title: Current status of local therapy in malignant gliomas--a clinical review of three selected approaches.
abstract: 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.
authors.affiliation: Department of Neurosurgery, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany. Tareq.Juratli@uniklinikum-dresden.de
authors.forename: Tareq A
authors.initials: TA
authors.lastname: Juratli
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schackert
authors.forename: Dietmar
authors.initials: D
authors.lastname: Krex
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D002330:Carmustine / Q000008:administration & dosage / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods; D016503:Drug Delivery Systems; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D002330:Carmustine
keywords: AEs; AG; AV; AV-HSV-tk; CB; CEDD; CNS; CSF; CT; CW; Carmustine wafers; Convection-enhanced drug delivery; EGFR; GBM; GCV; HSV; HSV-tk; Herpes simplex virus-thymidine kinase; IL; Local gene therapy; Local therapy; MG; MRI; Malignant gliomas; PE; PFS; Pseudomonas exotoxin; RT; RV; RV-VPC; RV-mediated HSV-tk gene transfer delivered by injections of VPC; Review; TGF-β; TMZ; Transforming growth factor-beta; VPC; adenovirus herpes simplex virus-thymidine kinase; adenoviruses; adverse effects; anaplastic gliomas; carmustine wafers; central nervous system; cerebrospinal fluid; chemotherapy; cintredekin besudotox; convection-enhanced drug delivery; epidermal growth factor receptor; ganciclovir; glioblastoma multiforme; herpes simplex virus; interleukins; magnetic resonance images; malignant gliomas; progression-free survival; radiotherapy; retrovirus RV; temozolomide; virus-producing cells