx preservation in laryngeal cancer.
Key Limitations
Key Limitations: Equivalence study — not designed to show superiority of either arm. The chemotherapy arm had higher local recurrence rates despite equivalent survival, potentially offset by fewer distant metastases. Follow-up was relatively short (median 33 months) for a curative trial — long-term quality-of-life data on preserved larynx function not reported. The chemotherapy regimen (cisplatin/5-FU induction) was superseded by concurrent CRT (RTOG 9111) as a more effective larynx preservation strategy. Applicable primarily to T2–T4 glottic/supraglottic tumors — T4 with cartilage invasion is a relative contraindication to larynx preservation.
Clinical Context
The VA Larynx Trial established larynx preservation as a viable and equivalent strategy for advanced laryngeal cancer. It was followed by RTOG 9111, which showed that concurrent cisplatin-RT (not induction chemo) achieves the highest larynx preservation rates. Current standard for resectable advanced laryngeal cancer: concurrent cisplatin-RT (RTOG 9111 regimen) if larynx preservation is sought; total laryngectomy if T4 with cartilage invasion or large bulky disease. Swallowing function and voice quality after preservation must be assessed prospectively.