简介：

FDA正式批准了阿糖胞苷注射剂(cytarabine liposome injection，DepoCyt)，用于治疗一种致命性的淋巴瘤综合征——肿瘤性脑膜炎。此前，DepoCyt获得了FDA的快速批准资格。
FDA批准本品基于2项随机临床研究的结果。在研究中，受试者为200例新生肿瘤性脑膜炎患者，肿瘤类型有实体瘤、淋巴瘤和血液瘤等。第1项研究表明，大多数接受本品治疗的患者无疾病的神经性恶化。第2项研究表明，通过测定脑脊液(CSF)中恶性细胞清除率，接受本品治疗的患者的全细胞响应有所增强。
阿糖胞苷可以控制肿瘤性脑膜炎，但该药半衰期短，需每周进行2次脊柱注射。DepoCyt为化疗试剂阿糖胞苷的持续释放剂型，每2周给药1次。本品可逐渐释放至脑脊液中，因此具有较长的半衰期、延长的治疗浓度及更均匀的药物分布。
DepoCyt是一种缓释的化学治疗药物。阿糖胞苷可以控制淋巴瘤性脑膜炎，但是由于其半衰期较短，每周需要进行2次脊椎穿刺，而DepoCyt仅需2周使用1次。DepoCyt可以将阿糖胞苷缓慢的释放进入脑脊髓液，因此可以显著的增加其半衰期，延长作用时间，而且其分布也更加均匀。只有进行过膜内肿瘤化学治疗药物操作的有资格的医师才可以使用DepoCyt。在所有的临床试验中最常见的不良反应为化学性蛛网膜炎，该不良反应的最初症状为恶心、呕吐、头痛已经发烧。如果不采取治疗措施，化学性蛛网膜炎有致命的危险。同时服用地塞米松可以减少该不良反应的发生率和严重程度。因此使用DepoCyt治疗的患者应同时使用地塞米松，以缓和化学性蛛网膜炎的症状。

DEPOCYT is a sustained release formulation of cytarabine approved for the treatment of lymphomatous meningitis.
The unique liposomal encapsulation of DEPOCYT is designed to release cytarabine into the cerebrospinal fluid over an extended period of time: DEPOCYT has a half-life of up to 82.4 hours, compared to 3.4 hours for unencapsulated cytarabine.As a result, treatment with DEPOCYT is well distributed throughout the CSF and offers prolonged exposure of the tumor cells to cytarabine.Because DEPOCYT is a sustained release formulation, it provides convenient dosing of every two weeks as compared to twice weekly with unencapsulated cytarabine.
Two randomized, multi-center clinical trials of DEPOCYT in patients with neoplastic meningitis (n=223) were conducted; 57 patients had
lymphomatous meningitis. 
Patients were treated intrathecally with either with 50mg of DEPOCYT every two weeks orunencapsulatedcytarabine twice weekly. 
In Study  DEPOCYT achieved a complete response rate of 41% compared with only 6% for unencapsulated cytarabine.  In Study 2 lymphomatous meningitis subset analysis, DEPOCYT achieved a complete response rate of 33% compared with 17% for unencapsulated cytarabine. 
Complete response was prospectively defined as both (i) conversion of positive to negative CSF cytology and (ii) the absence of neurologic progression.
In the controlled clinical trials, the most common severe adverse event was chemical arachnoiditis. Other reported adverse events included headache, nausea, and vomiting; these adverse events are manageable and are consistent with those commonly seen with intrathecal chemotherapy.
Dexamethasone should be concomitantly administered with DEPOCYT(cytarabine liposome injection) to reduce the risk and severity of chemical arachnoiditis.
Cytarabine, the active component of DEPOCYT, can cause fetal harm if a pregnant woman is exposed to the drug systemically. However, the concern for fetal harm following intrathecal DEPOCYT administration is low because systemic exposure to cytarabine is negligible.
Despite the low apparent risk for fetal harm, women of childbearing potential should be advised to avoid becoming pregnant.
DEPOCYT is contraindicated in patients who are hypersensitive to cytarabine or any component of the formulation, and in patients with active meningeal infection.

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附件:
200971300280710.pdf