title: Role of dietary polyamines in a phase III clinical trial of difluoromethylornithine (DFMO) and sulindac for prevention of sporadic colorectal adenomas.
abstract: BACKGROUND
  The polyamine-inhibitory regimen difluoromethylornithine (DFMO)+sulindac has marked efficacy in preventing metachronous colorectal adenomas. Polyamines are synthesised endogenously and obtained from dietary sources. Here we investigate dietary polyamine intake and outcomes in the DFMO+sulindac colorectal adenoma prevention trial.
  
  
  METHODS
  Dietary polyamine data were available for 188 of 267 patients completing the study. Total dietary polyamine content was derived by the sum of dietary putrescine, spermine and spermidine values and categorised into two groups: highest (>75-100%) vs the lower three quartiles (0-25, 25-50 and 50-75%). Baseline tissue polyamine concentration and ODC1 genotype were determined. Logistic regression models were used for risk estimation.
  
  
  RESULTS
  A significant interaction was detected between dietary polyamine group and treatment with regard to adenoma recurrence (P=0.012). Significant metachronous adenoma risk reduction was observed after DFMO+sulindac treatment in dietary polyamine quartiles 1-3 (risk ratio (RR) 0.19; 95% confidence interval (CI) 0.08-0.42; P<0.0001) but not in quartile 4 (RR 1.51; 95% CI 0.53-4.29; P=0.44). However, a lower number of events in the placebo group within dietary quartile 4 confound the aforementioned risk estimates.
  
  
  CONCLUSIONS
  These preliminary findings reveal complex relationships between diet and therapeutic prevention, and they support further clinical trial-based investigations where the dietary intervention itself is controlled.
authors: Chao Family Comprehensive Cancer Center, University of California, Irvine, CA 92697, USA.
authors: K P
authors: KP
authors: Raj
authors: J A
authors: JA
authors: Zell
authors: C L
authors: CL
authors: Rock
authors: C E
authors: CE
authors: McLaren
authors: C
authors: C
authors: Zoumas-Morse
authors: E W
authors: EW
authors: Gerner
authors: F L
authors: FL
authors: Meyskens
mesh_terms: D000236:Adenoma / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D004032:Diet; D000518:Eflornithine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D011073:Polyamines / Q000008:administration & dosage*; D011379:Prognosis; D013467:Sulindac / Q000008:administration & dosage; D015996:Survival Rate
chemical_list: D011073:Polyamines; D013467:Sulindac; D000518:Eflornithine