Abstract

: The long-range objective of our work is to develop safe and effective drugs to prevent colon cancer, which is the fourth most common incident cancer in America with over 58,000 people dying of the disease in the year 2000.
Our specific aims i n this application are: 1.To conduct a randomized, double-blind placebo-controlled phase III clinical chemoprevention trial of the combination of DFMO plus sulindac to decrease the rate of new adenomatous polyp formation. 2. To correlate the effects of the combination on polyamine and prostaglandin contents in the flat mucosa to the rate of adenoma formation. 3. To determine the rate of side effects in patients randomized to the combination therapy over the course of the intervention. The major objectives of this investigation are to reduce the recurrence rate of adenomatous colonic polyps without producing toxicity greater than that seen in the placebo group. The overall goal of our work is to develop safe combinations of chemoprevention agents that can be used in the practice setting and complement current surveillance efforts.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA088078-03
Application #
6789437
Study Section
Subcommittee G - Education (NCI)
Program Officer
Richmond, Ellen S
Project Start
2002-09-30
Project End
2007-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
3
Fiscal Year
2004
Total Cost
$797,316
Indirect Cost

  Institution

Name
University of California Irvine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697

  Publications

Raj, K P; Zell, J A; Rock, C L et al. (2013) Role of dietary polyamines in a phase III clinical trial of difluoromethylornithine (DFMO) and sulindac for prevention of sporadic colorectal adenomas. Br J Cancer 108:512-8
Rial, Nathaniel S; Zell, Jason A; Cohen, Alfred M et al. (2012) Clinical end points for developing pharmaceuticals to manage patients with a sporadic or genetic risk of colorectal cancer. Expert Rev Gastroenterol Hepatol 6:507-17
Laukaitis, Christina M; Erdman, Steven H; Gerner, Eugene W (2012) Chemoprevention in patients with genetic risk of colorectal cancers. Colorectal Cancer 1:225-240
Zell, Jason A; Lin, Bruce S; Madson, Nikki et al. (2012) Role of obesity in a randomized placebo-controlled trial of difluoromethylornithine (DFMO) + sulindac for the prevention of sporadic colorectal adenomas. Cancer Causes Control 23:1739-44
Laukaitis, Christina M; Gerner, Eugene W (2011) DFMO: targeted risk reduction therapy for colorectal neoplasia. Best Pract Res Clin Gastroenterol 25:495-506
Zell, Jason A; McLaren, Christine E; Chen, Wen-Pin et al. (2010) Ornithine decarboxylase-1 polymorphism, chemoprevention with eflornithine and sulindac, and outcomes among colorectal adenoma patients. J Natl Cancer Inst 102:1513-6
Thompson, Patricia A; Wertheim, Betsy C; Zell, Jason A et al. (2010) Levels of rectal mucosal polyamines and prostaglandin E2 predict ability of DFMO and sulindac to prevent colorectal adenoma. Gastroenterology 139:797-805, 805.e1
Gerner, Eugene W; Meyskens Jr, Frank L (2009) Combination chemoprevention for colon cancer targeting polyamine synthesis and inflammation. Clin Cancer Res 15:758-61
Zell, Jason A; Pelot, Daniel; Chen, Wen-Pin et al. (2009) Risk of cardiovascular events in a randomized placebo-controlled, double-blind trial of difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas. Cancer Prev Res (Phila) 2:209-12
Meyskens Jr, Frank L; McLaren, Christine E; Pelot, Daniel et al. (2008) Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial. Cancer Prev Res (Phila) 1:32-8

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