Obesity Does Not Affect DFMO + sulindac Chemoprevention of Colorectal Adenomas

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(ChemotherapyAdvisor) – Patient obesity does not impact the anti-colorectal adenoma chemopreventive benefits of polyamine-inhibitory difluoromethylornithine (DFMO) + sulindac therapy, according to a study published in Cancer Causes & Control.

“Obesity does not substantially modify the colorectal adenoma (CRA) risk reduction ascribed to DFMO+sulindac versus placebo,” reported Jason A. Zell, DO, MPH, of the Chao Family Comprehensive Cancer Center at the University of California, Irvine.

Obesity increases the risk of colorectal adenoma and cancer, and animal studies have found polyamine metabolism and polyamine inhibition to be associated with weight gain and adipose tissue, suggesting potential associations between polyamine colorectal carcinogenesis and energy balance or adiposity.

The authors analyzed data from a previously-reported Phase III colorectal adenoma prevention trial to compare baseline rectal tissue polyamine levels and colorectal adnoma recurrence among obese (body mass index ≥ 30 kg/m2 at baseline) and non-obese participants.

Risk ratios (RRs) for 267 participants were 0.32 (95% CI, 15-71) for obese patients and 0.27 (CI, 15-49) for non-obese patient; P=0.91, n.s.), the authors reported.

“This has impolications for therapeutic prevention of CRAs, since a key goal of cancer prevention clinical trials is to refine the risk:benefit, and risk:risk profile of chemopreventive agents,” the authors wrote. “The large risk reduction afforded to CRA patients receiving DFMO+sulindac as compared to placebo in the parent trial appears to occur regardless of whether or not patients are obese.”

Nevertheless, lifestyle modifications to reduce the risk of colorectal cancer, including physical activity, obesity control, and dietary modifications, remain important, the authors emphasized.

Two of the study's authors have ownership interests in Cancer Prevention Pharmaceuticals, LLC (a company developing chemopreventive agents for patients at high risk of colorectal and other cancers), the authors reported.


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