Yang Hang, Wang Yu, Zhan Jing, Xia Yi, Sun Peng, Bi Xi-Wen, Liu Pan-Pan, Li Zhi-Ming, Li Su, Zou Ben-Yan, Jiang Wen-Qi
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Oncotarget. 2015 Dec 22;6(41):44049-56. doi: 10.18632/oncotarget.5833.
To determine the safety of Puquitinib Mesylate (XC-302), an oral inhibitor of phosphatidylinositol 3-kinase, in treating relapsed or refractory non-Hodgkin's lymphoma (NHL).
Between October 2013 and July 2015, 21 patients from Sun Yat-sen University Cancer Center were treated twice daily on each day of a 28-day cycle (median number of cycles, 2; maximum, 20) with XC-302 at a post prandial dose of 25 mg, 37.5 mg, or 50 mg. Adverse events (AEs), AUClast and Cmax, response rates, and overall survival were assessed.
Patients had received a median (range) of 1 (1 to 3) previous cancer treatments. At the latest follow-up, two patients were still benefitting from the study. The most common drug-related AEs were elevations in alanine transaminase (ALT, 14 of 21 patients) and aspartate transaminase (AST, 7 of 21 patients). Four patients, both in the-50-mg group, had dose-limiting toxicities, and therapy was discontinued in a fifth because of persistent abnormal liver function. The overall response rate was 2 of19. Serum concentrations of XC-302 increased in a dose-dependent pattern. Median progression-free survival in all patients was 1.9 (95% CI, 1.7 to 2.0) months.
XC-302 has an acceptable safety profile and offers potential therapeutic value to patients with relapsed or refractory non-Hodgkin lymphoma.
确定磷脂酰肌醇3激酶口服抑制剂甲磺酸普喹替尼（XC-302）治疗复发或难治性非霍奇金淋巴瘤（NHL）的安全性。
2013年10月至2015年7月期间，中山大学肿瘤防治中心的21例患者在28天周期的每一天接受两次治疗（中位周期数为2；最大为20），餐后服用剂量为25mg、37.5mg或50mg的XC-302。评估不良事件（AE）、末次观察浓度（AUClast）和峰浓度（Cmax）、缓解率和总生存期。
患者既往接受癌症治疗的中位次数（范围）为1次（1至3次）。在最近一次随访时，两名患者仍从研究中获益。最常见的药物相关不良事件是丙氨酸转氨酶升高（21例患者中有14例）和天冬氨酸转氨酶升高（21例患者中有7例）。50mg组的4例患者出现剂量限制性毒性，另有1例因肝功能持续异常而停药。19例患者的总缓解率为2例。XC-302的血清浓度呈剂量依赖性增加。所有患者的中位无进展生存期为1.9个月（95%CI，1.7至2.0）。
XC-302具有可接受的安全性，对复发或难治性非霍奇金淋巴瘤患者具有潜在的治疗价值。
