title: The Dissociation of Gefitinib Trough Concentration and Clinical Outcome in NSCLC Patients with EGFR Sensitive Mutations.
abstract: Gefitinib is an essential drug for NSCLC patients harboring EGFR sensitive mutations. The approved dose 250 mg/day is based on limited clinical trials, this research aims to explore the relationship between drug exposure and gefitinib response. C trough of 87 NSCLC patients harboring EGFR sensitive mutations were determined by LC-MS/MS. The median of C trough was 173.9 ng/ml (P25-P75, 130.5-231.2 ng/ml), and cutoff value 200 ng/ml was determined by X-Tile. The PFS between C trough < 200 ng/ml and C trough ≥ 200 ng/ml groups were not significantly different (17.3 VS 14.8 months; p = 0.258). C trough was not significantly associated with rash, diarrhea and hepatotoxicity. Non-smokers enjoyed longer PFS than smokers (18.7 VS 9.3 months; p = 0.025). The results showed that, for NSCLC patients with EGFR sensitive mutations, the PFS in lower trough concentration group were not inferior to that in higher trough concentration group and dose reduction is a rational suggestion for adjustment of dose regimen for aforementioned patients. More clinical trials are warranted to explore the precision dose schedule of gefitinib.
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Xin
authors.affiliation: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Xueding
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Clinical Trial Center, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China.
authors.forename: Zhihuang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D002853:Chromatography, Liquid; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use*; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib