Role of obesity in a randomized placebo-controlled trial of difluoromethylornithine (DFMO) + sulindac for the prevention of sporadic colorectal adenomas.
BACKGROUND
Chemoprevention with the polyamine-inhibitory regimen difluoromethylornithine (DFMO) + sulindac markedly reduces risk of recurrent adenoma in colorectal adenoma patients. Obesity is associated with risk of colorectal adenoma and colorectal cancer. This study investigates how obesity influences risk of recurrent adenoma after prolonged treatment with DFMO + sulindac versus placebo.


METHODS
Our analysis included subjects enrolled in the phase III colorectal adenoma prevention clinical trial investigating DFMO + sulindac versus placebo. Patients were classified by obesity (body mass index, BMI ≥ 30 kg/m(2)) status at baseline. Pearson χ(2) statistic and Mann-Whitney U test were used to compare baseline characteristics, including rectal tissue polyamine levels. Log-binomial regression analysis was used to determine the risk ratio (RR) of recurrent adenomas, adjusted for covariates and an interaction term for obesity and treatment.


RESULTS
The final analytic cohort was comprised of 267 patients. In separate regression models, the risk of adenoma recurrence after treatment compared to placebo was similar for obese (RR = 0.32, 95 % CI 15-71) and non-obese patients (RR = 0.27, 95 % CI 15-49). No significant interaction was detected between obesity, treatment, and risk of colorectal adenoma in the full regression model (p                            (interaction) = 0.91).


CONCLUSIONS
Obesity does not substantially modify the colorectal adenoma risk reduction ascribed to DFMO + sulindac versus placebo.
Chao Family Comprehensive Cancer Center, University of California, Irvine, CA 92697, USA. jzell@uci.edu
Jason A
JA
Zell
Bruce S
BS
Lin
Nikki
N
Madson
Christine E
CE
McLaren
Eugene W
EW
Gerner
Frank L
FL
Meyskens
D000236:Adenoma / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D004311:Double-Blind Method; D000518:Eflornithine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism*; D015990:Placebo Effect; D011073:Polyamines / Q000378:metabolism; D012044:Regression Analysis; D013467:Sulindac / Q000008:administration & dosage; D016896:Treatment Outcome
D011073:Polyamines; D013467:Sulindac; D000518:Eflornithine