Biodegradable polymer implants to treat brain tumors
Biodegradable polymer implants to treat brain tumors
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DOI：
10.1016/s0168-3659(01)00311-x
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发表时间：
2001-07-06
影响因子：
10.8
通讯作者：
Gabikian, P
中科院分区：
文献类型：
--
作者：
Brem, H;Gabikian, P
我们已经开发了一种系统的方法来发现和评估使用聚合物的脑肿瘤局部治疗策略。我们通过使用标准化疗药物1,3-双（2-氯乙基）-1-亚硝基脲（BCNU）证明了聚合物介导药物递送的可行性，并表明用这种方法局部治疗脑胶质瘤在颅内肿瘤动物模型中是有效的。这导致了针对胶质瘤患者的临床试验，随后Gliadel (TM) [(3.8% BCNU): p(CPP:SA)]被FDA和其他全球监管机构批准。目前正在进行另外22项临床试验，以评估与BCNU聚合物相关的其他问题，例如剂量、与全身治疗的联合以及与各种形式的放射和耐药调节剂的联合。这些试验是使用基于这些模型的脑肿瘤模型进行实验室研究的结果，其他研究小组已经启动了不同药物和新聚合物的新组合的临床试验，用于颅内肿瘤（5-氟尿嘧啶通过聚（D-L丙交酯-共聚物）聚合物传递）和脑外肿瘤（PPE微球中的紫杉醇用于卵巢癌）。由于只有1/3的多型胶质母细胞瘤（GBM）患者对BCNU敏感，因此需要继续寻找其他药物。虽然我们正在攻击主要的耐药机制，但仍然会有肿瘤对BCNU治疗没有反应，但对不同作用机制的药物敏感，如紫杉烷、喜树碱、铂类药物和抗血管生成药物。因此。临床治疗GBM需要探索多种单一药物并最终联合使用最有效的药物。此外，将放射治疗与细胞因子微球递送和抗血管生成药物相结合的多模式方法已显示出令人鼓舞的结果。(C) 2001 Elsevier Science B.V.版权所有
We have developed a systematic approach for the discovery and evaluation of local treatment strategies for brain tumors using polymers. We demonstrated the feasibility of polymer-mediated drug delivery by using the standard chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and showed that local treatment of gliomas by this method is effective in animal models of intracranial tumors. This led to clinical trials for glioma patients, and subsequent approval of Gliadel (TM) [(3.8% BCNU): p(CPP:SA)] by the FDA and other worldwide regulatory agencies. Twenty-two additional clinical trials are currently underway evaluating other issues related to the BCNU polymer, such as dosage, combination with systemic treatments, and combination with various forms of radiation and resistance modifiers. These trials are a result of laboratory investigations using brain tumor models based on these models, other research groups have initiated clinical trials with novel combinations of different drugs and new polymers for both intracranial tumors (5-fluorouracil delivered via poly(D-L lactide-co-glycolide) polymer) and for tumors outside the brain (paclitaxel in PPE microspheres for ovarian cancer). Since only 1/3 of patients with glioblastoma multiforme (GBM) are sensitive to BCNU, the need to search for additional drugs continues. Although we are attacking major resistance mechanisms, there still will be tumors that do not respond to BCNU therapy but are sensitive to agents with different mechanisms of action, such as taxanes, camptothecin, platinum drugs, and antiangiogenic agents. Thus. it is necessary to explore multiple single agents and ultimately to combine the most effective agents for the clinical treatment of GBM, Furthermore, multimodal approaches combining radiotherapy with microsphere delivery of cytokines and antiangiogenic agents have demonstrated encouraging results. (C) 2001 Elsevier Science B.V. All rights reserved.