Department of Neurosurgery, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany.
Pharmacol Ther. 2013 Sep;139(3):341-58. doi: 10.1016/j.pharmthera.2013.05.003. Epub 2013 May 18.
Malignant gliomas are the most frequently occurring, devastating primary brain tumors, and are coupled with a poor survival rate. Despite the fact that complete neurosurgical resection of these tumors is impossible in consideration of their infiltrating nature, surgical resection followed by adjuvant therapeutics, including radiation therapy and chemotherapy, is still the current standard therapy. Systemic chemotherapy is restricted by the blood-brain barrier, while methods of local delivery, such as with drug-impregnated wafers, convection-enhanced drug delivery, or direct perilesional injections, present attractive ways to circumvent these barriers. These methods are promising ways for direct delivery of either standard chemotherapeutic or new anti-cancer agents. Several clinical trials showed controversial results relating to the influence of a local delivery of chemotherapy on the survival of patients with both recurrent and newly diagnosed malignant gliomas. Our article will review the development of the drug-impregnated release, as well as convection-enhanced delivery and the direct injection into brain tissue, which has been used predominantly in gene-therapy trials. Further, it will focus on the use of convection-enhanced delivery in the treatment of patients with malignant gliomas, placing special emphasis on potential shortcomings in past clinical trials. Although there is a strong need for new or additional therapeutic strategies in the treatment of malignant gliomas, and although local delivery of chemotherapy in those tumors might be a powerful tool, local therapy is used only sporadically nowadays. Thus, we have to learn from our mistakes in the past and we strongly encourage future developments in this field.
恶性胶质瘤是最常见、最具破坏性的原发性脑肿瘤，患者生存率低。尽管考虑到这些肿瘤的浸润性，完全通过神经外科手术切除这些肿瘤是不可能的，但手术切除后辅以辅助治疗，包括放射治疗和化学疗法，仍然是目前的标准治疗方法。全身化疗受到血脑屏障的限制，而局部给药方法，如药物浸渍晶片、对流增强药物输送或直接瘤周注射，则提供了绕过这些屏障的有吸引力的方法。这些方法是直接递送电化疗或新型抗癌药物的有前途的方法。几项临床试验表明，局部化疗对复发性和新诊断的恶性胶质瘤患者的生存影响存在争议。我们的文章将回顾药物浸渍释放的发展，以及对流增强输送和直接注射到脑组织中，这些方法主要用于基因治疗试验。此外，它将重点介绍对流增强输送在治疗恶性胶质瘤患者中的应用，特别强调过去临床试验中的潜在缺陷。尽管恶性胶质瘤的治疗需要新的或额外的治疗策略，并且尽管局部化疗可能是这些肿瘤的有力工具，但目前局部治疗的应用仍很零星。因此，我们必须从过去的错误中吸取教训，并强烈鼓励该领域的未来发展。
