Interferon Significantly Affects Metabolism of Other Drugs Given to Cancer Patients

Given to Cancer Patients Cancer patients undergoing therapy with interferonalfa-2b (IFN-a-2b [Intron A]) are possibly being overmedicated with the narcotics and antidepressants commonly administered with this agent, according to a University of Pittsburgh Cancer Institute (UPCI) study. Results of the study, presented at the 35th annual meeting of the American Society of Clinical Oncology (ASCO), showed that interferon-alfa-2b significantly depresses the activity of liver enzymes that break down these drugs.

Two Important Drug-Metabolizing Enzymes Affected

The study focused on patients who were treated surgically for melanoma and received high-dose interferon-alfa-2b to prevent a recurrence of disease. Six patients got a “cocktail” of chemicals, each of which is metabolized by a different enzyme in the family of CYP450 enzymes. Results of the study showed that interferon-alfa-2b depressed the activity of two enzymes, CYP1A2 and CYP2E1, by 30%. These enzymes are important in metabolizing the narcotics and antidepressants given to relieve the side effects of interferon-alfa-2b therapy.

“What these results tell us is that we are probably intoxicating patients when we use narcotics and antidepressants together with [interferons],” said John Kirkwood, MD, professor of medicine and director of the UPCI’s Melanoma Center. “The CYP enzymes in IFN-a-2b-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 IFN-a-2b therapy.”

Dr. Kirkwood, Mohammed Islam, MD, a research associate at UPCI who presented the study, and Reginald Frye, PharmD, of the University of Pittsburgh School of Pharmacy, are extending their studies to other CYP enzymes involved in drug metabolism.