Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial

Ramesh K. Wali, Laura Bianchi, Sonia Kupfer, Mart De La Cruz, Borko Jovanovic, Christopher Weber, Michael J. Goldberg, L. M. Rodriguez, Raymond Bergan, David Rubin, Mary Beth Tull, Ellen Richmond, Beth Parker, Seema Khan, Hemant K. Roy

Research output: Contribution to journalArticle

Abstract

Chemoprevention represents an attractive modality against colorectal cancer (CRC) although widespread clinical implementation of promising agents (e.g. aspirin/NSAIDS) have been stymied by both suboptimal efficacy and concerns over toxicity. This highlights the need for better agents. Several groups, including our own, have reported that the over-the-counter laxative polyethylene glycol (PEG) has remarkable efficacy in rodent models of colon carcinogenesis. In this study, we undertook the first randomized human trial to address the role of PEG in prevention of human colonic neoplasia. This was a double-blind, placebo-controlled, three-arm trial where eligible subjects were randomized to 8g PEG-3350 (n = 27) or 17g PEG-3350 (n = 24), or placebo (n = 24; maltodextrin) orally for a duration of six months. Our initial primary endpoint was rectal aberrant crypt foci (ACF) but this was changed during protocol period to rectal mucosal epidermal growth factor receptor (EGFR). Of the 87 patients randomized, 48 completed study primary endpoints and rectal EGFR unchanged PEG treatment. Rectal ACF had a trend suggesting potentially reduction with PEG treatment (pre-post change 1.7 in placebo versus -0.3 in PEG 8+ 17g doses, p = 0.108). Other endpoints (proliferation, apoptosis, expression of SNAIL and E-cadherin), previously noted to be modulated in rodent models, appeared unchanged with PEG treatment in this clinical trial. We conclude that PEG was generally well tolerated with the trial failing to meet primary efficacy endpoints. However, rectal ACFs demonstrated a trend (albeit statistically insignificant) for suppression with PEG. Moreover, all molecular assays including EGFR were unaltered with PEG underscoring issues with lack of translatability of biomarkers from preclinical to clinical trials. This data May provide the impetus for future clinical trials on PEG using more robust biomarkers of chemoprevention.

Original languageEnglish (US)
Article numbere0193544
JournalPLoS One
Volume13
Issue number4
DOIs
StatePublished - Apr 1 2018

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polyethylene glycol
placebos
Placebos
neoplasms
Neoplasms
endpoints
Epidermal Growth Factor Receptor
Aberrant Crypt Foci
Chemoprevention
Clinical Trials
Biomarkers
clinical trials
chemoprevention
Rodentia
biomarkers
rodents
Laxatives
laxatives
Cadherins
maltodextrins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Wali, R. K., Bianchi, L., Kupfer, S., De La Cruz, M., Jovanovic, B., Weber, C., ... Roy, H. K. (2018). Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial. PLoS One, 13(4), [e0193544]. https://doi.org/10.1371/journal.pone.0193544

Prevention of colonic neoplasia with polyethylene glycol : A short term randomized placebo-controlled double-blinded trial. / Wali, Ramesh K.; Bianchi, Laura; Kupfer, Sonia; De La Cruz, Mart; Jovanovic, Borko; Weber, Christopher; Goldberg, Michael J.; Rodriguez, L. M.; Bergan, Raymond; Rubin, David; Tull, Mary Beth; Richmond, Ellen; Parker, Beth; Khan, Seema; Roy, Hemant K.

In: PLoS One, Vol. 13, No. 4, e0193544, 01.04.2018.

Research output: Contribution to journalArticle

Wali, RK, Bianchi, L, Kupfer, S, De La Cruz, M, Jovanovic, B, Weber, C, Goldberg, MJ, Rodriguez, LM, Bergan, R, Rubin, D, Tull, MB, Richmond, E, Parker, B, Khan, S & Roy, HK 2018, 'Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial', PLoS One, vol. 13, no. 4, e0193544. https://doi.org/10.1371/journal.pone.0193544
Wali, Ramesh K. ; Bianchi, Laura ; Kupfer, Sonia ; De La Cruz, Mart ; Jovanovic, Borko ; Weber, Christopher ; Goldberg, Michael J. ; Rodriguez, L. M. ; Bergan, Raymond ; Rubin, David ; Tull, Mary Beth ; Richmond, Ellen ; Parker, Beth ; Khan, Seema ; Roy, Hemant K. / Prevention of colonic neoplasia with polyethylene glycol : A short term randomized placebo-controlled double-blinded trial. In: PLoS One. 2018 ; Vol. 13, No. 4.
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