TY - JOUR
T1 - A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial Dysplasia
AU - Lam, Stephen
AU - Mandrekar, Sumithra J.
AU - Gesthalter, Yaron
AU - Allen Ziegler, Katie L.
AU - Seisler, Drew K.
AU - Midthun, David E.
AU - Mao, Jenny T.
AU - Aubry, Marie Christine
AU - McWilliams, Annette
AU - Sin, Don D.
AU - Shaipanich, Tawimas
AU - Liu, Gang
AU - Johnson, Evan
AU - Bild, Andrea
AU - Lenburg, Marc E.
AU - Ionescu, Diana N.
AU - Mayo, John
AU - Yi, Joanne
AU - Tazelaar, Henry
AU - Harmsen, William S.
AU - Smith, Judith
AU - Spira, Avrum E.
AU - Beane, Jennifer
AU - Limburg, Paul J.
AU - Szabo, Eva
N1 - Publisher Copyright: © 2016 American Association for Cancer Research.
PY - 2016/12
Y1 - 2016/12
N2 - 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 myoinositol 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.
AB - 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 myoinositol 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.
UR - https://www.scopus.com/pages/publications/85008423171
UR - https://www.scopus.com/pages/publications/85008423171#tab=citedBy
U2 - 10.1158/1940-6207.CAPR-15-0254
DO - 10.1158/1940-6207.CAPR-15-0254
M3 - Article
C2 - 27658890
SN - 1940-6207
VL - 9
SP - 906
EP - 914
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 12
ER -