RESUMEN
AstraZeneca KK has participated in 6 international clinical studies in the development of anticancer agents. Having learned from the experiences, we would like to present operational issues of conducting the international studies in the development of anticancer agents from the standpoint of a pharmaceutical company. Also,we would like to show you differences in Japan from Western and other Asian countries, some aspects that we have to improve or make more efforts, and proposals for the future development to provide patients with good products simultaneously worldwide.
Asunto(s)
Antineoplásicos , Ensayos Clínicos como Asunto , Industria Farmacéutica/organización & administración , Agencias Internacionales , Asia , Ensayos Clínicos como Asunto/normas , Ensayos Clínicos como Asunto/tendencias , Industria Farmacéutica/tendencias , Humanos , JapónRESUMEN
AIM: To investigate potential relationships between SNPs and acute interstitial lung disease (ILD) events in Japanese non-small-cell lung cancer patients receiving gefitinib. MATERIALS & METHODS: Japanese non-small-cell lung cancer patients treated with gefitinib from a prospective pharmacoepidemiological cohort with a nested case-control study component ('CCS'; 52 ILD cases, 139 controls) and a retrospective study (28 ILD cases, 55 controls) were genotyped for nearly 500,000 SNPs. Associations between genotype and ILD were evaluated using Fisher's exact test and logistic regression modeling, and false discovery rate analysis was used to adjust for the large number of statistical tests. RESULTS: The CCS data provided some false discovery rate evidence that the significance of top-ranking SNPs exceeded levels expected by chance, suggesting some genuine associations. However, replication analyses using retrospective study data were not supportive and there was little evidence of strong genetic associations from a combined analysis. Adjustment of CCS analyses for clinical variables provided little additional convincing evidence. Significant gene-gene interactions between SNP pairs using CCS data were not confirmed in retrospective study replication analyses. CONCLUSION: Although it is not possible to exclude genetic influences in ILD etiology, common sequence variation is unlikely to explain a major component of ILD risk. Our top results may provide a useful hypothesis-generating starting point for further research.
Asunto(s)
Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inducido químicamente , Enfermedades Pulmonares Intersticiales/genética , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas/efectos adversos , Antineoplásicos/administración & dosificación , Estudios de Casos y Controles , Gefitinib , Estudio de Asociación del Genoma Completo , Humanos , Japón , Polimorfismo de Nucleótido Simple , Quinazolinas/administración & dosificación , Estudios RetrospectivosRESUMEN
Personalized medicine allows the selection of treatments best suited to an individual patient and disease phenotype. To implement personalized medicine, effective tests predictive of response to treatment or susceptibility to adverse events are needed, and to develop a personalized medicine test, both high quality samples and reliable data are required. We review key features of state-of-the-art proteomic profiling and introduce further analytic developments to build a proteomic toolkit for use in personalized medicine approaches. The combination of novel analytical approaches in proteomic data generation, alignment and comparison permit translation of identified biomarkers into practical assays. We further propose an expanded statistical analysis to understand the sources of variability between individuals in terms of both protein expression and clinical variables and utilize this understanding in a predictive test.