St. John’s Wort Weakens Cancer Drug’s Effect

Tue Aug 20, 2002

By Alison McCook

NEW YORK (Reuters Health) – St. John’s wort, an herbal medicine used to treat depression, may also reduce the effect of a commonly-used chemotherapy drug called irinotecan, according to a study of a small number of patients.

Dr. Alex Sparreboom of the Erasmus MC-Daniel den Hoed Cancer Center in the Netherlands and his colleagues discovered that when five cancer patients received both irinotecan and St. John’s wort, the levels of the active form of irinotecan in the body decreased by 42%, relative to irinotecan given alone.

Furthermore, Sparreboom and his colleagues note, St. John’s wort combined with irinotecan appeared to reduce the cancer drug’s ability to suppress bone marrow cells, a potentially toxic side effect of the treatment that increases patients’ susceptibility to infections.

Although St. John’s wort may help cancer patients combat mild depression and the toxic effects of chemotherapy, the treatment may also impair the ability of irinotecan to adequately rid the body of cancer, the authors note.

“Overall, 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,” Sparreboom and his team write.

According to the report in the August 21st issue of the Journal of the National Cancer Institute, Sparreboom and his colleagues gave irinotecan to five patients with either sarcoma, colorectal cancer, or lung cancer. After a few weeks of treatment, patients began to take 300 milligrams of St. John’s wort three times per day, which they continued for the remainder of the trial.

In an interview with Reuters Health, Sparreboom explained that irinotecan first enters the body as an inactive molecule. The molecule then needs to be turned into a compound known as SN-38 in order to exert its anti-cancer effects.

However, before that activation occurs, liver enzymes can step in and change the chemical properties of irinotecan, and also render it less able to destroy cancer cells. Treatment with St. John’s wort can increase the levels of one of these particular enzymes, known as CYP3A4.

Consequently, other chemotherapy drugs that can be affected by CYP3A4 may also exhibit lower effects in the presence of St. John’s wort, Sparreboom added, such as paclitaxel, docetaxel, and tamoxifen.

In addition, he noted, other substances that either raise or lower levels of CYP3A4 may also affect the ability of chemotherapy drugs to kill cancer cells, substances which include garlic supplements, ginkgo biloba, ginseng, and kava.

“Although not yet studied in relation to chemotherapy drugs, healthcare professionals should ask their patients about the use of herbal products, and should seriously consider the possibility of potentially life-threatening interactions,” Sparreboom said.

In an accompanying editorial, Drs. Patrick J. Mansky and Stephen E. Straus of the National Institutes of Health in Bethesda, Maryland write that surveys show that cancer patients may be more likely than others to turn to alternative therapies. However, the current findings, along with those from other studies, suggest that patients should use complementary and alternative medical (CAM) treatments with caution, the authors note.

“It would be prudent for patients and their oncologists to appreciate that, no matter how beneficial some approaches may appear to be, they are not all safe,” Mansky and Straus write.

“Together, patients and oncologists should consider the options and develop a plan regarding which CAM practices to pursue and which to put aside altogether,” they add.

SOURCE: Journal of the National Cancer Institute 2002;94:1247-1249, 1187-1188.

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