Optimal Use of Irinotecan Still to be Determined

NASHVILLE, Tennessee—Irinotecan (Camptosar) has moved from scientific investigation to clinical application, but questions remain about its optimal use. These questions and related issues were outlined at the opening session of the Vanderbilt University Symposium, "Irinotecan: from Scientific Investigation to Clinical Application," by program chairman Mace L. Rothenberg, MD. Dr. Rothenberg is associate professor of medicine, Ingram Associate Professor of Cancer Research, at Vanderbilt University Medical Center in Nashville, Tennessee. The symposium was sponsored by Pharmacia Oncology.

"In preclinical models, irinotecan did not have to be administered at the maximum tolerated dose to achieve a maximum antitumor effect," Dr. Rothenberg stated. "The implication favors lower doses administered intermittently, but review of phase I/II trials shows that efficacy and toxicity are remarkably consistent across dosing schedules. How do we resolve this discrepancy?"

Complex Pharmacology

Irinotecan pharmacology is complex, and another important area of current research centers on the exploration of factors that contribute to the drug’s pharmacokinetic and pharmacodynamic variability. "We now know, for example, that thymidylate synthase upregulation does not predict clinical resistance to irinotecan," Dr. Rothenberg said.

Researchers are also looking for a reliable marker to predict response to irinotecan. Such a marker would be useful in guiding therapeutic decision making.

"Current challenges include gaining an understanding of the mechanism of cell death, the mechanisms of drug resistance, the pharmacogenetics of irinotecan, and the activity and pharmacology of irinotecan in central nervous system tumors," Dr. Rothenberg said.