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Cancer. 2017 Dec 1;123(23):4653-4662. doi: 10.1002/cncr.30920. Epub 2017 Aug 7.

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).

Author information

1
Department of Medical Oncology, Yale University School of Medicine and Yale Cancer Center, New Haven, Connecticut.
2
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Eastern Cooperative Oncology Group-ACRIN Biostatistics Center, Boston, Massachusetts.
3
Division of Oncology, Department of Medicine, Stanford University and Veterans Affairs Palo Alto Health Care System, Stanford, California.
4
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
5
Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York.
6
Sanford North Fargo Clinic, Fargo, North Dakota.
7
Santa Clara Valley Medical Center, San Jose, California.
8
North Shore University Health System, Evanston, Illinois.
9
Porter Cancer Center, Denver, Colorado.
10
San Juan City Hospital, San Juan, Puerto Rico.
11
Sandra and Malcolm Berman Cancer Institute, Baltimore, Maryland.
12
University of Michigan, Ann Arbor, Michigan.
13
University of Minnesota, Minneapolis, Minnesota.
14
Department of Medicine Hematology/Oncology, University of Rochester Medical Center, Rochester, New York.

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.

KEYWORDS:

chemoprevention; head and neck cancer; oral cancer; randomized controlled trial; second primary cancer

PMID:
28786105
PMCID:
PMC5693641
DOI:
10.1002/cncr.30920
[Indexed for MEDLINE]
Free PMC Article

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