title: Which drug or drug delivery system can change clinical practice for brain tumor therapy?
abstract: The prognosis and treatment outcome for primary brain tumors have remained unchanged despite advances in anticancer drug discovery and development. In clinical trials, the majority of promising experimental agents for brain tumors have had limited impact on survival or time to recurrence. These disappointing results are partially explained by the inadequacy of effective drug delivery to the CNS. The impediments posed by the various specialized physiological barriers and active efflux mechanisms lead to drug failure because of inability to reach the desired target at a sufficient concentration. This perspective reviews the leading strategies that aim to improve drug delivery to brain tumors and their likelihood to change clinical practice. The English literature was searched for defined search items. Strategies that use systemic delivery and those that use local delivery are critically reviewed. In addition, challenges posed for drug delivery by combined treatment with anti-angiogenic therapy are outlined. To impact clinical practice and to achieve more than just a limited local control, new drugs and delivery systems must adhere to basic clinical expectations. These include, in addition to an antitumor effect, a verified favorable adverse effects profile, easy introduction into clinical practice, feasibility of repeated or continuous administration, and compatibility of the drug or delivery system with any tumor size and brain location.
authors.affiliation: Gaffin Center for Neuro-Oncology, Hadassah Hebrew-University Medical Center, Ein Kerem, P.O. Box 12000, Jerusalem 91120, Israel. siegal@hadassah.org.il
authors.forename: Tali
authors.initials: T
authors.lastname: Siegal
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy*; D016503:Drug Delivery Systems; D006801:Humans; D010818:Practice Patterns, Physicians'
chemical_list: D000970:Antineoplastic Agents
keywords: CNS; blood-brain barrier; brain drug delivery; brain tumor; brain tumor therapy; clinical practice; drug development; drug efflux mechanism