制造商： 赛诺菲和Regeneron公司 药理分类： 融合蛋白。 “活性成分”（词）： 谢夫aflibercept 25mg/mL; SOLN稀释后静脉输液，不含防腐剂的。 指示（S）： 结合5 - 氟尿嘧啶，亚叶酸钙，伊立替康（FOLFIRI）治疗转移性结直肠癌（MCRC）抗药性或含奥沙利铂方案已取得进展。 药理作用： ，谢夫-aflibercept是一种重组融合蛋白组成的血管内皮生长因子（VEGF）的胞外结构域的人VEGF受体1和2稠合到人IgG1的Fc部分的结合部分从。谢夫aflibercept充当的可溶性受体，结合到人VEGF-A（平衡解离常数KD VEGF-A165和0.36时，血管内皮生长因子-A121）为0.5时，以人VEGF-B（KD 1.92 PM），和人胎盘生长因子（PLGF-2），KD下午39时。 ZIV-aflibercept通过这些内源性配体的结合，可以抑制其同源受体的结合和激活。这种抑制作用可能会导致减少新生血管，降低血管通透性。 临床试验： 研究是一项随机，双盲，安慰剂对照的研究与转移性结肠癌患者有抗药性或已经在6个月内接受奥沙利铂为基础的联合化疗，有或没有事先贝伐单抗进展。总共有1,226例患者随机（1:1），接受Zaltrap（N = 612; 4mg/kg了1个小时的静脉滴注第1天）或安慰剂（N = 614），联合5 - 氟尿嘧啶加伊立替康[FOLFIRI：伊立替康180mg/m2静脉滴注超过90分钟，亚叶酸钙（DL外消旋体）400mg/m2静脉滴注第1天在同一时间超过2小时，使用Y线，其次是5-FU 400mg/m2静脉推注，其次为2400mg/m2持续静脉输注5-FU超过46小时。治疗周期双臂，每2周重复，直到疾病进展或不可接受的毒性。主要疗效终点是总生存期。治疗任务是分层的ECOG评分（0比1对2），根据之前的治疗与贝伐单抗（是或否）。结果表明，加入Zaltrap FOLFIRI含奥沙利铂方案治疗的患者，显着提高从12.06个月的中位总生存期13.50个月（HR = 0.817，95％CI 0.714-0.935，P = 0.0032），18％相对湿度减少风险。 法律分类： 接收 成人： 开始ZIV aflibercept之前的任何组件的FOLFIRI方案治疗天。给4mg/kg，静脉注射超过1小时，每2周继续下去，直到疾病进展或不可接受的毒性。对于反复发作或严重的高血压，暂停直至控制。复会后，永久地减少2mg/kg灼烧。对于复发性蛋白尿，挂起，直到尿蛋白<2克每24小时，然后永久地减少2mg/kg灼烧。 儿童： 不成立的。 警告/注意事项： 增加出血的危险，监控征兆/症状。严重出血患者无法启动，停止，如果开发。监控停止，如果发生胃肠道穿孔，瘘管形成，受侵害的伤口愈合;。暂停治疗至少4周，择期手术前，不要恢复大手术后至少4周，直到伤口完全愈合。监测BP，每2周和适当治疗高血压发生;暂时中止，直到控制;停止，如果高血压危机/性脑病的发生。停止，如果发生动脉血栓栓塞事件（如短暂性脑缺血发作，脑血管意外，心绞痛）。监测蛋白尿，每24小时内，如果蛋白尿≥2克的暂停，停止，如果出现肾病综合征或血栓性微血管病。监控CBC差在基线和每个周期开始之前，延迟，直到中性粒细胞≥1.5x109 / L。严重腹泻和脱水ESP的风险。中老年（监视器）。停止，如果发生可逆性后部白质脑病综合征。妊娠（部件C）。使用有效避孕和长达3个月，最后一次给药后。哺乳母亲：不推荐使用。 不良反应（S）： 白细胞减少症，腹泻，中性粒细胞减少症，AST / ALT升高，蛋白尿，口腔炎，乏力，血小板减少症，高血压，体重增加，食欲下降，鼻出血，腹痛，发声困难，血肌酐升高，头痛。 如何提供： 单次使用小瓶（100mg/4mL）-1，3 （200mg/8mL）-1 最后更新： 2012年8月30日 IMPORTANT SAFETY INFORMATION FOR ZALTRAP® (ZIV-AFLIBERCEPT) INJECTION FOR INTRAVENOUS INFUSION WARNING: HEMORRHAGE, GASTROINTESTINAL PERFORATION, COMPROMISED WOUND HEALING Severe and sometimes fatal hemorrhage, including gastrointestinal (GI) hemorrhage, has been reported in the patients who have received ZALTRAP in combination with FOLFIRI. Monitor patients for signs and symptoms of GI bleeding and other severe bleeding. Do not administer ZALTRAP in patients with severe hemorrhage. GI perforation including fatal GI perforation can occur in patients receiving ZALTRAP. Discontinue ZALTRAP therapy in patients who experience GI perforation. Severe compromised wound healing can occur in patients receiving ZALTRAP/FOLFIRI. Discontinue ZALTRAP in patients with compromised wound healing. Suspend ZALTRAP for at least 4 weeks prior to elective surgery, and do not resume ZALTRAP for at least 4 weeks following major surgery and until the surgical wound is fully healed. WARNINGS AND PRECAUTIONS Patients treated with ZALTRAP have an increased risk of hemorrhage, including severe and sometimes fatal hemorrhagic events   Monitor patients for signs and symptoms of bleeding. Do not initiate ZALTRAP in patients with severe hemorrhage.   Discontinue ZALTRAP in patients who develop severe hemorrhage.   GI perforation including fatal GI perforation can occur in patients receiving ZALTRAP.   Monitor patients for signs and symptoms of GI perforation.   