A randomized, placebo controlled, pre-operative trial of allopurinol in subjects with colorectal adenoma
Mené sur 73 patients présentant des adénomes colorectaux, cet essai randomisé pré-opératoire évalue l'effet de l'allopurinol, un médicament hypo-uricémiant, sur les niveaux d'expression de biomarqueurs de la carcinogenèse du côlon ou du rectum
Background: Inflammation and oxidative stress play a crucial role in the development of colorectal cancer (CRC) and interference with these mechanisms represents a strategy in CRC chemoprevention. Allopurinol, a safe molecular scavenger largely employed as anti-gout agent, has been shown to increase survival of patients with advanced CRC and to reduce CRC incidence in long-term gout users in epidemiological studies. We conducted a randomized, double-blind, placebo-controlled pre-operative trial in subjects with colorectal adenomatous polyps to assess the activity of allopurinol on biomarkers of colorectal carcinogenesis. Methods: After complete colonoscopy and biopsy of the index polyp, 73 subjects with colorectal adenomas were assigned to either placebo or one of two doses of allopurinol (100mg or 300mg) and treated for 4 weeks before polyp removal. Change of Ki-67 labeling index in adenomatous tissue was the primary endpoint. Secondary endpoints were the IHC expression of NF-kβ and β-catenin, Topoisomerase-II-α and TUNEL in adenomatous polyps and normal adjacent colonic tissue. Results: Compared with placebo, Ki-67 levels were not significantly modulated by allopurinol, whereas β-catenin and NF-kβ expression levels decreased significantly in adenomatous tissue, with a mean change from baseline of-10.6%, 95%CI, -20.5 to -0.7, and -8.1%, 95%CI, -22.7 to 6.5, respectively. NF-kβ also decreased significantly in normal adjacent tissue (-16.4%; 95% CI, -29.0 to -3.8). No dose-response relationship was noted, except for NF-kβ expression in normal tissue. Conclusions: Allopurinol can inhibit biomarkers of oxidative activation in colon adenomatous polyps and normal adjacent tissue. Further studies should define its potential chemopreventive activity.