Publications

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

Author(s): Lam S,  Mandrekar SJ,  Gesthalter Y,  Allen Ziegler KL,  Seisler DK,  Midthun DE,  Mao JT,  Aubry MC,  McWilliams A,  Sin DD,  Shaipanich T,  Liu G,  Johnson E,  Bild A,  Lenburg ME,  Ionescu DN,  Mayo J,  Yi JE,  Tazelaar H,  Harmsen WS,  Smith J,  Spira AE,  Beane J,  Limburg PJ,  Szabo E,  Cancer Prevention Network

Journal: Cancer Prev Res (Phila)

Date: 2016 Dec

Major Program(s) or Research Group(s): LUACRG

PubMed ID: 27658890

PMC ID: PMC5136333

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. ©2016 AACR.