Mayo researchers will present these findings at the 2005 American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Fla. The three drugs involved in their investigation are irinotecan, oxaliplatin and capecitabine, and each is individually approved by the Food and Drug Administration (FDA) for the treatment of cancer.
"By using the genetic test prior to the start of chemotherapy, we demonstrated that you can put these drugs together safely," says Mayo Clinic medical oncologist Matthew Goetz, M.D., the study's lead investigator. Co-investigator and oncology researcher Matthew Ames, Ph.D., adds, "We defined different patient populations based on a specific genetic variant to provide a better understanding of how this three-drug regimen will affect individual patients."
Significance of the Mayo Clinic Research
Of the three drugs, irinotecan can be particularly toxic for some patients. Despite the antitumor benefit of each drug, researchers have had difficulty putting the drugs together because the toxicity can be lethal.
The genetic test detects a change in the DNA of a gene that encodes for a protein involved in the metabolism of irinotecan. The test gives scientists advance knowledge of the individual risk for toxicity from irinotecan. As a result, scientists are able to tailor this chemotherapy regimen to the individual, thus reducing toxicity. 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.
"In the past, a physician knew that the genetic test could predict a higher risk for irinotecan-related toxicity," says Dr. Goetz, "but no one knew what to do with this information with regard to dosing, both for irinotecan and drugs combined with irinotecan. Our study is the first to demonstrate that when you give these drugs in combination, a patient's individual genetic makeup affects the tolerable dose."
The Next Step
Having met the goal of using the genetic test to dose patients, Mayo Clinic researchers will test this combination therapy against specific cancers.
Collaboration and Support
In addition to Drs. Goetz and Ames, the Mayo Clinic research team included Stephanie Safgren; Joel Reid, Ph.D.; Sumithra Mandrekar, Ph.D.; Alfred Furth; Alex Adjei, M.D., Ph.D.; Axel Grothey, M.D.; Charles Erlichman, M.D.; Joseph Rubin, M.D.; and Mary Kuffel. Richard Goldberg, M.D., of the University of North Carolina, Chapel Hill, N.C., also collaborated on this study.
DISCLOSURE: This study was supported by grants from the National Cancer Institute (NCI).