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


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.

  • Allen Ziegler KL
  • Aubry MC
  • Beane J
  • Bild A
  • Gesthalter Y
  • Harmsen WS
  • Ionescu DN
  • Johnson E
  • Lam S
  • Lenburg ME
  • Limburg PJ
  • Liu G
  • Mandrekar SJ
  • Mao JT
  • Mayo J
  • McWilliams A
  • Midthun DE
  • Seisler DK
  • Shaipanich T
  • Sin DD
  • Smith J
  • Spira AE
  • Szabo E
  • Tazelaar H
  • Yi JE
PubMed ID
Appears In
Cancer Prev Res (Phila), 2016, 9 (12)