2012年8月3日，美国食品药品管理局（FDA）批准ziv-aflibercept（商品名 Zaltrap 美国赛诺菲生产）用于与FOLFIRI（亚叶酸，5- 氟尿嘧啶和伊立替康）联合的化疗方案治疗成人结直肠癌。
Zaltrap 是一种血管生成抑制剂，能阻断肿瘤的血流供应。主要用于癌症已经扩散到身体其他部位（癌症转移）的患者，以及在应用含奥沙利铂方案化疗后出现肿瘤耐药或继续进展的患者。在美国，结直肠癌位于常见癌症榜第四位，也是引起癌症死亡的第四大原因。据国家卫生研究所估计，2012 年将有14万3460名美国人被诊断为结直肠癌，而且51690名患者将死于该病。
“这一批准证明了添加生物制剂（zaltrap）到一个常用的化疗药物方案中（FOLFIRI）的好处”。美国食品药品监督管理局药品评价和研究中心血液学和肿瘤学产品办公室主任Richard Pazdur医学说。“我们已经注意到Zaltrap添加到FOLFIRI方案可改善患者的中位生存时间，并伴随着反应率的改善以及肿瘤进展和生长的延迟。”
在一项针对1226例转移性结直肠癌患者的随机临床研究对Zaltrap的安全性和有效性进行了评估。研究对象为先前接受过以奥沙利铂为基础的联合化疗后出现肿瘤生长的患者；或者手术切除后，奥沙利铂方案跟进的6个月内出现肿瘤再生的患者。参与者接受治疗，直至出现癌症进展或副作用难以耐受。
本研究的目的是评估患者的生存期。在FOLFIRI治疗的基础上增加Zaltrap治疗的患者生存期为13.5 个月，单纯 FOLFIRI方案+安慰剂治疗的患者平均存活期为12个月。20%接受Zaltrap+FOLFIRI 方案治疗的患者肿瘤缩小；而 FOLFIRI+安慰剂组，出现肿瘤缩小的患者比例为11%。
此外，临床试验证也证明了患者的无进展生存期（或称作无癌症进展生存期）也出现改善。Zaltrap+FOLFIRI组无进展生存时间为6.9个月，FOLFIRI+安慰剂组的无进展生存时间为4.7个月。
Zaltrap被批准时同时带有黑框警告，提醒患者和医疗卫生从业人员该药可能会引起的不良反应：严重、甚至致命的出血，包括胃肠道出血和胃肠道穿孔倾向。Zaltrap会导致伤口愈合困难。
在接受Zaltrap+FOLFIRI方案的患者中，观察到的最常见副作用有白细胞减少，腹泻，口腔溃疡，疲劳，高血压，尿蛋白，体重减轻，食欲下降，腹痛以及头痛。
ziv-aflibercept的推荐剂量和时间为:4千克/千克体重，静脉滴注，滴注时间超过1小时，每2周一次，与FOLFIRI治疗方案财时使用。
完整处方信息，请查阅：http://products.sanofi.us/zaltrap/zaltrap.html
Zaltrap(Ziv-Aflibercept Injection for Intravenous Infusion)
ZALTRAP Rx
Generic Name and Formulations:
Ziv-aflibercept 25mg/mL; soln for IV infusion after dilution; preservative-free.
Indications for ZALTRAP:
In combination with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) for patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen.
Adult:
Start ziv-aflibercept prior to any component of the FOLFIRI regimen on treatment day. Give 4mg/kg as an IV infusion over 1hr every 2 weeks; continue until disease progression or unacceptable toxicity. For recurrent or severe hypertension, suspend until controlled. Upon resumption, permanently reduce to 2mg/kg. For recurrent proteinuria, suspend until proteinuria <2g per 24hrs, then permanently reduce to 2mg/kg.
Children:
Not established.
Warnings/Precautions:
Increased risk of hemorrhage; monitor for signs/symptoms. Do not start in patients with severe hemorrhage; discontinue if develops. Monitor for GI perforation, fistula formation, compromised wound healing; discontinue if occurs. Suspend therapy at least 4 weeks prior to elective surgery; do not resume for at least 4 weeks following major surgery and until wound is fully healed. Monitor BP every 2 weeks and treat appropriately if hypertension occurs; temporarily suspend until controlled; discontinue if hypertensive crisis/encephalopathy occurs. Discontinue if arterial thromboembolic events (eg, transient ischemic attack, cerebrovascular accident, angina pectoris) occur. Monitor for proteinuria; suspend if proteinuria ≥2g per 24hrs; discontinue if nephrotic syndrome or thrombotic microangiopathy occurs. Monitor CBC with differential at baseline and prior to start of each cycle; delay until neutrophils ≥1.5x109/L. Risk of severe diarrhea and dehydration esp. in elderly (monitor). Discontinue if reversible posterior leukoencephalopathy syndrome occurs. Pregnancy (Cat. C). Use effective contraception during and up to 3 months after the last dose. Nursing mothers: not recommended.
Pharmacological Class:
Fusion protein.
Adverse Reactions:
Leukopenia, diarrhea, neutropenia, proteinuria, AST/ALT increased, stomatitis, fatigue, thrombocytopenia, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, headache.
Generic Availability:
NO
How Supplied:
Single-use vials (100mg/4mL)—1, 3; (200mg/8mL)—1