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Cancer Prev Res (Phila). 2016 Dec;9(12):906-914. Epub 2016 Sep 22.

A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial Dysplasia.

Author information

1
British Columbia Cancer Agency, Vancouver, British Columbia, Canada. slam2@bccancer.bc.ca.
2
Mayo Clinic, Rochester, Minnesota.
3
Boston University Medical Center, Boston, Massachusetts.
4
New Mexico Veteran's Health Care System, Albuquerque, New Mexico.
5
Fiona Stanley Hospital, Palmyra DC, Western Australia.
6
St. Paul's Hospital, Vancouver, British Columbia, Canada.
7
British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
8
University of Utah, Salt Lake City, Utah.
9
Vancouver General Hospital, Vancouver, British Columbia.
10
Mayo Clinic, Scottsdale, Arizona.
11
Division of Cancer Prevention, National Cancer Institute, NIH, Bethesda, Maryland.

Abstract

Previous preclinical studies and a phase I clinical trial suggested that myo-inositol may be a safe and effective lung cancer chemopreventive agent. We conducted a randomized, double blind, placebo-controlled phase IIb study to determine the chemopreventive effects of myo-inositol in smokers with bronchial dysplasia. Smokers with ≥1 site of dysplasia identified by autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive oral placebo or myo-inositol, 9 g once a day for 2 weeks, and then twice a day for 6 months. The primary endpoint was change in dysplasia rate after 6 months of intervention on a per-participant basis. Other trial endpoints reported herein include Ki-67 labeling index, blood and bronchoalveolar lavage fluid (BAL) levels of proinflammatory, oxidant/antioxidant biomarkers, and an airway epithelial gene expression signature for PI3K activity. Seventy-four (n = 38 myo-inositol and n = 36 placebo) participants with a baseline and 6-month bronchoscopy were included in all efficacy analyses. The complete response and the progressive disease rates were 26.3% versus 13.9% and 47.4% versus 33.3%, respectively, in the myo-inositol and placebo arms (P = 0.76). Compared with placebo, myo-inositol intervention significantly reduced IL6 levels in BAL over 6 months (P = 0.03). Among those with a complete response in the myo-inositol arm, there was a significant decrease in a gene expression signature reflective of PI3K activation within the cytologically normal bronchial airway epithelium (P = 0.002). The heterogeneous response to myo-inositol suggests a targeted therapy approach based on molecular alterations is needed in future clinical trials to determine the efficacy of myo-inositol as a chemopreventive agent. Cancer Prev Res; 9(12); 906-14.

PMID:
27658890
PMCID:
PMC5136333
DOI:
10.1158/1940-6207.CAPR-15-0254
[Indexed for MEDLINE]
Free PMC Article

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