Integrating the anti-VEGF-A humanized monoclonal antibody bevacizumab with chemotherapy in advanced colorectal cancer.
Integrating the anti-VEGF-A humanized monoclonal antibody bevacizumab with chemotherapy in advanced colorectal cancer.
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DOI：
10.3816/ccc.2004.s.010
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发表时间：
2004-10-01
影响因子：
3.4
通讯作者：
Hurwitz, Herbert
中科院分区：
文献类型：
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作者：
Hurwitz, Herbert
最近在治疗结直肠癌(CRC)方面的进展包括纳入新药来治疗一种已知只有一种药物有效的疾病。奥沙利铂和伊立替康已被纳入以5-氟尿嘧啶(5-FU)为基础的方案，在那里它们提高了应答率和存活率。针对表皮生长因子途径和血管内皮生长因子途径的靶向治疗也是肿瘤学研究的前沿，并开始在结直肠癌的治疗中发挥作用。目前的研究正在努力优化靶向治疗与化疗方案的整合，如IFL(伊立替康/团注5-FU/亚叶酸钙[LV])、FOLFIRI(伊立替康/输注5-FU/LV)和FOLFOX(奥沙利铂/输注5-FU/LV)。本文将对单抗贝伐单抗在IFL方案中的掺入进行详细的综述。贝伐单抗靶向血管内皮生长因子-A，这是一种在转移性结直肠癌中普遍表达的重要血管生成信号因子。在IFL方案中加入贝伐单抗显著提高了接受一线治疗的结直肠癌患者的有效率、中位进展时间和总存活率，从而导致食品和药物管理局批准贝伐单抗与基于5-FU的方案结合用于结直肠癌的治疗。贝伐单抗治疗与高血压发病率增加有关。此外，与胃肠道穿孔和心血管事件相关的风险可能略有增加(1%-2%)，但相关增加。在仍在接受贝伐单抗或在接受贝伐单抗治疗后不久接受手术的患者中，观察到伤口愈合并发症的风险略有增加。贝伐单抗联合5-FU也是一种高活性的一线方案。贝伐单抗与其他一线联合疗法的作用，以及它在二线环境中的活性，现在正在进行的临床试验中确定。
Recent advances in the treatment of colorectal cancer (CRC) include the incorporation of new drugs to treat a disease where only one drug was known to be active. Oxaliplatin and irinotecan have been incorporated into 5-fluorouracil (5-FU)-based regimens where they have increased response rates and survival. Targeted therapies against the epidermal growth factor pathway and the vascular endothelial growth factor (VEGF) pathway are also on the forefront of oncology research, and are beginning to play a role in the treatment of CRC. Current research efforts are trying to optimize the integration of targeted therapies into chemotherapy regimens such as IFL (irinotecan/bolus 5-FU/leucovorin [LV]), FOLFIRI (irinotecan/infusional 5-FU/LV), and FOLFOX (oxaliplatin/infusional 5-FU/LV). In this article, the incorporation of the monoclonal antibody bevacizumab into the IFL regimen will be reviewed in detail. Bevacizumab targets VEGF-A, an important angiogenesis signaling factor commonly expressed in metastatic CRC. The addition of bevacizumab to the IFL regimen significantly increased response rates, median time to progression, and overall survival in patients receiving first-line treatment for CRC, thus leading the Food and Drug Administration to approve bevacizumab for the treatment of CRC in combination with 5-FU-based regimens. Bevacizumab treatment is associated with an increased rate of hypertension. In addition, there may be slight (1%-2%) but relevant increased risks related to gastrointestinal perforations and cardiovascular events. A modest increased risk of wound healing complications was observed in patients who underwent surgery while still receiving, or shortly after receiving, bevacizumab. Bevacizumab plus 5-FU is also a highly active first-line regimen. The role of bevacizumab with other first-line combination regimens, as well as its activity in the second-line setting, is now being determined by ongoing clinical trials.