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

Stephen Lam, Sumithra J. Mandrekar, Yaron Gesthalter, Katie L. Allen Ziegler, Drew K. Seisler, David E. Midthun, Jenny T. Mao, Marie Christine Aubry, Annette McWilliams, Don D. Sin, Tawimas Shaipanich, Gang Liu, Evan Johnson, Andrea Bild, Marc E. Lenburg, Diana N. Ionescu, John Mayo, Joanne Yi, Henry Tazelaar, William S. HarmsenJudith Smith, Avrum E. Spira, Jennifer Beane, Paul J. Limburg, Eva Szabo

Research output: Contribution to journalArticle

16 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)906-914
Number of pages9
JournalCancer Prevention Research
Volume9
Issue number12
DOIs
StatePublished - Dec 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Lam, S., Mandrekar, S. J., Gesthalter, Y., Allen Ziegler, K. L., Seisler, D. K., Midthun, D. E., Mao, J. T., Aubry, M. C., McWilliams, A., Sin, D. D., Shaipanich, T., Liu, G., Johnson, E., Bild, A., Lenburg, M. E., Ionescu, D. N., Mayo, J., Yi, J., Tazelaar, H., ... Szabo, E. (2016). A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial Dysplasia. Cancer Prevention Research, 9(12), 906-914. https://doi.org/10.1158/1940-6207.CAPR-15-0254