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

التفاصيل البيبلوغرافية
العنوان: Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial.
المؤلفون: 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
المصدر: PLoS ONE, Vol 13, Iss 4, p e0193544 (2018)
بيانات النشر: Public Library of Science (PLoS), 2018.
سنة النشر: 2018
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: 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. TRIAL REGISTRATION:ClinicalTrials.gov NCT00828984.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: http://europepmc.org/articles/PMC5884487?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0193544
URL الوصول: https://doaj.org/article/cc954aece4ce4624897dbe548cebd489
رقم الأكسشن: edsdoj.954aece4ce4624897dbe548cebd489
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0193544