title: Interstitial chemotherapy for malignant gliomas: the Johns Hopkins experience.
abstract: Malignant gliomas are very difficult neoplasms for clinicians to treat. The reason for this is multifaceted. Many treatments that are effective for systemic cancer are unable to cross the blood-brain barrier and/or have unacceptable systemic toxicities. Consequently, in recent years an effort has been placed on trying to develop innovative local treatments that bypass the blood-brain barrier and allow for direct treatment in the central nervous system (CNS)-interstitial treatment. In this paper, we present our extensive experience in using interstitial chemotherapy as a strategy to treat malignant brain tumors at a single institution (The Johns Hopkins Hospital). We provide a comprehensive summary of our preclinical work on interstitial chemotherapy at the Hunterian Neurosurgery Laboratory, reviewing data on rat, rabbit, and monkey studies. Additionally, we present our clinical experience with randomized placebo-controlled studies for the treatment of malignant gliomas. We compare survival statistics for those patients who received placebo versus Gliadel as initial therapy (11.6 months vs. 13.9 months, respectively) and at the time of tumor recurrence (23 weeks vs. and 31 weeks, respectively). We also discuss the positive impact of local therapy in avoiding the toxicities associated with systemic treatments. Furthermore, we provide an overview of newer chemotherapeutic agents and other strategies used in interstitial treatment. Finally, we offer insight into some of the lessons we have learned from our unique perspective.
authors.affiliation: Department of Neurological Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: H Christopher
authors.initials: HC
authors.lastname: Lawson
authors.forename: Prakash
authors.initials: P
authors.lastname: Sampath
authors.forename: Eileen
authors.initials: E
authors.lastname: Bohan
authors.forename: Michael C
authors.initials: MC
authors.lastname: Park
authors.forename: Namath
authors.initials: N
authors.lastname: Hussain
authors.forename: Alessandro
authors.initials: A
authors.lastname: Olivi
authors.forename: Jon
authors.initials: J
authors.lastname: Weingart
authors.forename: Lawrence
authors.initials: L
authors.lastname: Kleinberg
authors.forename: Henry
authors.initials: H
authors.lastname: Brem
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D002330:Carmustine / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000188:drug therapy*; D003652:Decanoic Acids / Q000627:therapeutic use; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D011091:Polyesters / Q000627:therapeutic use; D011108:Polymers / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003652:Decanoic Acids; D011091:Polyesters; D011108:Polymers; C055401:decanedioic acid-4,4'-(1,3-propanediylbis(oxy))bis(benzoic acid) copolymer; D002330:Carmustine