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• W1980606486 abstract "Dear Colleagues: We would like to share with the readers of Journal of Thoracic Oncology an interesting case that we encountered. It serves as a reminder that we should ask our patients about their use of complementary medicines. A 36-year-old woman with no smoking history presented with progressive dyspnea. Computed tomography (CT) of the chest at diagnosis showed a main mass in the right lower lobe with disseminated multiple nodules and multiple interlobular septal thickening in both lungs (Fig. 1A). A needle-aspiration biopsy of the lung nodule was performed, and its histology was consistent with adenocarcinoma. A diagnosis of stage IV adenocarcinoma of lung was made, and she was treated with gefitinib 250 mg per day by mouth as the first-line chemotherapy. Within 9 weeks of gefitinib treatment, she became progressively symptomatic more short of breath. A CT scan of chest revealed progression of her disease (Fig. 1B). She was recommended to discontinue gefitinib because of progressive disease. However, she desired to continue gefitinib therapy. At that time, she informed her physician that she had simultaneously taken multiple complementary herbal medicines including ginseng, Fomes fomentarius, Inonotus obliquus, Phellinus linteus, and selenium along with gefitinib without notification. Thereafter, she discontinued all complementary herbal medicines and took only gefitinib. Her symptoms improved and a follow-up CT scan of chest obtained after 4 weeks revealed a partial response of her disease (Fig. 1C). She continued gefitinib and has been on treatment for 30 weeks with sustained response of her disease (Fig. 1D). The CYP3A4 and CYP3A5 in the intestines and liver play primary role in the first-pass metabolism and systemic clearance of gefitinib.1Li J Karlsson MO Brahmer J et al.CYP3A phenotyping approach to predict systemic exposure to EGFR tyrosine kinase inhibitors.J Natl Cancer Inst. 2006; 98: 1714-1723Crossref PubMed Scopus (89) Google Scholar Therefore, elevated CYP3A4/A5 activity through induction by herbal medicines may result in a decrease in plasma concentrations and in total loss of therapeutic effect of gefitinib. In this case, the patient took multiple mixtures of herbal medicines including ginseng, mushrooms, and selenium. Although ginseng is one of the most widely used herbal medicine, little information is available on drug interactions. Previously a randomized trial had demonstrated that ginseng reduced the anticoagulation effects of warfarin. Because warfarin is eliminated extensively through hepatic CYP enzyme system including CYP1A2, CYP3A4, and CYP2C9, these data suggest that ginseng may induce the CYP enzyme system resulting in lower plasma concentrations of warfarin.2Yuan CS Wei G Dey L et al.Brief communication: American ginseng reduces warfarin's effect in healthy patients: a randomized, controlled trial.Ann Intern Med. 2004; 141: 23-27Crossref PubMed Scopus (196) Google Scholar In addition, an in vitro study showed that ginseng increased CYP3A4 mRNA expression in human hepatocytes.3Raucy JL Regulation of CYP3A4 expression in human hepatocytes by pharmaceuticals and natural products.Drug Metab Dispos. 2003; 31: 533-539Crossref PubMed Scopus (219) Google Scholar These findings suggest that ginseng may increase the clearance of gefitinib through CYP3A4 induction, which result in treatment failure to gefitinib. Besides ginseng, this patient took mushrooms and selenium. Although there are no reports on drug interactions with these complementary medicines, that we are aware of, the possibility of drug-interaction with these medicines and gefitinib should also be taken in consideration. To our knowledge, this is the first report of clinically relevant interaction of gefitinib with complementary herbal medicines. This case demonstrates the possibility of complementary herbal medicines causing treatment failure in a patient who was subsequently responsive to gefitinib. Physicians are encouraged to discuss the use of complementary medicines with their patients and to be aware of possible interaction with gefitinib." @default.
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• W1980606486 date "2008-08-01" @default.
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• W1980606486 title "Drug Interaction Between Complementary Herbal Medicines and Gefitinib" @default.
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