课件：一线mCRC患者靶向药物治疗的困惑与思考焦智民.pptVIP

THANK YOU SUCCESS * * 可编辑 Until 1996, 5-fluorouracil (5-FU) modulated by leucovorin (LV) was the only therapy available for the treatment of MCRC. Since then, 伊立替康, capecitabine, 奥沙利铂 , and most recently, the biologic agents 西妥昔单抗, 贝伐单抗 and, 帕尼单抗, have become available, adding to the armamentarium of therapies for MCRC. 5-FU is a fluoropyrimidine, which upon conversion to its active metabolite (fluorodeoxyuridine monophosphate [FdUMP]) inhibits thymidylate synthase preventing pyrimidine and therefore DNA synthesis. 5-FU has been a mainstay of anticancer therapy since it was introduced in 1960. The addition of the biomodulator LV improves response rates (RRs) seen with 5-FU therapy. 伊立替康, a topoisomerase I inhibitor, was approved initially as a second-line treatment for patients with MCRC in 1996. In 2002, capecitabine, an oral fluoropyrimidine prodrug converted into 5-FU by thymidine phosphorylase, was the first oral agent approved for the treatment of MCRC. Capecitabine had been approved previously for the treatment of metastatic breast cancer in 1998. 奥沙利铂 , a third-generation platinum analog that induces DNA crosslinks and results in apoptosis, was initially approved for use in the United States in 2001 and is currently approved in both the first- and second-line settings. 西妥昔单抗, a chimeric antibody to the epidermal growth factor receptor (EGFR), was approved recently for the treatment of second-line MCRC in patients who overexpress EGFR. 贝伐单抗, a humanized monoclonal antibody to the vascular endothelial growth factor (VEGF)—a key regulator of tumor angiogenesis—was approved in February 2004 for the treatment of first-line MCRC. 帕尼单抗, a recombinant human monoclonal antibody that binds to EGFR, was approved in September 2006 for the second-line treatment of EGFR-expressing MCRC. In addition to new therapies, new therapeutic concepts also have been developed in the past 20 years, including the use of both adjuvant and neoadjuvant chemotherapy (CT). 吉非替尼、厄洛替尼