Discontinue ZALTRAP in patients who experience GI perforation.   Discontinue ZALTRAP in patients with compromised wound healing.   Suspend ZALTRAP for at least 4 weeks prior to elective surgery.   Do not initiate/resume ZALTRAP until at least 4 weeks after surgery and surgical wound is fully healed. Fistula formation involving GI and non-GI sites occurs at a higher incidence in patients treated with ZALTRAP. Discontinue ZALTRAP therapy in patients who develop fistula.   An increased risk of Grade 3-4 hypertension has been observed in patients receiving ZALTRAP.   Monitor blood pressure every two weeks or more frequently and treat with appropriate anti-hypertensive therapy during treatment with ZALTRAP.   Temporarily suspend ZALTRAP until hypertension is controlled, and reduce ZALTRAP dose to 2 mg/kg for subsequent cycles.   Discontinue ZALTRAP in patients with hypertensive crisis.   Arterial thromboembolic events (ATE), including transient ischemic attack, cerebrovascular accident, and angina pectoris, occurred more frequently in patients who have received ZALTRAP. Discontinue ZALTRAP in patients who experience an ATE.   Severe proteinuria, nephrotic syndrome, and thrombotic microangiopathy (TMA) occurred more frequently in patients treated with ZALTRAP.   Suspend ZALTRAP when proteinuria ≥2 grams/24 hours and resume ZALTRAP when proteinuria < 2 grams/24 hours.   If recurrent, suspend until proteinuria < 2 grams/24 hours and then reduce ZALTRAP dose to 2 mg/kg.   Discontinue ZALTRAP if nephrotic syndrome or TMA develops.   A higher incidence of neutropenic complications (febrile neutropenia and neutropenic infection) occurred in patients receiving ZALTRAP.   Delay administration of ZALTRAP/FOLFIRI until neutrophil count is ≥1.5 × 109/L.   Incidence of severe diarrhea and dehydration is increased in patients treated with ZALTRAP⁄FOLFIRI.   The incidence of diarrhea is increased in patients ≥65 years of age. Monitor closely.   Discontinue ZALTRAP in patients who develop reversible posterior leukoencephalopathy syndrome. ADVERSE REACTIONS The most common adverse reactions (all grades, ≥20% incidence) reported at a higher incidence (2% or greater between-arm difference) in the ZALTRAP/FOLFIRI arm, in order of decreasing frequency, were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.   The most common Grade 3-4 adverse reactions (≥5%) reported at a higher incidence (2% or greater between-arm difference) in the ZALTRAP/FOLFIRI arm, in order of decreasing frequency, were neutropenia, diarrhea, hypertension, leukopenia, stomatitis, fatigue, proteinuria, and asthenia.   Infections occurred at a higher frequency in patients receiving ZALTRAP/FOLFIRI (46%, all grades; 12%, Grade 3-4) than in patients receiving placebo/FOLFIRI (33%, all grades; 7%, Grade 3-4), including urinary tract infection, nasopharyngitis, upper respiratory tract infection, pneumonia, catheter site infection, and tooth infection.   