For some colon cancer patients receiving a common chemotherapy, a variation in their DNA results in a lowered white blood cell count—an outcome that could lead to death—but a new test can identify the patients before treatment even starts. Chemotherapy with irinotecan has been shown to improve survival rates, scientists say, but for one in 10 patients with metastatic colon cancer, the treatment could lead to a high risk of bacterial infection and possible death. That’s why a new pretreatment pharmacogenetic test identifying genetic variations could help pinpoint those patients who need lower doses of the drug, say researchers at Weill Cornell Medical College.

 

“Pharmacogenetic testing is a relatively new treatment innovation that may prove to be a valuable tool for clinicians as they develop personalized treatments for cancer patients to minimize side effects while maintaining outcomes,” says lead author Heather Taffet Gold, assistant professor in the Division of Health Policy in the Department of Public Health at Weill Cornell Medical College. “Our study points to significant potential benefits for pretreatment pharmacogenetic testing for metastatic colorectal cancer, but remains to be verified by clinical research.”

 

However, the test is only beneficial if lower-dose treatments are found to be just as effective as normal doses, according to the study, appearing in the journal Cancer.

 

If the lower dose is as effective, the test could prevent many cases of severe neutropenia, an abnormally low count of an important type of white blood cell known as neutrophils. It would also mean better life expectancy and lower cost of care, the researchers note.

 

“This study is an important example of how the combined use of cost-effectiveness analysis and pharmacogenetic testing can improve treatment outcomes,” says Alvin I. Mushlin, professor and chairman of the Weill Cornell Department of Public Health. “Both methods are becoming increasingly integral to the advancement of evidence-based medicine.”

 

The study used a computer simulation model of hypothetical patients treated with the irinotecan chemotherapy for metastatic colon cancer. The model assumed that under usual care, patients received a full dose of irinotecan. In individuals identified as having a genetic variation, the irinotecan dosage was reduced by 25 percent—the amount recommended by the U.S. Food and Drug Administration to minimize cases of neutropenia.

The team says more research needs to be done comparing genetic testing and cost-effective treatments. The scientists recommend devoting up to $22 million to further study the risks and benefits of dose reductions based on genetic tests, says senior author Bruce Schackman, associate professor of Public Health and chief of the Division of Health Policy in the Department of Public Health at Weill Cornell Medical College.

 

“Cost-effectiveness evaluations of pharmacogenetic tests can provide important insights into both the clinical and economic value of these new treatment paradigms, but few of these types of studies have been conducted,” Schackman says. “Importantly, these studies also allow us to define in economic terms the value of additional comparative effectiveness research.”