ATLANTA, May 17 -- Cancer patients undergoing therapy with interferon alfa 2b (IFNa2b) could be overmedicated with narcotics and antidepressants commonly administered with this agent, according to a University of Pittsburgh Cancer Institute (UPCI) study showing that IFNa2b significantly depresses the activity of internal enzymes that break down these drugs. Results of the study, which have broad implications for using IFNa2b, are being presented Monday, May 17, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Atlanta.
Interferons are biological response modifiers produced naturally by the body to fight infections and tumors. IFNa2b is manufactured for use in cancer treatment studies, and it can cause flu-like symptoms and depression in people receiving it.
The study focused on patients who were surgically treated for melanoma and receiving high-dose IFNa2b to prevent recurrence of the disease. Six patients got a "cocktail" of chemicals, each of which is metabolized by a different enzyme in the family of CYP450 enzymes. CYP450 enzymes operate within the liver. Results of the study showed that IFNa2b depressed the activity of two enzymes, CYP1A2 and CYP2E1, by 30 percent. These enzymes are important in metabolizing narcotics and antidepressants given to relieve side effects of IFNa2b therapy.
"What these results tell us is that we are probably intoxicating patients when we use narcotics and antidepressants together with IFNs," said John Kirkwood, M.D., professor of medicine and director of the UPCI's Melanoma Center. "The CYP enzymes in IFNa2b-treated patients simply can't metabolize these drugs effectively, so we could probably reduce the amount of these medications we're administering during the course of IFNa2b therapy."
Dr. Kirkwood and Mohammed Islam, M.D., a research associate at UPCI who is presenting this study at the ASCO meeting, are extending their studies to other CYP enzymes involved in drug metabolism with Reginald Frye, Pharm.D., Ph.D., of the University of Pittsburgh School of Pharmacy.
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