BACKGROUND: To develop guidelines for the conduct of phase III clinical trials of larynx preservation in patients with locally advanced laryngeal and hypopharyngeal cancer.
METHODS: A multidisciplinary international consensus panel developed recommendations after reviewing results from completed phase III randomized trials, meta-analyses, and published clinical reports with updates available through November 2007. The guidelines were reviewed and approved by the panel.
RESULTS: The trial population should include patients with T2 or T3 laryngeal or hypopharyngeal squamous cell carcinoma not considered for partial laryngectomy and exclude those with laryngeal dysfunction or age more than 70 years. Functional assessments should include speech and swallowing. Voice should be routinely assessed with a simple, validated instrument. The primary endpoint should capture survival and function. The panel created a new endpoint: laryngo-esophageal dysfunction-free survival. Events are death, local relapse, total or partial laryngectomy, tracheotomy at 2 years or later, or feeding tube at 2 years or later. Recommended secondary endpoints are overall survival, progression-free survival, locoregional control, time to tracheotomy, time to laryngectomy, time to discontinuation of feeding tube, and quality of life/patient reported outcomes. Correlative biomarker studies for near-term trials should include EGFR, ERCC-1, E-cadherin and beta-catenin, epiregulin and amphiregulin, and TP53 mutation.
CONCLUSIONS: Revised trial designs in several key areas are needed to advance the study of larynx preservation. With consistent methodologies, clinical trials can more effectively evaluate and quantify the therapeutic benefit of novel treatment options for patients with locally-advanced laryngeal and hypopharyngeal cancer.