摘要
TAS-102是一种新型口服抗肿瘤复方制剂,由胸腺嘧啶核苷类似物三氟尿嘧啶(trifluridine,FTD)和胸腺嘧啶磷酸化酶抑制剂替吡拉西盐酸盐(tipiracil hydrochloride,TPI)组成。其独特的作用机制在于FTD通过掺入DNA发挥细胞毒作用,而TPI则通过抑制FTD的降解来维持其血药浓度。多项随机、双盲、安慰剂对照的Ⅱ期和Ⅲ期临床试验证实,该药物能显著延长难治性转移性结直肠癌(metastatic colorectal cancer,mCRC)患者的中位总生存期(overall survival,OS)至7.8月,无进展生存期(progression-free survival,PFS)至2.0月,降低62%的死亡风险。本文系统综述了TAS-102的药理学特性,包括其独特的作用机制、药代动力学特征,以及相关的临床前研究和临床研究数据。现有证据表明,TAS-102作为mCRC患者的标准治疗失败后的挽救治疗方案,不仅表现出良好的安全性和耐受性特征,而且在未来联合用药方案中展现出广阔的应用前景。
TAS-102 is a novel oral anticancer combination drug composed of trifluridine(FTD),a thymidine-based nucleoside analog,and tipiracil hydrochloride(TPI),a thymidine phosphorylase inhibitor.In randomized,placebo-controlled phase II and III clinical trials,TAS-102 has demonstrated significant improvements in overall survival(OS)to 7.8 months,progression-free survival(PFS)to 2.0 months in patients with refractory metastatic colorectal cancer(mCRC).This article reviewed the mechanism of action,pharmacokinetics,preclinical data,and clinical evidence of TAS-102 in colorectal cancer.As a salvage treatment option for mCRC patients,TAS-102 exhibits favorable tolerability and holds great potential for future combination therapies.
作者
姚佳林
孙久康
甘芠源
朱陵君
YAO Jialin;SUN Jiukang;GAN Wenyuan;ZHU Lingjun(Oncology Department of the First Affiliated Hospital of Nanjing Medical University,(Jiangsu Provincial People's Hospital),Nanjing 210000,China)
出处
《药物生物技术》
2025年第3期377-381,共5页
Pharmaceutical Biotechnology
基金
国家自然科学基金项目(No.82273407)。
