Investigational New Drugs

, Volume 32, Issue 4, pp 661–669 | Cite as

Differences in maximum tolerated doses and approval doses of molecularly targeted oncology drug between Japan and Western countries

  • Hideki MaedaEmail author
  • Tatsuo Kurokawa


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.


Anticancer drug Ethnic difference Approval dose Maximum tolerated dose Oncology Japan 



Authors thank to Kentaro Takeda for his statistical advice and Minako Takizawa for her assistance in writing the manuscript.

Funding sources

No specific funding was disclosed.

Conflict of interest disclosures

Hideki Maeda is an employee of Astellas Pharma Inc.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Drug Development and Regulatory Science, Graduate School of Pharmaceutical SciencesKeio UniversityTokyoJapan
  2. 2.Oncology, Clinical Development Department, DevelopmentAstellas Pharma Inc.TokyoJapan

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