According to results reported at the 40th Annual Meeting of the American Society of Clinical Oncology (ASCO), only half of the delivered dose of a commonly used chemotherapeutic agent may be activated in cancer patients.
The study, presented in a poster discussion session by Jason Fisher, a student at the University of Pittsburgh School of Engineering, analyzed data from 31 cancer patients given 30-minute infusions of gemcitabine to determine what percentage of the drug dose was associated with concentrations that exceeded the body's ability to activate the drug. He found that while approximately 50 percent of the gemcitabine dose was likely to be converted to active metabolites, the other 50 percent was likely to be inactivated, and as a result, possibly not contribute to a therapeutic effect.
"The purpose of this study was to use mathematics and engineering to try to improve cancer therapy," said Robert Parker, Ph.D., assistant professor of chemical engineering at the University of Pittsburgh and Mr. Fisher's undergraduate research project advisor. "We were surprised to find that about half of the dose of the drug administered might not be converted into an active form. The implication is that alternative schedules of gemcitabine infusions need to be evaluated carefully."
Dr. Parker explained that patients received gemcitabine doses of 650-950 mg/square meter and underwent pharmacokinetic sampling. Mathematical models were developed to calculate the time profile of drug concentrations in the body. "Although the study results demonstrate that administering gemcitabine as a 30-minute infusion resulted in approximately half of the dose being inactivated before it could be metabolized, the clinical implications of the data need to be explored further," said Dr. Parker.
The study was conducted on behalf of the Cancer and Leukemia Group B. Co-investigators of the study include Merrill J. Egorin, M.D., professor of medicine and pharmacology, University of Pittsburgh Cancer Institute; Mark J. Ratain, M.D., professor of medicine, University of Chicago; and Alan Venook, M.D., professor of medicine, University of California San Francisco. Support for the study was provided by Eli Lilly and Company.