Easing the Irinotecan Side Effect

Irinotecan (also called CPT-11 and/or Camptosar) is often used to treat advanced colorectal cancer. But it causes diarrhea in most patients–severe in 30 percent—that often limits the dose a patient can tolerate.

Now researchers at the University of North Carolina at Chapel Hill have found a way to block one specific troublemaking enzyme thought to play a big role in causing the diarrhea.

Irinotecan is complicated: After it has killed tumor cells, the drug is filtered out of the bloodstream by the liver, where it’s changed to an inactive compound and discharged into the intestine to be excreted. But in the intestine, the drug can be reactivated by an enzyme that is made by bacteria that normally live in the gut. The reactivated toxic drug then damages the intestinal lining—leading to severe diarrhea.

Matthew Redinbo, PhD, and his team wanted to block the enzyme that reactivates irinotecan, yet not kill the intestinal bacteria, because it’s vital for digestion, vitamin manufacturing and fighting infections. Sorting through a database of 10,000 chemical compounds, the research team found four chemicals that, at least in a test tube, blocked the enzyme without harming the bacteria. They tested one compound in mice: Those given irinotecan plus the compound had far less severe diarrhea than mice given just irinotecan.

An accompanying Science editorial noted that this experiment is only the first step in a long process of test tube and then animal testing, before human testing could even begin. But the editors also noted that, while much research is aimed at finding new treatments, this kind of research can vastly improve current anticancer drugs.

Addendum: The lead researcher, Redinbo, initially began the research after seeing a friend suffer through therapy and ultimately die from colorectal cancer. Only late in the process did he discover that another team member shared a similar experience. “As scientists, our [personal] experiences can have a profound effect on our work,” Redinbo said.

Source: Science (5 November 2010) and Medical News Today (Nov. 6)

Disclosure:  The Colorectal Cancer Coalition has received funding from Pfizer, the company that manufactures Camptosar, in the form of unrestricted educational grants.  The Coalition has ultimate authority over website content.