In patients with mCRC, venous thromboembolic events (VTE), consisting primarily of deep venous thrombosis and pulmonary embolism, occurred in 9% of patients treated with ZALTRAP/FOLFIRI and 7% of patients treated with placebo/FOLFIRI. Manufacturer: Sanofi and Regeneron Pharmacological Class: Fusion protein. Active Ingredient(s): Ziv-aflibercept 25mg/mL; soln for IV infusion after dilution; preservative-free. Indication(s): 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. Pharmacology: Ziv-aflibercept is a recombinant fusion protein consisting of Vascular Endothelial Growth Factor (VEGF)-binding portions from the extracellular domains of human VEGF Receptors 1 and 2 fused to the Fc portion of the human IgG1. Ziv-aflibercept acts as a soluble receptor that binds to human VEGF-A (equilibrium dissociation constant KD of 0.5 pM for VEGF-A165 and 0.36 pM for VEGF-A121), to human VEGF-B (KD of 1.92 pM), and to human PlGF (KD of 39 pM for PlGF-2). By binding to these endogenous ligands, ziv-aflibercept can inhibit the binding and activation of their cognate receptors. This inhibition can result in decreased neovascularization and decreased vascular permeability. Clinical Trials: Study 1 was a randomized, double-blind, placebo-controlled study in patients with mCRC who are resistant to or have progressed during or within 6 months of receiving oxaliplatin-based combination chemotherapy, with or without prior bevacizumab. A total of 1,226 patients were randomized (1:1) to receive either Zaltrap (N=612; 4mg/kg as a 1 hour IV infusion on day 1) or placebo (N=614), in combination with 5-fluorouracil plus irinotecan [FOLFIRI: irinotecan 180mg/m2 IV infusion over 90 minutes and leucovorin (dl racemic) 400mg/m2 IV infusion over 2 hours at the same time on day 1 using a Y-line, followed by 5-FU 400mg/m2 IV bolus, followed by 5-FU 2400mg/m2 continuous IV infusion over 46 hours]. The treatment cycles on both arms were repeated every 2 weeks until disease progression or unacceptable toxicity. The primary efficacy endpoint was overall survival. Treatment assignment was stratified by the ECOG performance status (0 vs. 1 vs. 2) and according to prior therapy with bevacizumab (yes or no). Results showed that in patients previously treated with an oxaliplatin-containing regimen, adding Zaltrap to FOLFIRI significantly improved median overall survival from 12.06 months to 13.50 months (HR=0.817, 95% CI 0.714– 0.935; p= 0.0032), an 18% relative risk reduction. Legal Classification: Rx Adults: Start ziv-aflibercept prior to any component of the FOLFIRI regimen on treatment day. Give 4mg/kg as an IV infusion over 1 hour 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 <2grams per 24 hours, 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 ≥2grams per 24 hours; 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. Adverse Reaction(s): Leukopenia, diarrhea, neutropenia, proteinuria, AST/ALT increased, stomatitis, fatigue, thrombocytopenia, hypertension, weight increased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, headache. How Supplied: Single-use vials (100mg/4mL)—1, 3 (200mg/8mL)—1