St. John's wort (Hypericum perforatum L.) is widely used to treat mild to moderate forms of depression. Past studies have suggested that the compound increases levels of CYP3A4, an enzyme involved in drug metabolism. The enzyme inactivates the colorectal cancer chemotherapy drug irinotecan.

To examine the interaction between St. John's wort's and irinotecan, Ron H. J. Mathijssen, M.D., and Alex Sparreboom, Ph.D., of the Department of Medical Oncology at the Erasmus MC-Daniel den Hoed Cancer Center, and their colleagues treated five patients with irinotecan alone or in combination with St. John's wort.

At the end of the study, blood levels of SN-38 (the active metabolite of irinotecan) were 42% lower in patients receiving irinotecan and St. John's wort than when the patients received irinotecan alone. Detoxification of the drug to other known metabolites also decreased with St. John's wort.

"Our findings suggest that irinotecan metabolism and toxicity are altered by [St. John's wort] and that the two agents cannot be given safely in combination without compromising overall antitumor activity," the authors write.

They note that their results may have implications for other anticancer drugs metabolized by CYP3A4, such as the taxanes (paclitaxel). Combining these drugs with St. John's wort may make it necessary to increase drug dosage to achieve the optimal pharmacologic effect. "Until specific dosing guidelines are available, it is strongly recommended that patients receiving chemotherapeutic treatments with such agents refrain from taking [St. John's wort," they conclude.

In a related editorial, Patrick J. Mansky, M.
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Contact: Linda Wang
jncimedia@oupjournals.org
301-841-1287
Journal of the National Cancer Institute
20-Aug-2002