Researchers from the Mayo Clinic Comprehensive Cancer Center and the Mayo Clinic Center for Individualized Medicine are studying the rare genetic condition called familial adenomatous polyposis, looking for potential ways to prevent colorectal cancer in the general population at an earlier, more treatable stage. The researchers’ findings were published by Samadder et al in the journal Gut.
“Colorectal cancer is the third most common cancer in the United States, and a precursor for this cancer is the development of polyps in the colon,” said first author Niloy Jewel Samadder, MD, a gastroenterologist at Mayo Clinic in Arizona. He explained that familial adenomatous polyposis is a rare genetic condition that begins with the development of hundreds of colorectal polyps that may eventually become cancerous.
“The biological pathway that leads to the development of polyps and colon cancer in patients with familial adenomatous polyposis is the same biological pathway as patients in the general population,” said Dr. Samadder. “Our trial looked at opportunities to use chemoprevention agents in patients with familial adenomatous polyposis to inhibit the development of precancerous polyps in the small bowel and colorectum.”
Researchers found that using the drug erlotinib, which blocks the EGFR cancer pathway, led to a 30% reduction in the number of polyps formed in the bowel of patients with familial adenomatous polyposis after 6 months of weekly treatments with the agent. Similar results were observed in subgroup analyses defined by participants with advanced duodenal polyposis (Spigelman 3) at baseline (about a 27% reduction); postintervention Spigelman stage was downstaged in 12% of the participants. Lower gastrointestinal polyp number also decreased after 6 months of intervention.
“We are now studying whether these findings can be expanded to the broader patient population that has either genetic or other risk factors that increase their chances of developing small bowel or colorectal cancer,” said Dr. Samadder.
The study authors concluded, “In this single-arm, multicenter trial of participants with familial adenomatous polyposis, [treatment with] erlotinib one time per week resulted in markedly lower duodenal polyp burden, and modestly reduced lower gastrointestinal polyp burden, after 6 months of intervention. While adverse events were still reported by nearly three-quarters of all participants, these events were generally lower grade and well tolerated. These findings support further investigation of erlotinib as an effective, acceptable cancer preventive agent for familial adenomatous polyposis–associated gastrointestinal polyposis.”
Disclosure: For full disclosures of the study authors, visit gut.bmj.com.
