a Department of Medical Oncology , Vall D'Hebron University Hospital Barcelona/Universitat Autònoma de Barcelona , Barcelona , Spain.
b Department of Medical Oncology , Institut Català d'Oncologia-IDIBELL, Universitat de Barcelona , Barcelona , Spain.
Expert Opin Pharmacother. 2018 Apr;19(6):623-629. doi: 10.1080/14656566.2018.1453497. Epub 2018 Mar 28.
Despite major progress in treating advanced colorectal cancer (CRC), prognosis in this population after progression on standard treatment remains dismal and the development of new drugs represents an unmet need. Historically, fluoropyrimidines have played a major role in the treatment of metastatic CRC. TAS-102, a novel combination of trifluridine and tipiracil hydrochloride, has demonstrated improvement in overall survival in the refractory CRC setting, with a safe toxicity profile. Areas covered: A literature review of published clinical studies was performed. Herein, the authors review the pharmacological and clinical data of TAS-102 when used in metastatic CRC, both as a single agent as well as in novel combinations under investigation. Expert opinion: The addition of TAS-102 to the therapeutic armamentarium of metastatic CRC is an encouraging breakthrough considering the demonstrated survival benefit and favorable tolerability profile. Combinations with other agents are under clinical investigation in different settings in an attempt to widen its use. To optimize treatment in today's era of molecular oncology, efforts should be focused on understanding primary and secondary resistance mechanisms, along with the identification of potential biomarkers of response.
尽管在治疗晚期结直肠癌(CRC)方面取得了重大进展,但在标准治疗进展后,该人群的预后仍然不佳,因此需要开发新的药物。氟嘧啶类药物在转移性 CRC 的治疗中一直发挥着重要作用。替拉扎尼(TAS-102)是一种由三氟尿嘧啶和盐酸替匹嘧啶组成的新型药物组合,在难治性 CRC 环境中显示出总生存期的改善,且具有安全的毒性特征。
对已发表的临床研究进行了文献复习。在此,作者综述了替拉扎尼在转移性 CRC 中的药理学和临床数据,包括单药治疗以及正在研究的新型联合治疗。
考虑到替拉扎尼在生存获益和良好的耐受性方面的表现,将其添加到转移性 CRC 的治疗方法中是一个令人鼓舞的突破。正在不同环境下进行与其他药物联合应用的临床试验,以扩大其应用范围。为了在当今的分子肿瘤学时代优化治疗,应努力了解原发性和继发性耐药机制,并确定潜在的反应生物标志物。