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Cancer prevention research (Philadelphia, Pa.)
Dec, 2016;9 (12): 906-914.

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 Eunhee Yi, Henry Tazelaar, William S Harmsen, Judith Smith, Avrum E Spira, Jennifer Beane, Paul J Limburg, Eva Szabo, Cancer Prevention Network
Author Information
  1. Stephen Lam: British Columbia Cancer Agency, Vancouver, British Columbia, Canada. slam2@bccancer.bc.ca.
  2. Sumithra J Mandrekar: Mayo Clinic, Rochester, Minnesota.
  3. Yaron Gesthalter: Boston University Medical Center, Boston, Massachusetts.
  4. Katie L Allen Ziegler: Mayo Clinic, Rochester, Minnesota.
  5. Drew K Seisler: Mayo Clinic, Rochester, Minnesota.
  6. David E Midthun: Mayo Clinic, Rochester, Minnesota.
  7. Jenny T Mao: New Mexico Veteran's Health Care System, Albuquerque, New Mexico.
  8. Marie Christine Aubry: Mayo Clinic, Rochester, Minnesota.
  9. Annette McWilliams: Fiona Stanley Hospital, Palmyra DC, Western Australia.
  10. Don D Sin: St. Paul's Hospital, Vancouver, British Columbia, Canada.
  11. Tawimas Shaipanich: British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
  12. Gang Liu: Boston University Medical Center, Boston, Massachusetts.
  13. Evan Johnson: Boston University Medical Center, Boston, Massachusetts.
  14. Andrea Bild: University of Utah, Salt Lake City, Utah.
  15. Marc E Lenburg: Boston University Medical Center, Boston, Massachusetts.
  16. Diana N Ionescu: British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
  17. John Mayo: Vancouver General Hospital, Vancouver, British Columbia.
  18. Joanne Eunhee Yi: Mayo Clinic, Rochester, Minnesota.
  19. Henry Tazelaar: Mayo Clinic, Scottsdale, Arizona.
  20. William S Harmsen: Mayo Clinic, Rochester, Minnesota.
  21. Judith Smith: Division of Cancer Prevention, National Cancer Institute, NIH, Bethesda, Maryland.
  22. Avrum E Spira: Boston University Medical Center, Boston, Massachusetts.
  23. Jennifer Beane: Boston University Medical Center, Boston, Massachusetts.
  24. Paul J Limburg: Mayo Clinic, Rochester, Minnesota.
  25. Eva Szabo: Division of Cancer Prevention, National Cancer Institute, NIH, Bethesda, Maryland.
PMID: 27658890 DOI: 10.1158/1940-6207.CAPR-15-0254

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.

References

  1. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 [PMID: 16199517]
  2. Cancer. 1996 Sep 1;78(5):1004-10 [PMID: 8780538]
  3. Cancer Prev Res (Phila). 2014 Dec;7(12 ):1179-85 [PMID: 24755313]
  4. J Natl Cancer Inst. 2002 Jul 3;94(13):1001-9 [PMID: 12096085]
  5. Cancer Prev Res (Phila). 2009 Apr;2(4):370-6 [PMID: 19336734]
  6. Clin Cancer Res. 2004 Oct 1;10(19):6502-11 [PMID: 15475437]
  7. Bioinformatics. 2010 Jan 1;26(1):139-40 [PMID: 19910308]
  8. BMC Bioinformatics. 2011 Aug 04;12:323 [PMID: 21816040]
  9. N Engl J Med. 2003 Mar 6;348(10):891-9 [PMID: 12621133]
  10. Chest. 1985 Dec;88(6):856-9 [PMID: 4064774]
  11. Int J Oncol. 2003 Dec;23(6):1607-13 [PMID: 14612933]
  12. Lung Cancer. 2014 Apr;84(1):13-22 [PMID: 24524818]
  13. Genome Biol. 2014 Feb 03;15(2):R29 [PMID: 24485249]
  14. Am J Respir Crit Care Med. 2016 Oct 15;194(8):948-960 [PMID: 27104832]
  15. J Thorac Oncol. 2006 Jan;1(1):61-8 [PMID: 17409828]
  16. Cancer Metastasis Rev. 2010 Mar;29(1):5-14 [PMID: 20112052]
  17. Sci Transl Med. 2010 Apr 7;2(26):26ra25 [PMID: 20375364]
  18. BMJ. 2000 Aug 5;321(7257):323-9 [PMID: 10926586]
  19. N Engl J Med. 2003 Mar 6;348(10):883-90 [PMID: 12621132]
  20. Chest. 2013 May;143(5 Suppl):e40S-60S [PMID: 23649449]
  21. Am J Respir Crit Care Med. 2015 Dec 15;192(12 ):1411-3 [PMID: 26669471]
  22. Nucleic Acids Res. 2015 Apr 20;43(7):e47 [PMID: 25605792]
  23. Thorax. 2007 Jan;62(1):43-50 [PMID: 16825337]
  24. Cancer Epidemiol Biomarkers Prev. 2006 Aug;15(8):1526-31 [PMID: 16896044]
  25. Carcinogenesis. 1993 Sep;14(9):1975-7 [PMID: 8403228]
  26. Fed Proc. 1979 Oct;38(11):2528-34 [PMID: 488376]
  27. Chest. 1998 Mar;113(3):696-702 [PMID: 9515845]
  28. Cancer Res. 1996 Nov 15;56(22):5132-5 [PMID: 8912846]
  29. Bioinformatics. 2012 Aug 15;28(16):2184-5 [PMID: 22743226]
  30. Cancer Prev Res (Phila). 2011 Jun;4(6):793-802 [PMID: 21636546]
  31. Am J Respir Crit Care Med. 2003 Nov 15;168(10):1167-73 [PMID: 12882756]
  32. J Histochem Cytochem. 1991 Jun;39(6):741-8 [PMID: 1709656]
  33. CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29 [PMID: 24399786]

Grants

  1. N01CN35000/NCI NIH HHS

MeSH Term

Aged
Biomarkers, Tumor
Biopsy
Bronchi
Bronchoalveolar Lavage Fluid
Bronchoscopy
Chemoprevention
Dose-Response Relationship, Drug
Double-Blind Method
Female
Glucose
Humans
Hyperplasia
Inositol
Ki-67 Antigen
Lung Neoplasms
Male
Metaplasia
Middle Aged
Optical Imaging
Phosphatidylinositol 3-Kinases
Smoking
Tomography, Spiral Computed
Vitamin B Complex

Chemicals

Biomarkers, Tumor
Ki-67 Antigen
Vitamin B Complex
Inositol
Phosphatidylinositol 3-Kinases
Glucose
Clinical Trial, Phase II Journal Article Randomized Controlled Trial

Links to CNCB-NGDC Resources

GEN: GEND000175 (Airway epithelial cells from smokers treated with myo-inositol or placebo)

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