This Article Full Text Full Text (PDF) Perspective on this Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McLaren, C. E. Articles by Meyskens, F. L. Search for Related Content PubMed PubMed Citation Articles by McLaren, C. E. Articles by Meyskens, F. L., Jr. Related Collections Clinical Intervention Clinical Intervention: Definitive (Phase III) Clinical or Translational Trials Commentary

Longitudinal Assessment of Air Conduction Audiograms in a Phase III Clinical Trial of Difluoromethylornithine and Sulindac for Prevention of Sporadic Colorectal Adenomas

Authors' Affiliations: ¹ Department of Epidemiology, ² Chao Family Comprehensive Cancer Center, and ³ Department of Statistics, University of California, Irvine, Irvine, California; and ⁴ Arizona Cancer Center, University of Arizona, Tucson, Arizona

Requests for reprints: Christine E. McLaren, Department of Epidemiology, College of Health Sciences, University of California, Irvine, 224 Irvine Hall, Irvine, CA 92697-7550. Phone: 949-824-4007; Fax: 949-824-4773; E-mail: cmclaren{at}uci.edu.

A phase III clinical trial assessed the recurrence of adenomatous polyps after treatment for 36 months with difluoromethylornithine (DFMO) plus sulindac or matched placebos. Temporary hearing loss is a known toxicity of treatment with DFMO, thus a comprehensive approach was developed to analyze serial air conduction audiograms. The generalized estimating equation method estimated the mean difference between treatment arms with regard to change in air conduction pure tone thresholds while accounting for within-subject correlation due to repeated measurements at frequencies. Based on 290 subjects, there was an average difference of 0.50 dB between subjects treated with DFMO plus sulindac compared with those treated with placebo (95% confidence interval, –0.64 to 1.63 dB; P = 0.39), adjusted for baseline values, age, and frequencies. In the normal speech range of 500 to 3,000 Hz, an estimated difference of 0.99 dB (–0.17 to 2.14 dB; P = 0.09) was detected. Dose intensity did not add information to models. There were 14 of 151 (9.3%) in the DFMO plus sulindac group and 4 of 139 (2.9%) in the placebo group who experienced at least 15 dB hearing reduction from baseline in 2 or more consecutive frequencies across the entire range tested (P = 0.02). Follow-up air conduction done at least 6 months after end of treatment showed an adjusted mean difference in hearing thresholds of 1.08 dB (–0.81 to 2.96 dB; P = 0.26) between treatment arms. There was no significant difference in the proportion of subjects in the DFMO plus sulindac group who experienced clinically significant hearing loss compared with the placebo group. The estimated attributable risk of ototoxicity from exposure to the drug is 8.4% (95% confidence interval, –2.0% to 18.8%; P = 0.12). There is a <2 dB difference in mean threshold for patients treated with DFMO plus sulindac compared with those treated with placebo.

Key Words: Difluoromethylornithine • air conduction audiograms • ototoxicity • generalized estimating equations • chemoprevention

Commentary

Assessing Toxicity in Cancer Chemoprevention Trials: The Other Side of the Coin

Gary E. Goodman
Cancer Prevention Research 2008 1: 499-502. [Full Text] [PDF]

This article has been cited by other articles:

				E. W. Gerner Cancer Chemoprevention Locks onto a New Polyamine Metabolic Target Cancer Prevention Research, February 1, 2010; 3(2): 125 - 127. [Abstract] [Full Text] [PDF]

				C. A. Elmets and M. Athar Targeting Ornithine Decarboxylase for the Prevention of Nonmelanoma Skin Cancer in Humans Cancer Prevention Research, January 1, 2010; 3(1): 8 - 11. [Abstract] [Full Text] [PDF]

				G. E. Goodman Assessing Toxicity in Cancer Chemoprevention Trials: The Other Side of the Coin Cancer Prevention Research, December 1, 2008; 1(7): 499 - 502. [Full Text] [PDF]