Multiple-dose up-titration study to evaluate the pharmacokinetics, safety and antitumor activity of apatinib in advanced gastric adenocarcinoma
文献类型：期刊论文
| 作者 | Wang, Yonggang13; Wang, Chang12; Zhang, Yanqiao11; Hao, Jiqing10; Yang, Nong9; Wang, Jvfeng8; Peng, Min7; Liu, Tianshu6; Zhang, Guifang1; Zhan, Xianbao5 |
| 刊名 | FRONTIERS IN ONCOLOGY
 |
| 出版日期 | 2022-10-18 |
| 卷号 | 12页码:10 |
| 关键词 | apatinib angiogenesis gastric adenocarcinoma pharmacokinetics VEGFR VEGFR-2 |
| ISSN号 | 2234-943X |
| DOI | 10.3389/fonc.2022.876899 |
| 通讯作者 | Gao, Yong(yangyao_6@hotmail.com) ; Yao, Yang(drgaoyong@163.com) |
| 英文摘要 | Background and purposeThe objective of this study was to investigate the pharmacokinetics, safety, and antitumor activity of apatinib, a vascular endothelial growth factor receptor 2 inhibitor, in advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma and evaluate the effect of dose titration on dosage optimization for individual patients. MethodsPatient with advanced gastric adenocarcinoma progressed after at least one line of chemotherapy were enrolled. Apatinib was given orally once daily starting at 500 mg for 14 days, then up-titrated to 750 mg for 14 days, and then proceeded to a maximum dose of 850 mg. Dose up-titration determination was based on toxicity. The 28-day treatment cycles continued until disease progression, intolerable toxicities, withdrawal of consent, or investigator' decision. ResultsA total of 60 patients were enrolled, with 17, 18, and 25 patients receiving a maximum dose of 500 mg, 750 mg, and 850 mg, respectively. The pharmacokinetic parameters varied considerably, with the interpatient coefficient of variation for steady state areas under the plasma concentration time curve (AUC(ss)) and the mean maximum concentration of both > 50%. During 500 mg and 750 mg dosing stage, drug exposures in patients with a maximum dosage of 850 mg were lower than in those not titrated to 850 mg. Patients with total gastrectomy exhibited significantly lower AUC(ss) than patients with partial or no gastrectomy (p = 0.004 and 0.032, respectively). Toxicities were tolerable, and disease control rate was 39.5% (95% CI 25.0%-55.6%). ConclusionsApatinib dose titration based on toxicity could be used in clinical practice to provide optimal dosage for individual patients. |
| WOS关键词 | TYROSINE KINASE ; DOUBLE-BLIND ; PHASE-II ; CHEMOTHERAPY ; CANCER ; MONOTHERAPY ; MULTICENTER ; EXPRESSION ; INHIBITOR ; SURGERY |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000879555200001 |
| 出版者 | FRONTIERS MEDIA SA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/303032]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Gao, Yong; Yao, Yang |
| 作者单位 | 1.Xinxiang Cent Hosp, Dept Oncol, Xinxiang, Peoples R China 2.Tongji Univ, Shanghai East Hosp, Dept Oncol, Sch Med, Shanghai, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 4.Cent South Univ, Dept Oncol, Xiangya Hosp, Changsha, Peoples R China 5.Second Mil Med Univ, Changhai Hosp, Dept Oncol, Shanghai, Peoples R China 6.Fudan Univ, Dept Oncol, Zhongshan Hosp, Shanghai, Peoples R China 7.Wuhan Univ, Dept Oncol, Renmin Hosp, Wuhan, Peoples R China 8.Zhengzhou Univ, Henan Canc Hosp, Dept Internal Med, Affiliated Canc Hosp, Zhengzhou, Peoples R China 9.Hunan Canc Hosp, Affiliated Canc Hosp, Dept Med Oncol, Lung Canc & Gastrointestinal Unit,Xiangya Sch Me, Changsha, Peoples R China 10.Anhui Med Univ, Dept Oncol, Affiliated Hosp 1, Hefei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Yonggang,Wang, Chang,Zhang, Yanqiao,et al. Multiple-dose up-titration study to evaluate the pharmacokinetics, safety and antitumor activity of apatinib in advanced gastric adenocarcinoma[J]. FRONTIERS IN ONCOLOGY,2022,12:10. |
| APA | Wang, Yonggang.,Wang, Chang.,Zhang, Yanqiao.,Hao, Jiqing.,Yang, Nong.,...&Yao, Yang.(2022).Multiple-dose up-titration study to evaluate the pharmacokinetics, safety and antitumor activity of apatinib in advanced gastric adenocarcinoma.FRONTIERS IN ONCOLOGY,12,10. |
| MLA | Wang, Yonggang,et al."Multiple-dose up-titration study to evaluate the pharmacokinetics, safety and antitumor activity of apatinib in advanced gastric adenocarcinoma".FRONTIERS IN ONCOLOGY 12(2022):10. |
入库方式： OAI收割
来源：上海药物研究所
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