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St. John’s Wort May Limit Effectiveness of Chemotherapy

St. John’s Wort May Limit Effectiveness of Chemotherapy

SAN FRANCISCO—St. 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 (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.

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