title: The role of pharmacoethnicity in the development of cytotoxic and molecular targeted drugs in oncology.
abstract: The effective and toxic ranges of anticancer drugs are very narrow and, in some cases, inverted. Thus determination of the most appropriate dosage and schedule of administration is crucial for optimal chemotherapy. In common arm trials conducted in Japan and by Southwest Oncology Group (SWOG) that used the same doses and schedules for the administration of carboplatin plus paclitaxel, the frequency of hematological toxicity was significantly higher in the Japanese trials than in the SWOG trial, despite demonstrating similar response rates. The frequency of epidermal growth factor receptor (EGFR) mutations in tumors was significantly higher among East Asian populations, and these populations are also reported to demonstrate a higher response rates to epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs). The prevalence of interstitial lung disease induced by treatment with EGFR-TKIs has been shown to be quite high in the Japanese population. Clinical trials of cetuximab against non-small cell lung cancer and of bevacizumab against stomach cancer have shown that these agents are only active in Caucasians. In a trial examining the use of sorafenib after transarterial chemoembolization in Korean and Japanese patients with advanced hepatocellular carcinoma, the compliance and dose intensity of the drug were quite low compared with other trials. Although not only identified pharmacogenomics differences but also differences in social environment, and regional medical care, including pharmacoeconomics strongly influence ethnic differences in treatment response, further identification and understanding of the pharmacogenomics underlying ethnic differences will be essential to timely and reliable global development of new anticancer drugs.
authors.affiliation: Japanese Society of Medical Oncology, Tokyo, Japan. saijo@jsmo.or.jp
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000208:ethnology; D016461:Chemoembolization, Therapeutic; D002986:Clinical Trials as Topic; D015195:Drug Design; D066246:ErbB Receptors / Q000235:genetics; D005006:Ethnicity; D006801:Humans; D007564:Japan; D017563:Lung Diseases, Interstitial / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy / Q000208:ethnology; D009154:Mutation; D010597:Pharmacogenetics / Q000379:methods*; D056910:Republic of Korea
chemical_list: D066246:ErbB Receptors