|
Manufacturer:
Allos Therapeutics
Pharmacological Class:
Antineoplastic (folate analogue inhibitor)
Active Ingredient(s):
Pralatrexate 20mg/mL; soln for IV inj; preservative-free.
Indication(s):
Relapsed or refractory peripheral T-cell lymphoma.
Pharmacology:
Pralatrexate is a folate analogue metabolic inhibitor that competitively inhibits dihydrofolate reductase. It is also a competitive inhibitor of polyglutamylation by the enzyme folylpolyglutamyl synthetase. This inhibition results in the depletion of thymidine and other biological molecules.
Clinical Trials:
This product was approved based on the overall response rate observed in a clinical trial. A clinical benefit, such as improvement in progression-free survival or overall survival, has not been demonstrated.
The safety and efficacy of pralatrexate was examined in an open-label, single-arm, multicenter trial that enrolled 115 patients with relapsed or refractory peripheral T-cell lymphoma. Of these, 111 patients were treated with the study drug (dosed at 30mg/m2 once weekly by IV push over 3–5minutes for 6 weeks in 7-week cycles until disease progression or unacceptable toxicity developed).
The primary efficacy endpoint was overall response rate as assessed by International Workshop Criteria. A secondary endpoint was the duration of response. Duration of response was measured from the first day of documented response to disease progression or death.
In 109 evaluable patients, the response rate (complete response, complete response unconfirmed, and partial response) was 27%. Of the responders, 66% responded within cycle 1. The median time to first response was 45 days, and the median duration of response was 9.4 months in the responders.
Legal Classification:
Rx
Adults:
Prior to administration: mucositis should be ≤Grade 1, platelets should be ≥100,000/µL for first dose and ≥50,000/µL for subsequent doses, absolute neutrophil count should be ≥1000/µL. Give by IV push over 3–5min. 30mg/m2 once weekly for 6 weeks in 7-week cycles; may reduce to 20mg/m2 or interrupt treatment to manage toxicity (see literature for adjustment criteria). Continue until disease progression or unacceptable toxicity develops. Supplement with vitamin B12 (1mg IM every 8–10 weeks, starting within 10weeks before first Folotyn dose) and folic acid (1–1.25mg orally daily, beginning 10 days before starting Folotyn and for 30 days after stopping).
Children:
Not recommended.
Precaution(s):
Adjust dose to manage toxicities (eg, hematological, mucositis, hepatic impairment); see literature. Monitor CBC and for mucositis weekly. Monitor serum chemistry, renal and hepatic function before the 1st and 4th dose per cycle. Renal or hepatic impairment. Pregnancy (Cat.D) (may cause fetal harm), nursing mothers: not recommended.
Interaction(s):
May be potentiated by probenecid, NSAIDs, trimethoprim/sulfamethoxazole, other renally-excreted drugs.
Adverse Reaction(s):
Mucositis, thrombocytopenia, neutropenia, anemia, abnormal liver function tests, nausea, fatigue, pyrexia, dehydration, sepsis, dyspnea.
How Supplied:
Single-use vials (1mL, 2mL)—1
Last Updated:
美国食品药品管理局（FDA）批准美国Allos Therapeutics Inc公司的治疗外周T细胞淋巴瘤（PTCL）药物Folotyn上市。
PTCL为浸润性非霍奇金淋巴瘤，为罕见性疾病。Folotyn被指定为孤儿药，FDA通过快速审批程序批准该药用于治疗复发性或其他化学疗法疗效不佳的PTCL患者。
通过对109名PTCL患者的临床试验研究发现，经成像扫描，27%患者被确定肿瘤体积缩小。通常肿瘤缩小被作为延长癌症患者生存期的替代指标。基于Folotyn能够缩小肿瘤体积，FDA批准其上市。
Folotyn的最常见不良反应为激越或黏膜溃疡，如嘴唇、口腔、消化道溃疡和血小板减少、白细胞减少、发热、恶心及疲惫。
由于Folotyn为有条件批准，Allos公司将继续进行研究，以证明肿瘤缩小与延长患者生存期的正效应。
指示（补）：
复发性或难治性外周T细胞淋巴瘤。
药理作用：
针对pralatrexate是叶酸代谢抑制剂，竞争性抑制二氢叶酸还原酶。这也是polyglutamylation folylpolyglutamyl合成的酶的竞争性抑制剂。在胸苷和其他生物分子枯竭这种抑制作用的结果。
临床试验：
该产品是根据批准的总体反应率在临床试验中观察到。临床好处，如无进展存活率或整体存活率的提高，还没有得到证实。
针对pralatrexate的安全性和有效性进行了检查在一个开放标签，单组，多中心试验，招收复发或难治性外周T细胞淋巴瘤115例。其中，111例患者进行治疗药物的研究（在30mg/m2每周一次通过静脉推6周超过3 - 5分钟，直到疾病进展或不可接受的毒性制定了7个星期的周期剂量）。
主要疗效终点为整体回应率的标准评估国际研讨会。次要终点是响应时间。响应时间是指从记载应对疾病恶化或死亡的第一天。
在评估的109例，缓解率（完全缓解，完全缓解未经证实的，和部分缓解）为27％。的响应者，66％回答在周期1。中位数时间为第一个反应是45天，中位缓解时间为9.4个月的反应。
法律分类：
接收
成人：
在此之前政府当局：粘膜炎应≤1级，血小板首次剂量应为≥10万/μL和≥50,000 /μL的后续剂量，中性粒细胞绝对计数应≥1000/μL。通过静脉给推倒3 - 5分钟。 30mg/m2每周一次为6周，7周周期;可能降低到20mg/m2或中断治疗管理毒性（见调整标准文献）。继续，直到疾病进展或不可接受的毒性发展。与维生素B12（1毫克的IM每8-10个星期，开始之前，首先Folotyn内一零周剂量）和叶酸（1 - 1.25mg每日口服，日前开始启动Folotyn和停药后30天，10天）。
儿童：
不推荐。
预防措施（补）：
调整剂量管理毒性（如血液，粘膜炎，肝功能损害），见文献。央行监测和粘膜炎周。监测血清生化，肾和肝前，每个周期第一和第四剂的作用。肾或肝功能不全。妊娠（Cat.D）（可能导致胎儿的损害），哺乳期妇女：不推荐。
互动（补）：
可能会增强了丙磺舒，NSAIDs类药物，甲氧/磺胺甲基异恶唑，其他renally -排泄的药物。
不良反应（补）：
黏膜炎，血小板减少，白细胞减少，贫血，肝功能异常，恶心，疲劳，发热，脱水，败血症，呼吸困难。
如何提供：
一次性使用瓶（1毫升，液2mL）-1
------------------------------------------------------------
产地国家：美国
所属类别：抗癌药物 ->外周T细胞淋巴瘤
原产地英文药品名：
PRALATREXATE
中文参考药品译名：
普拉曲沙
原产地英文商品名：
FOLOTYN 20mg/ml/vial
中文参考商品译名：
FOLOTYN 20毫克/毫升/瓶
生产厂家英文名：
Allos
生产厂家中文参考译名：
Allos
该药品相关信息网址1：
http://www.folotyn.com/
曾用名：
未知
该药品相关信息网址2：
http://www.drugs.com/folotyn.html | 
