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© The Author 2006. Published by Oxford University Press.
ARTICLE |
Randomized Phase III Trial of Low-dose Isotretinoin for Prevention of Second Primary Tumors in Stage I and II Head and Neck Cancer Patients
Affiliations of authors: Winship Cancer Institute/Emory University, Atlanta, GA (FRK, DMS); University of Texas M. D. Anderson Cancer Center, Houston, TX (JJL, SML, ESK, BW, LF, HG, WKH); Maimonides Medical Center, New York, NY (JSC); University of California, San Francisco, CA (KF); Hamilton Regional Cancer Center, Hamilton, Ontario, Canada (IH); Southwest Oncology Group, San Antonio, TX (SML); Radiation Therapy Oncology Group, Philadelphia, PA (FRK, JSC, RW, TFP, GS, IH, KF, DMS); Protein Design Labs, Freemont, CA (SEB); University of Chicago, Chicago, IL (EEV); National Quality Forum, Washington, DC (RW); McGill Unversity, Montreal, Quebec, Canada (GS); Cancer and Leukemia Group B, Chicago, IL (EEV); Community Clinical Oncology Programs, Washington, DC (RW, SEB); Texas Community Oncology Network, Houston, TX (RW)
Correspondence to: Fadlo R. Khuri, MD, Winship Cancer Institute/Emory University School of Medicine, 1365 Clifton Rd., NE, Bldg. C-3094, Atlanta, GA 30322 (e-mail: fkhuri{at}emory.edu).
Background: Isotretinoin (13-cis-retinoic acid) is a synthetic vitamin A derivative, or retinoid, widely used in the treatment of cystic acne. Preclinical and clinical studies of high-dose isotretinoin in patients with head and neck squamous cell cancer (HNSCC) have produced encouraging results. We conducted a phase III randomized trial of low-dose isotretinoin versus placebo in early-stage HNSCC patients to assess its effect on second primary tumor incidence and survival. Methods: We randomly assigned 1190 patients who had been treated for stage I or II HNSCC to receive either low-dose isotretinoin (30 mg/day) or placebo for 3 years. The patients were monitored for up to 4 more years. Survival was analyzed by the Kaplan–Meier method, and Cox proportional hazards models were used for multivariable survival analysis. All statistical tests were two-sided. Results: Isotretinoin did not statistically significantly reduce the rate of second primary tumors (hazard ratio [HR] = 1.06, 95% confidence interval [CI] = 0.83 to 1.35) or increase survival (HR = 1.03, 95% CI = 0.81 to 1.32) compared with placebo in patients with early-stage HNSCC. Current smokers had a higher rate of second primary tumors than that of never (HR = 1.64, 95% CI = 1.08 to 2.50) or former (HR = 1.32, 95% CI = 1.01 to 1.71) smokers. The hazard ratio of death from any cause for current smokers versus never smokers was 2.51 (95% CI = 1.54 to 4.10) and for current smokers versus former smokers was 1.60 (95% CI = 1.23 to 2.07). Major sites of second primary tumors (n = 261) included lung (31%), oral cavity (17%), larynx (8%), and pharynx (5%). Conclusions: Low-dose isotretinoin was not effective in reducing the rate of second primary tumors or death or smoking-related disease. Smoking statistically significantly increased the rate of second primary tumors and death. Ongoing trials are testing higher doses of isotretinoin as part of combination bioadjuvant therapeutic methods for patients with locally advanced HNSCC.
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J Natl Cancer Inst 2006 98: 426-427.[Extract] [Full Text] [PDF]
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