SAN FRANCISCOSt. John’s wort, a popular herbal preparation that is commonly used to treat depression and other illnesses, alters the metabolism of the anticancer agent irinotecan(Drug information on irinotecan) (Camptosar), according to the results of a study presented at the 93rd Annual Meeting of the American Association for Cancer Research (AACR abstract 2443).
Irinotecan, a prodrug of the topoisomerase I inhibitor SN-38, is converted to APC and other inactive compounds via the cytochrome P450 isozyme 3A4 (CYP3A4) pathway. St. John’s wort induces activity of CYP3A4, thus modulating irinotecan metabolism.
"About 50% of all kinds of drugs, including anticancer agents, are metabolized by CYP3A4," said Ron Mathijssen, MD, of the Department of Medical Oncology, Rotterdam Cancer Institute, The Netherlands. "So, the problem is potentially more widespread than this single study shows."
St. John’s wort is available without a prescription in North America and Europe, and sales of this herbal product have increased dramatically over the past decade. According to Dr. Mathijssen, sales of St. John’s wort totaled $6 billion in 1998.
In this randomized crossover trial, five colorectal cancer patients were treated with two courses, 3 weeks apart, of irinotecan given as a 90-minute intravenous infusion at a dose of 350 mg/m². During one course, the patients were treated only with irinotecan; during the other course, they were also given a 21-day regimen of 300 mg of St. John’s wort, taken three times daily and started 14 days before the irinotecan infusion.
Some patients received monotherapy during the first course and cotreatment during the second course and some the reverse order.
Blood samples were taken periodically during the 3 weeks following the infusion, and levels of irinotecan, SN-38, and metabolites of these two compounds were measured by reversed-phase high-performance liquid chromatography with fluo-rescence detection.