A Randomized, Placebo-Controlled, Preoperative Trial of Allopurinol in Subjects with Colorectal Adenoma

• Published in: Cancer prevention research (Philadelphia, Pa.) Vol. 6; no. 2; pp. 74 - 81
• Main Authors: PUNTONI, Matteo, BRANCHI, Daniela, BANDELLONI, Roberto, TURBINO, Laura, MINETTI, Egle, MORI, Marco, SALVI, Sandra, BOCCARDO, Simona, GATTESCHI, Beatrice, BENELLI, Roberto, SONZOGNI, Angelica, DECENSI, Andrea, ARGUSTI, Alessandra, ZANARDI, Silvia, CROSTA, Cristiano, MERONI, Emanuele, MUNIZZI, Francesco, MICHETTI, Paolo, COCCIA, Gianni, DE ROBERTO, Giuseppe
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-02-2013
• Subjects: Adenoma - drug therapy; Adenoma - surgery; Adenomatous Polyps - drug therapy; Adenomatous Polyps - surgery; Aged; Allopurinol - administration & dosage; Antimetabolites, Antineoplastic - administration & dosage; Biological and medical sciences; Chemotherapy, Adjuvant; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - surgery; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Male; Medical sciences; Middle Aged; Miscellaneous; Placebos; Preoperative Care; Preoperative Period; Prevention and actions; Public health. Hygiene; Public health. Hygiene-occupational medicine; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Human; Rectal disease; Hypouricemic agent; Enzyme; Allopurinol; Enzyme inhibitor; Randomized controlled trial; Colonic disease; Pyrazolopyrimidine derivatives; Colorectal adenoma; Randomization; Placebo; Digestive diseases; Intestinal disease; Xanthine oxidase; Clinical trial; Oxidoreductases; Benign neoplasm; Preoperative
• ISSN: 1940-6207; 1940-6215
• DOI: 10.1158/1940-6207.CAPR-12-0249

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 used as antigout agent, has been shown to increase survival of patients with advanced CRC and to reduce CRC incidence in long-term gout users in epidemiologic studies. We conducted a randomized, double-blind, placebo-controlled preoperative trial in subjects with colorectal adenomatous polyps to assess the activity of allopurinol on biomarkers of colorectal carcinogenesis. 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 (100 mg or 300 mg) and treated for four weeks before polyp removal. Change of Ki-67 labeling index in adenomatous tissue was the primary endpoint. Secondary endpoints were the immunohistochemical (IHC) expression of NF-κB, β-catenin, topoisomerase-II-α, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in adenomatous polyps and normal adjacent colonic tissue. Compared with placebo, Ki-67 levels were not significantly modulated by allopurinol, whereas β-catenin and NF-κB expression levels decreased significantly in adenomatous tissue, with a mean change from baseline of -10.6%, 95% confidence interval (CI), -20.5 to -0.7, and -8.1%, 95% CI, -22.7 to 6.5, respectively. NF-κB 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-κB expression in normal tissue. Allopurinol can inhibit biomarkers of oxidative activation in colon adenomatous polyps and normal adjacent tissue. Further studies should define its potential chemopreventive activity.