In the first study to examine the combined effects of the cancer chemotherapeutic drug irinotecan and St. John's wort (SJW), a new study provides preliminary evidence that the two agents taken together may reduce the overall effectiveness of the chemotherapy.

SJW is a widely available and popular over-the-counter herbal product used to treat many conditions, including some forms of depression. But it is also known to be a potent stimulator of an enzyme involved in drug metabolism, known as cytochrome P450 (CYP3A4).

"Since about 50% of all drugs are metabolized by CYP3A4, the combination effect we found with St. John's wort and irinotecan might occur with many other anticancer agents," said Dr. Ron Mathijssen of the Rotterdam Cancer Institute in The Netherlands, in a presentation at the annual meeting of the American Association for Cancer Research. "So, the problem is potentially more widespread than this single study shows."

Mathijssen and his colleagues conducted their study after reading scientific papers showing that two ingredients in SJW - hypericin and hyperforin - seemed to have an inducing effect on CYP3A4. Irinotecan is also partly metabolized by CYP3A4.

Three patients were exposed to an initial course of the normal chemotherapeutic regimen of irinotecan, followed three weeks later by a second course that combined irinotecan and SJW. Another group of patients received a combination of irinotecan and SJW, and three weeks later received irinotecan alone to see how long the possible SJW effect might hold.

Complete pharmacological data, available from three patients, revealed that systemic exposure to a measurable metabolite of irinotecan - known as SN-38 - decreased by about 40% with SJW co-treatment. In addition, the researchers found that this effect lasted for more than three weeks after co-treatment.

"This means people have to realize that it's not good enough to stop using St. John's wort just prior to treatment with irinotecan," Mathijssen emphasized. "We do not know at this time, however, how long patients should stop using St. John's wort before being treated with irinotecan as our study was not long enough to make such a determination."

The researchers believe that the results presented for irinotecan may be representative of other anticancer drugs that are partial substrates of CYP3A4.

SOURCE:
93rd Annual Meeting of the American Association for Cancer Research, April 8, 2002, San Francisco, CA