A Retrospective Pharmacokinetics and Pharmacogenomics Research of Imatinib in Gastrointestinal Stromal Tumor Treatment

A Retrospective Pharmacokinetics and Pharmacogenomics Research of Imatinib in Gastrointestinal Stromal Tumor Treatment

Gastrointestinal Stromal Tumor

Unknown

Start Date 06/01/2014

Age of Trial (yrs) 10.5

All

KIT/PDGFRA inhibitor

Block KIT

Specifically GIST and only GIST

SYSUCC20141021007

Xueding Wang Sun Yat-sen University

Wei Zhuang, Ph. D 86-13427526343 zhuangw@mail2.sysu.edu.cn Min Huang, Professor +86 020 87331409 ext 101 huangmin@mail.sysu.edu.cn

Oral

This is an observational study and therefore has no phase. Both imatinib sensitive and imatinib non-sensitive patients will be studied.

Brief Summary:
For patients of GIST (Gastrointestinal Stromal Tumor), Imatinib has been widely used in GIST with KIT or PDGFRA sensitive mutations. From clinical points of view, individual differences often occur between different patients, leading diverse effect in ADR and drug effect. Meanwhile, the drug effect and adverse drug reaction was significantly influenced by the pharmacokinetic factors and pharmacodynamic and other factors. In this research, we try to establish a more sensitive method to detect sensitive mutations in plasma and discover the correlation between somatic and germline mutations, plasma trough concentration and drug effect, the association between ADME-associated SNP, Target/Receptor/Pathway-associated SNP, trough concentration and TKI adverse effect. Furthermore, in vivo and in vitro research is also crucial for rational explanation for these clinical phenomenon.

Detailed Description:
The plasma concentration of Imatinib were established. The ADME-associated SNPs included are CYP3A4, CYP3A4, CYP1A1, CYP2C9, CYP2C19, ABCB1, ABCG2, ABCC4, SLC22A1, SLCO1B3 and so on. The Target/Receptor/Pathway-associated SNP s included KIT, PDGFRA, PDGFRB, FLT1, FLT3, MAPK1, SHC1, CCL5, CXCL14 and so on. The somatic mutations included are KIT, PDGFRA, BRAF and so on.