Chemoprevention of gastrointestinal cancer

Digestive tract cancers have been the subject of considerable research regarding chemopreventive interventions, arguably more than for any other organ system. Although there are essentially no promising leads for pancreatic cancer, there are indications that chemoprevention of other digestive tract malignancies might actually be possible.

The colorectum is the most studied digestive tract organ regarding chemoprevention [1]. Supplementation with relatively high doses of beta carotene, alpha tocopherol or ascorbic acid has not reduced risk of colorectal cancer or adenomas [1], [2]. However, in a secondary analysis of a small skin cancer prevention trial, one “antioxidant,” selenium, was apparently protective against colorectal cancer. Trials of cereal fiber supplements have showed no substantial effect on adenoma risk, and ursodeoxycholic acid seems at best to provide limited benefits. Emerging data regarding folate are also discouraging.

On the other hand, at least two interventions do appear to have chemopreventive efficacy in the colorectum. Clinical trials have shown that calcium supplementation reduces the risk of adenomas, and epidemiological data suggest that there is a similar effect for colorectal cancer itself. Extensive epidemiological and clinical trial data also support the efficacy of non-steroidal anti-inflammatory drugs.

For cancers of the upper luminal GI tract, observational studies suggest that NSAIDs have promise, but the only clinical trial that has reported relevant data (for the esophagus) was negative [1]. H. Pylori eradication with antibiotics shows suggestions of benefit for carcinoma of the stomach, but the findings have not been consistent [1]. In one trial, supplementation with a combination of beta carotene, vitamin E, and selenium reduced risk of stomach cancer. Other agents, including nutrient mixtures and Asian traditional medicines have been tested in clinical trials focusing on the stomach or esophagus, but the findings have not been replicated [1].

Although definitive clinical trial data are still lacking, it seems likely that HBV vaccination will decrease liver cancer risk [1]. Interferon also may decrease cancer risk in patients with cirrhosis and hepatitis C [1]. Several other agents have been tested in trials, sometimes with positive results, but the findings remain isolated or have only been conducted in an adjuvant setting [1].

The interpretation of many of the chemoprevention trials is not straightforward. The vast majority of the studies have studied patients with a history of pre-invasive lesions, and the endpoints have typically been progression/regression or recurrence of the pre-invasive lesions, not cancer. This strategy focuses on the pre-invasive stages of carcinogenesis, and the results may not apply to cancer itself. For example, the small adenomas that comprise most of the endpoints in colorectal studies are themselves not particularly aggressive, and more prolonged intervention than is usually sustained in these trials might be required for a beneficial impact to emerge. Some of the trials used synthetic agents in high doses. Nonetheless, recent trials have helped establish that some agents can interfere with carcinogenesis in the large bowel, raising hopes for effective chemoprevention.

In summary, it is likely that chemoprevention of several gastrointestinal cancers will be possible. Further research will have to assess whether the interventions that reduce risk are cost effective.