Cancer Therapy
Mayo Clinic has validated and will offer to patients worldwide a test that enables its laboratory to determine through genetic screening which patients are likely to have a serious adverse reaction to irinotecan hydrochloride (Camptosar ), a key component of the standard first-line treatment for advanced colon cancer and rectal cancer.
The UGT1A1 technology, the basis for the diagnostic test, was discovered by Mark Ratain, M.D., and colleagues at the University of Chicago. The UGT1A1 test detects a change in the DNA of a gene that encodes for a protein involved in the metabolism of irinotecan, giving doctors advance knowledge of the individual risk for toxicity from irinotecan. This kind of customized dosing approach based on a person's genetic makeup is known as pharmacogenomics and is the newest frontier of 21st century medicine.
The test is being offered to patients nationwide through Mayo Medical Laboratories (MML), Mayo Clinic's reference laboratory, and via a sublicense providing the rights under the University of Chicago patents to Third Wave Technologies, Madison, Wis. Third Wave (Nasdaq: TWTI) received Food and Drug Administration, (FDA) approval for its UGT1A1 test kit in August. The just-finalized license agreements have cleared the way for the testing to be offered broadly and nonexclusively.
"Interest in individualized drug therapy in general, and in oncology specifically, has grown rapidly since the FDA's approval of the UGT1A1 assay," says Lawrence Lesko, Ph.D., director of the FDA's Office of Clinical Pharmacology and Biopharmaceutics in the Center for Drug Evaluation and Research. "It is gratifying to see world- leading organizations like Mayo Clinic embrace this important development in personalized medicine, as this assay provides physicians and their patients with significant adjunctive information on the proper dosage of drugs like irinotecan metabolized and cleared by the UGT1A1 pathway. Information on the UGT1A1 genotype, and other important patient factors, should be an integral part of guiding health professionals on dosing of medications like irinotecan and optimizing the benefit/risk ratio."
"We believe this is the first test to bring the benefits of pharmacogenomics to a large population of cancer patients," says Mayo Clinic medical oncologist Matthew Goetz, M.D. "Irinotecan is an important treatment approved by the FDA for patients with colon and rectal cancers, but its side effects can be dangerous or even lethal in up to 30 percent of the population."
In his laboratory, Mayo Clinic scientist Matthew Ames, Ph.D., has been developing and applying pharmacogenomic tests in cancer clinical trials in collaboration with Dr. Goetz. Dr. Ames adds, "Previous genetic tests have involved relatively rare diseases, or mutations that affect drug metabolism in a tiny fraction of patients. In contrast, this pharmacogenomic test affects a large proportion of patients treated with irinotecan, an important component of the best care available to patients with colorectal cancer."
Colorectal cancer is the fourth most commonly diagnosed cancer in the United States., with over 145,000 new cases per year. It accounts for nearly 60,000 deaths per year in the United States.
Published studies in the medical literature have estimated that each year 100,000 U.S. patients die due to adverse drug reactions. The UGT1A1 test is part of a growing list of pharmacogenomic tests Mayo offers to help physicians personalize treatment options. Pharmacogenomics is the practice of individualizing drug selection and dosing based on a person's genomic makeup; pharmacogenomic testing can help determine which patients should receive which doses of which medications to avoid adverse drug reactions.
"This test helps physicians prescribe the right drug at the right dosage for their patients," says Dennis O'Kane, Ph.D., the Mayo Clinic scientist who led Mayo's development of the screening test. "Patients susceptible to side effects may be able to take the drug, but at a much lower dose. At a minimum, it will alert physicians which patients need to be watched extremely closely for signs of life-threatening side effects."
Dr. Goetz says the test may not only prevent life-threatening reactions in patients unable to normally metabolize the drug, but it may also lead to a more accurate determination of the dosing of irinotecan in patients with normal levels of UGT1A1. "When we test a drug for FDA approval, we look for a dose that yields benefits while minimizing toxicity," he explains. "In the case of irinotecan and UGT1A1, patients with normal levels of the UGT1A1 enzyme may be receiving subtherapeutic doses of irinotecan and drugs administered together with it. We have several clinical trials under way to use the UGT1A1 test to determine the best way to dose irinotecan chemotherapy while minimizing the risk of side effects in each of the genomic subgroups."
Dr. Goetz adds that the application of this test for patients with colon and rectal cancer may only be the beginning. "Irinotecan also is being tested and used for other cancers, such as cancers of the GI tract, as well as lung and breast carcinoma," he say. Dr. Ames notes, "The UGT1A1 pathway also is important in metabolizing other medications, so I expect the test may be useful for other drugs, also metabolized by UGT1A1."
The Department of Laboratory Medicine and Pathology at Mayo Clinic maintains an active diagnostic test development program. These activities also incorporate discoveries made elsewhere, such as the UGT1A1 patents from the University of Chicago.
Mayo offers these proven diagnostic technologies to more than 5,000 health care institutions around the world through MML.
Working with the Department of Oncology at Mayo Clinic, the Department of Laboratory Medicine and Pathology refined and validated this gene sequencing test for use by its physicians, and will offer it to other health care organizations through MML. Mayo acquired an exclusive license to the UGT1A1 technology from the University of Chicago, which includes the right to sublicense the test, and will actively pursue agreements with other academic medical centers, laboratories, diagnostic test companies and pharmaceutical companies to ensure that patients everywhere have access to this important screening test.
Revenue from MML testing and technology licensing is used to support medical education and research at Mayo Clinic. Camptosar is a Pfizer product.
Comments
Post new comment