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[抗血管生成治疗与结直肠癌]

[Anti-angiogenic treatment and colorectal cancer].

作者信息

André Thierry, Tournigand Christophe, Abbas Fadi, Louvet Christophe, de Gramont Aimery

机构信息

Service d'oncologie médicale, hôpital Tenon, 4, rue de la Chine, 75970 Paris Cedex 20.

出版信息

Bull Cancer. 2007 Jul;94 Spec No:S211-9.

Abstract

For many years, oncology research has focused on the study of therapeutic agents able to target a different cell than a cancer cell. Tumor angiogenesis mediated by the vascular endothelial growth factor (VEGF) was one of the pathways investigated. The treatment of metastastic colorectal cancer has dramatically evolved. Overall survival has significantly improved, owing to the use in standard daily practice of irinotecan and oxaliplatin, combined with 5-fluorouracil (5FU) and leucovorin. This review summarizes efficacy and safety data of two antiangiogenic agents, bevacizumab (a monoclonal antibody inhibiting VEGF) and vatalanib (a tyrosine kinase inhibitor of VEGF), assessed in phase III trials in metastastic colorectal cancer. The efficacy of bevacizumab combined with 5FU-leucovorin +/- irinotecan based on overall survival data which was demonstrated in the first-line treatment of metastastic colorectal cancer in studies conducted in the US, has recently been demonstrated in the same indication based on progression survival when combined to oxaliplatin and a fluoropyrimidine (capecitabine or 5FU-leucovorin). Bevacizumab combined to infusion chemotherapy with 5FU-leucovorin with or without irinotecan is indicated, in Europe, in the first-line treatment of metastastic colorectal cancer. While in the US, prescription options are wider in the first-line treatment, it is combined to chemotherapies with a fluoropyrimidine +/- irinotecan or oxaliplatin, and in second line as well with fluoropyrimidine and oxaliplatin. Several questions regarding the optimal use of bevacizumab still remain to be answered in the treatment of metastastic colorectal cancer. Vatalanib has not shown benefit in this pathology.

摘要

多年来,肿瘤学研究一直专注于能够靶向不同于癌细胞的细胞的治疗药物的研究。血管内皮生长因子(VEGF)介导的肿瘤血管生成是其中一条被研究的途径。转移性结直肠癌的治疗有了显著进展。由于在日常标准治疗中使用伊立替康和奥沙利铂,并联合5-氟尿嘧啶(5FU)和亚叶酸,总生存期有了显著改善。本综述总结了两种抗血管生成药物贝伐单抗(一种抑制VEGF的单克隆抗体)和伐他拉尼(一种VEGF酪氨酸激酶抑制剂)在转移性结直肠癌III期试验中评估的疗效和安全性数据。基于在美国进行的研究中转移性结直肠癌一线治疗中总生存期数据所证实的,贝伐单抗联合5FU-亚叶酸+/-伊立替康的疗效,最近在与奥沙利铂和氟嘧啶(卡培他滨或5FU-亚叶酸)联合时基于无进展生存期在相同适应症中得到了证实。在欧洲,贝伐单抗联合5FU-亚叶酸静脉化疗(有或无伊立替康)被用于转移性结直肠癌的一线治疗。而在美国,一线治疗的处方选择更广泛,它与氟嘧啶+/-伊立替康或奥沙利铂联合化疗,在二线治疗中也与氟嘧啶和奥沙利铂联合使用。在转移性结直肠癌的治疗中,关于贝伐单抗最佳使用的几个问题仍有待解答。伐他拉尼在这种疾病中未显示出益处。

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