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Clinical Pharmacology

Herb-Drug Interactions in Oncology: Focus on Mechanisms of Induction

^a Biomedical Analysis, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; ^b Department of Pharmacy & Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands; ^c Department of Medical Oncology & Experimental Therapy, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands

Key Words. Herb–drug interactions • Chemotherapeutics • Induction • PXR • VDR • CAR

Irma Meijerman, Ph.D.,Biomedical Analysis, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University Sorbonnelaan 16, PO Box 80082, 3508 TB Utrecht, The Netherlands. Telephone: 31-30-2537590; Fax: 31-30-2535180; e-mail address: i.meijerman{at}pharm.uu.nl

An increasing number of cancer patients are using complementary and alternative medicines (CAM) in combination with their conventional chemotherapeutic treatment. Considering the narrow therapeutic window of oncolytic drugs, this CAM use increases the risk of clinically relevant herb–anticancer drug interactions. Such a relevant interaction is that of St. John’s wort with the anticancer drugs irinotecan and imatinib. It is, however, estimated that CAM–anticancer drug interactions are responsible for substantially more unexpected toxicities of chemotherapeutic drugs and possible undertreatment seen in cancer patients.

Induction of drug-metabolizing enzymes and ATP-binding cassette drug transporters can be one of the mechanisms behind CAM–anticancer drug interactions. Induction will often lead to therapeutic failure because of lower plasma levels of the anticancer drugs, and will easily go unrecognized in cancer treatment, where therapeutic failure is common.

Recently identified nuclear receptors, such as the pregnane X receptor, the constitutive androstane receptor, and the vitamin D-binding receptor, play an important role in the induction of metabolizing enzymes and drug transporters. This knowledge has already been an aid in the identification of some CAM probably capable of causing interactions with anticancer drugs: kava-kava, vitamin E, quercetin, ginseng, garlic, β-carotene, and echinacea. Evidently, more research is necessary to prevent therapeutic failure and toxicity in cancer patients and to establish guidelines for CAM use.

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