Clinical pharmacology of EGFR/Met inhibitors in non-small cell lung cancer.
Development of molecular targeting agents, starting with imatinib for chronic myeloid leukemia or gefitinib for non-small cell lung cancer (NSCLC), has recently progressed at a rapid rate. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have already been developed to the 2nd and 3rd generation, and novel drug development targeted towards Met activation, which is an EGFR-TKI resistance mechanism, is ongoing. Although the era of new anticancer agents is moving towards an era of molecular targeting agents, the methods used for drug development are not different than before. In addition to the importance of pharmacokinetics (PK) and pharmacodynamics (PD) for drug development, emerging evidence is also demonstrating the significance of pharmacogenomics, since certain types of gene alteration may greatly affect drug metabolism, excretion, and notably, clinical efficacy. It is desirable to determine optimal doses of anticancer drugs by taking into account these factors that could potentially influence PK/PD. The following article reviews the clinical development of EGFR/Met inhibitors for NSCLC and the clinical pharmacology of these drugs.
Shigehiro
S
Yagishita
Department of Clinical Pharmacology, Group for Translational Research Support Core, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. akhamad@ncc.go.jp.
Akinobu
A
Hamada
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D015195:Drug Design; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met