nd placental growth factor (PlGF), additional angiogenic growth factors that appear to play a role in tumor angiogenesis and inflammation. ZALTRAP has been shown to bind VEGF-A, VEGF-B, and PlGF with higher affinity than their native receptors.
Sanofi Oncology and Regeneron are collaborating on a broad oncology development program, combining the investigational agent ZALTRAP with common chemotherapy regimens in the treatment of patients with advanced cancers. In addition to VELOUR, the program includes one Phase III trial and one Phase II trial, both of which are fully enrolled:
VENICE: First-line treatment for hormone-refractory metastatic prostate cancer in combination with docetaxel and prednisone . An interim analysis is expected to be conducted by an Independent Data Monitoring Committee in mid 2011; final results are anticipated in 2012.
AFFIRM: First-line treatment in metastatic colorectal cancer in combination with 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) . Final results are expected during the second half of 2011.
About Colorectal Cancer
Worldwide, colorectal cancer is the third most commonly diagnosed cancer in males and the second most in females, with more than 1.2 million new cases diagnosed in 2008. Colorectal cancer is one of the deadliest cancers and was responsible for more than 600,000 deaths in 2008 alone. In Europe the overall survival rate is 43 percent, whereas in the United States it is 62 percent; these numbers drop considerably when the cancer spreads to distant organs. The risk of colorectal cancer increases with age – in developed countries, more than 90 percent of cases are diagnosed in individuals older than age 50.
阿柏西普在美获批用于治疗结直肠癌
结直肠癌属危害严重的消化道恶性肿瘤，目前中国结直肠癌发病逐年上升。日前，阿柏西普（Zaltrap，Regeneron/赛诺菲）获FDA批准用于治疗联合传统的FOLFIRI方案（伊立替康、亚叶酸钙、5-氟尿嘧啶）二线治疗已使用含奥沙利铂方案疾病出现进展的转移性结直肠癌患者。相同的适应症等待着欧洲和其他国家的批准。
阿柏西普获批用于治疗结直肠癌是基于一项3期VELOUR（阿柏西普vs安慰剂治疗奥沙利铂方案失败的转移性结直肠癌病人）试验的结果。在1226名病人中，阿柏西普添加到FOLFIRI方案中可显著改善总生存期和无进展生存期。
VELOUR临床试验的首次结果是在2011年的世界胃肠肿瘤大会上公布的。阿柏西普的添加使反应率翻倍，从10%上升到20%。无进展生存期提高了2-3个月，最重要的是，总生存期从12.0个月上升到13.5个月。FDA发布的新闻稿中又增加了临床试验的细节：FOLFIRI方案单独治疗中位无进展生存期为4.7个月，添加阿柏西普上升到了6.9个月。
接受阿柏西普联合FOLFIRI方案的结直肠癌患者中，最常见的不良反应为中性粒细胞减少，腹泻，口腔溃疡，疲劳，高血压，蛋白尿，体重减轻，食欲减退，腹痛，头痛。
阿柏西普是一种血管生成抑制剂，一种重组人融合蛋白，与循环VEGF紧密结合，使其不能与细胞表面受体相互作用。它一直VEGF的A型和B型以及胎盘生长因子，比目前可用的抗血管生成药物如贝伐珠单抗有更广泛的作用机制。
阿柏西普作为Eylea（Regeneron公司联合拜耳公司）被用于眼科疾病，去年被FDA批准治疗新生血管性（湿性）年龄相关性黄斑变性（AMD）。此外，阿柏西普治疗前列腺癌也在研究中，但是Regeneron公司最近声明，在VENICE的3期研究中，对于总生存期没有改善。在这项研究中，阿柏西普添加到多西他赛和泼尼松一线治疗转移性雄激素非依赖性前列腺癌患者。
FDA指出，阿柏西普带有黑框警告，因为具有严重或致命性的出血风险，包括消化道出血，还具有导致消化道穿孔的危险，此外，该药还影响伤口愈合。
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