Allopurinol may decrease risk for colorectal adenoma progression
Allopurinol ( Zyloprim ), a relatively inexpensive anti-gout medication that has been on the market for more than 20 years, may have some activity against colorectal adenomas, according to data presented at the Ninth Annual AACR Frontiers in Cancer Prevention Research Conference.
Specifically, the presence of a colorectal tumor tissue biomarker, Ki67, was markedly decreased in the preliminary results of a study of patients with colorectal polyps assigned to take Allopurinol.
In colorectal tumor tissue there are high levels of ROM, or reactive oxygen metabolites. These ROMs are thought to be important for development of tumor tissue and carcinogenesis. It is known that ROMs activate crucial processes involved in cell growth, and in processes that inhibit programmed cell death, one of the main mechanisms involved in cancer control.
Therefore, researchers are testing the effect of ROM scavengers, such as Allopurinol, to measure their effects on chemoprevention. According to Andrea De Censi at Galliera Hospital ( Genoa, Italy ), previous research from a large case-control study conducted in Israel showed that patients under chronic Allopurinol use for gout had a lower risk for colorectal cancer than a matched control group not using Allopurinol.
In the current study, De Censi and colleagues conducted a phase I/II double-blind, placebo-controlled trial of patients with colorectal adenomatous polyps. Between 2006 and 2010, 73 patients were enrolled and assigned placebo or either a 100-mg or 300-mg dose of Allopurinol for four to six weeks prior to removal of polyps.
They collected normal and adenomatous tissue samples and measured changes in the biomarker Ki67 in the normal tissue and the adenomatous tissue to measure the effect of Allopurinol. At an interim analysis, conducted in November of 2008, only three mild adverse gastrointestinal events had occurred, confirming the high safety profile of Allopurinol.
Tissue analysis in the first 13 patients indicated that levels of Ki67 in normal tissue had doubled in patients taking placebo, but had only increased by 5% in patients taking either dose of Allopurinol.
In adenoma tissue, levels of Ki67 increased by 70% in patients taking placebo compared with only 6% in patients taking 100 mg Allopurinol and 12% in patients taking 300 mg Allopurinol.
The findings need to be confirmed on a larger number of subjects. However, if the positive trend noted on Ki67 is confirmed, Allopurinol has some activity against colon carcinogenesis that may explain the favorable trend noted in the epidemiological studies. ( Xagena )
Source: American Association for Cancer Research, 2010
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