Polymeric drug delivery for the treatment of glioblastoma
Polymeric drug delivery for the treatment of glioblastoma
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DOI：
10.1093/neuonc/nou360
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发表时间：
2015-03-01
期刊：
影响因子：
15.9
通讯作者：
Asher, Anthony L.
中科院分区：
文献类型：
--
作者：
Wait, Scott D.;Prabhu, Roshan S.;Asher, Anthony L.
胶质母细胞瘤（GBM）仍然是一个几乎普遍致命的诊断。目前的治疗主要包括最大安全手术切除术，然后进行放射治疗（RT），伴随替莫唑胺（TMZ），然后每月TMZ（“Stupp方案”）。几种化疗药物已被证明在高级别胶质瘤（HGG）的治疗中具有适度的疗效，但血脑屏障的不渗透性仍然是一个主要的传递障碍。聚合物药物递送系统被开发用于允许生物活性物质在各种条件下的受控局部释放，可以实现活性剂的高局部浓度，同时限制全身毒性。将聚合物递送的卡莫司汀（BCNU）晶片放置在肿瘤切除腔的表面上，可以在手术和放化疗之间的标准延迟期间为残留的肿瘤细胞提供立即化疗。在2项III期研究中，研究了BCNU晶片植入作为新诊断的HGG的单药化疗（与RT），报告了中位总生存期的显着增加。许多研究调查了联合化疗与BCNU片在新诊断或复发性HGG中的杀瘤协同作用，主要研究重点是将BCNU片整合到标准Stupp方案的多模式治疗中。总体而言，这些研究的结果在安全性和有效性方面令人鼓舞。然而，数据必须根据所进行研究的性质加以限定。目前，还没有BCNU晶片与标准Stupp方案的III期研究。我们回顾了这一模式的基本原理、生物化学、药代动力学和研究历史（包括毒性特征）。
Glioblastoma (GBM) remains an almost universally fatal diagnosis. The current therapeutic mainstay consists of maximal safe surgical resection followed by radiation therapy (RT) with concomitant temozolomide (TMZ), followed by monthly TMZ (the "Stupp regimen"). Several chemotherapeutic agents have been shown to have modest efficacy in the treatment of high-grade glioma (HGG), but blood-brain barrier impermeability remains a major delivery obstacle. Polymeric drug-delivery systems, developed to allow controlled local release of biologically active substances for a variety of conditions, can achieve high local concentrations of active agents while limiting systemic toxicities. Polymerically delivered carmustine (BCNU) wafers, placed on the surface of the tumor-resection cavity, can potentially provide immediate chemotherapy to residual tumor cells during the standard delay between surgery and chemoradiotherapy. BCNU wafer implantation as monochemotherapy (with RT) in newly diagnosed HGG has been investigated in 2 phase III studies that reported significant increases in median overall survival. A number of studies have investigated the tumoricidal synergies of combination chemotherapy with BCNU wafers in newly diagnosed or recurrent HGG, and a primary research focus has been the integration of BCNU wafers into multimodality therapy with the standard Stupp regimen. Overall, the results of these studies have been encouraging in terms of safety and efficacy. However, the data must be qualified by the nature of the studies conducted. Currently, there are no phase III studies of BCNU wafers with the standard Stupp regimen. We review the rationale, biochemistry, pharmacokinetics, and research history (including toxicity profile) of this modality.