Wang Yonggang, Wang Chang, Zhang Yanqiao, Hao Jiqing, Yang Nong, Wang Jvfeng, Peng Min, Liu Tianshu, Zhang Guifang, Zhan Xianbao, Zeng Shan, Zhang Yifan, Gao Yong, Yao Yang
Department of Oncology, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai, China.
Tumor Center, The First Hospital of Jilin University, Changchun, China.
Front Oncol. 2022 Oct 18;12:876899. doi: 10.3389/fonc.2022.876899. eCollection 2022.
The 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.
Patient 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.
A 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) 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 than patients with partial or no gastrectomy ( = 0.004 and 0.032, respectively). Toxicities were tolerable, and disease control rate was 39.5% (95% CI 25.0%-55.6%).
Apatinib dose titration based on toxicity could be used in clinical practice to provide optimal dosage for individual patients.
https://clinicaltrials.gov/ct2/show/NCT02764268?term=NCT02764268&draw=2&rank=1, NCT02764268.
本研究旨在探讨血管内皮生长因子受体2抑制剂阿帕替尼在晚期胃腺癌或胃食管交界腺癌中的药代动力学、安全性及抗肿瘤活性，并评估剂量滴定对个体患者剂量优化的效果。
纳入至少接受过一线化疗后病情进展的晚期胃腺癌患者。阿帕替尼每日口服一次，起始剂量为500mg，服用14天，然后上调至750mg，服用14天，之后可增至最大剂量850mg。剂量上调的决定基于毒性。28天的治疗周期持续进行，直至疾病进展、出现无法耐受的毒性、患者撤回同意或研究者做出决定。
共纳入60例患者，分别有17例、18例和25例患者接受最大剂量500mg、750mg和850mg的治疗。药代动力学参数差异较大，血浆浓度-时间曲线下稳态面积（AUC）和平均最大浓度的患者间变异系数均>50%。在500mg和750mg给药阶段，最大剂量为850mg的患者的药物暴露低于未滴定至850mg的患者。全胃切除患者的AUC显著低于部分胃切除或未行胃切除的患者（分别为P = 0.004和0.032）。毒性可耐受，疾病控制率为39.5%（95%CI 为25.0%-55.6%）。
基于毒性的阿帕替尼剂量滴定可用于临床实践，为个体患者提供最佳剂量。
https://clinicaltrials.gov/ct2/show/NCT02764268?term=NCT02764268&draw=2&rank=1，NCT02764268 。
