Double‐blind, randomized phase 3 trial of low‐dose 13‐cis retinoic acid in the prevention of second primaries in head and neck cancer: Long‐term follow‐up of a trial of the Eastern Cooperative Oncology Group‐ACRIN Cancer Research Group (C0590)
Year: 2017
Type: article
Study design: Clinical Trial
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. © 2017 American Cancer Society.
Source: Cancer
DOI: 10.1002/cncr.30920
Institutions: Yale Cancer Center, Yale University, Eastern Cooperative Oncology Group, Dana-Farber Cancer Institute, VA Palo Alto Health Care System, Stanford University, Mayo Clinic, University of Rochester Medicine, Santa Clara Valley Medical Center, Endeavor Health, San Juan City Hospital, University of Michigan, University of Minnesota, University of Rochester
Language: English
Topic: Head and Neck Cancer Studies
Subfield: Otorhinolaryngology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1257575315, G1266854846, Alliance Statistics and Data Management Center, G1539327064, Stanford University NCTN- Network Lead Academic Site, Sanford Community Cancer Consortium, G2017411191, ECOG - ACRIN CCOP RESEARCH BASE GRANT - CORE, G286468852, Johns Hopkins University NCTN Lead Academic Site Program, Western States Cancer Research NCORP, Sanford Community Cancer Program of the North Central Plains (NCORP), G358241105, G359183106, G3650305600, Eastern Cooperative Oncology Group, ECOG Clinical Trials, G4205753748, G42877212, NRG Oncology Network Group Operations Center, G4413867291, Southwest Oncology Group, ECOG-ACRIN NCORP Research Base, G4768247927, Naional Cancer Institute, Naitonal Clinical Trials Network U10 Lead Academic Site, G4879059600, Community Clinical Oncology Program, CCOP: Colorado Cancer Research Program, Community Clinical Oncology Program, G5671623325, G5672437777, G5765316850, G5805678965, North Central Cancer Treatment Group, G613628225, UM LAPs- U10 Grant, NCI, National Clinical Trials Network Lead Academic Participating Site (LAPS) UG1, Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, San Juan Minority-Based Community Clinical Oncology Program, Yale Cancer Center NCTN, Puerto Rico Minority Underserved NCI Community Oncology Research Program (Puerto Rico MUNCORP), Sanford Community Cancer Consortium, G8526228613, Alliance for Clinical Trials in Oncology Operations Center, G9000028669, G9000211914, G9000289902, G9000291439, Yale Clinical and Translational Science Award, NRG Oncology - Statistical and Data Management Center
OpenAlex ID: W2743269670