Herbal Interactions with Anticancer Drugs: Mechanistic and Clinical Considerations

An-Kui      Yang; Shu-Ming      He; Liang      Liu; Jun-Ping      Liu; Ming      Qian Wei; Shu-Feng      Zhou

Abstract

A large number of herbal remedies (e.g. garlic, mistletoe, Essiac, Lingzhi, and astragalus) are used by cancer patients for treating the cancer and/or reducing the toxicities of chemotherapeutic drugs. Some herbal medicines have shown potentially beneficial effects on cancer progression and may ameliorate chemotherapy-induced toxicities. However, there is no or weak scientific basis for the clinical use of these herbal medicines in cancer management and almost none of these plant medicines have been tested in rigorous clinical trials. There are increased reports on the interaction of herbal medicines and anticancer drugs that is becoming a safety concern. For example, a clinical study in cancer patients reported that treatment of St Johns wort at 900 mg/day orally for 18 days decreased the plasma levels of the active metabolite of irinotecan, SN-38, by 42%. In healthy subjects, 2 weeks of treatment with St Johns wort at 900 mg/day significantly decreased the systemic exposure of imatinib by 32%. In women with advanced breast cancer, coadministration of garlic supplement reduced the clearance of docetaxol by 23.1-35.1%, although the difference did not achieve statistical significance. Most anticancer drugs undergo Phase I and/or II metabolism and are substrates of P-glycoprotein, breast cancer resistance protein, multidrug resistance associated proteins, and/or other transporters. Induction and inhibition of these enzymes and transporters are considered as important mechanisms for herb-anticancer drug interactions. Further studies are warranted to investigate potentially harmful herbal interactions with anticancer drugs in patients.

Keywords: Anticancer drug, herbal medicine, herb-drug interaction, toxicity, pharmacokinetics, cytochrome P450, P-glycoprotein, St John's wort, drug resistance