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

Cancer Prev Res (Phila). 2016 Dec;9(12):906-914. doi: 10.1158/1940-6207.CAPR-15-0254. Epub 2016 Sep 22.

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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism
  • Biopsy
  • Bronchi / drug effects*
  • Bronchi / pathology*
  • Bronchoalveolar Lavage Fluid
  • Bronchoscopy
  • Chemoprevention
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Glucose / metabolism
  • Humans
  • Hyperplasia / drug therapy
  • Hyperplasia / pathology
  • Inositol / administration & dosage
  • Inositol / pharmacology
  • Inositol / therapeutic use*
  • Ki-67 Antigen / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control*
  • Male
  • Metaplasia / drug therapy
  • Metaplasia / pathology
  • Middle Aged
  • Optical Imaging
  • Phosphatidylinositol 3-Kinases / genetics
  • Smoking / adverse effects*
  • Tomography, Spiral Computed
  • Vitamin B Complex / administration & dosage
  • Vitamin B Complex / pharmacology
  • Vitamin B Complex / therapeutic use*

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Vitamin B Complex
  • Inositol
  • Phosphatidylinositol 3-Kinases
  • Glucose