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To promote therapeutic development for cancer, it is mandatory to develop new effective drugs in Japan. Oncology phase I trials have been conducted to evaluate the safety, dose-limiting toxicity, and pharmacokinetics of a drug to estimate its maximum tolerated dose. Recommended doses have been determined on the basis of the concept that toxicity can be a surrogate end point for efficacy. Recently, molecular targeted drugs, which specifically inhibit a particular molecular target, have been developed actively and have contributed to improved outcomes of cancer treatment. The efficacy of several molecular targeted drugs is highly dependent on molecular changes in cancer cells, e.g. activating mutations of the EGFR (epidermal growth factor receptor) and ALK (anaplastic lymphoma kinase) translocation.

Japan is now able to participate in multinational clinical studies and aims at obtaining global simultaneous approval. However, we need to keep in mind the factor of ethnic difference between Asians and Caucasians. There is a significant difference between the incidence of EGFR-mutant lung cancer in Asians and non-Asians. It is also important to clarify possible inter-ethnic differences in pharmacokinetics and pharmacodynamics. Since 2003, there have been oncology phase I trials conducted at Shizuoka Cancer Center, including the first-in-human trials. Some recent studies demand evaluation of tumor tissue samples, and we are required to find biomarkers, or surrogate markers of biological response, from early on during development. I will present several phase I trials carried out at Shizuoka Cancer Center.

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