title: Differences in maximum tolerated doses and approval doses of molecularly targeted oncology drug between Japan and Western countries.
abstract: Approved doses of a number of drugs in Japan are known to be different from those in the United States (US) and the European Union (EU), and doses are often set lower for the Japanese than for the western people. Similarly, some oncology drugs also have lower dose approved for the Japanese than for the western people. A total of 40 oncology drugs were approved as new molecular entities in Japan between 2001 and 2013. Of the 40 drugs, 21 were molecularly targeted drugs and 13 were cytotoxic drugs. Five (12.5 %) of the 40 drugs had different approved dose from that in the US and the EU. Of the 13 cytotoxic drugs, four drugs (30.8 %) differed in approved dose, while all the molecularly targeted drugs (21 of 21 drugs) had the same approved dose. We compared the maximum tolerated dose (MTD) of the 21 molecularly targeted drugs in the Japanese with that in the western people and found that the MTD was determined lower in the Japanese than that in the western people (two drugs), was not different (10 drugs), and MTD was not determined in the Japanese and incommensurable because of the different dose range tested in Japan (nine drugs). All the molecularly targeted drugs are the same in approved doses and few molecularly targeted drugs differ in MTD between Japan and the Western countries.
authors.affiliation: Drug Development and Regulatory Science, Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan, hideki.maeda@z7.keio.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Maeda
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kurokawa
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D017277:Drug Approval / Q000379:methods; D005062:European Union; D006801:Humans; D007564:Japan; D020714:Maximum Tolerated Dose; D009369:Neoplasms / Q000188:drug therapy*; D014481:United States
chemical_list: D000970:Antineoplastic Agents