Abstract
BACKGROUND: 13-Cis retinoic acid (13-CRA) is a synthetic vitamin A derivative. High-dose 13-CRA in patients with squamous cell cancers of the head and neck (SCCHNs) reduces the incidence of second primary tumors (SPTs). The authors report long-term results from a phase 3 randomized trial that compared treatment with low-dose 13-CRA versus placebo for patients who had early stage SCCHN, with a focus on the development of SPTs and overall survival (OS). METHODS: In total, 176 patients who received treatment for stage I/II SCCHN were randomized to receive either low-dose 13-CRA (weight-based dose of 7.5 mg or 10 mg) or placebo for 2 years. A competing-risk approach and the log-rank test were used to compare the time to SPT and OS, respectively, between groups. RESULTS: 13-CRA neither significantly reduced the cumulative incidence of SPT (P =.61) nor improved the time to SPT (hazard ratio [HR] for 13-CRA/placebo; 0.86; P =.61). Despite limited power, there was a trend toward improved OS for the 13-CRA arm (HR, 0.75; P =.14), particularly among patients whose index tumor was surgically excised (N = 26; HR, 0.50; P =.057) and among women (N = 39; HR, 0.44; P =.065) and never/former smokers (N = 129; HR, 0.61; P =.055), with a median follow-up of 16 years. The main 13-CRA related toxicities were dry skin and cheilitis. CONCLUSIONS: Treatment with low-dose 13-CRA for 2 years did not decrease the incidence of SPT; subset analysis indicates a potential survival advantage among patients who are women and never/former smokers. More targeted interventions based on clinical risk factors and molecular characterization of tumors may yield greater success in future prevention trials. Cancer 2017;123:4653-4662.
Original language | English (US) |
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Pages (from-to) | 4653-4662 |
Number of pages | 10 |
Journal | Cancer |
Volume | 123 |
Issue number | 23 |
DOIs | |
State | Published - Dec 1 2017 |
Keywords
- chemoprevention
- head and neck cancer
- oral cancer
- randomized controlled trial
- second primary cancer
ASJC Scopus subject areas
- Oncology
- Cancer Research