Role of dietary polyamines in a phase III clinical trial of difluoromethylornithine (DFMO) and sulindac for prevention of sporadic colorectal adenomas
Menée sur 188 patients inclus dans un essai clinique de phase III évaluant un traitement combinant la difluorométhylornithine et le sulindac, un anti-inflammatoire non stéroïdien, pour prévenir le risque d'adénome colorectal, cette étude analyse la relation entre un régime alimentaire favorisant la synthèse endogène de polyamines et l'efficacité du traitement
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. Conclusion : 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.