title: Importance of dose intensity in neuro-oncology clinical trials: summary report of the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium.
abstract: Therapeutic options for the treatment of malignant brain tumors have been limited, in part, because of the presence of the blood-brain barrier. For this reason, the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium, the focus of which was the "Importance of Dose Intensity in Neuro-Oncology Clinical Trials," was convened in April 2000, at Government Camp, Mount Hood, Oregon. This meeting, which was supported by the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, and the National Institute of Deafness and Other Communication Disorders, brought together clinicians and basic scientists from across the U.S. to discuss the role of dose intensity and enhanced chemotherapy delivery in the treatment of malignant brain tumors and to design multicenter clinical trials. Optimizing chemotherapy delivery to the CNS is crucial, particularly in view of recent progress identifying certain brain tumors as chemosensitive. The discovery that specific constellations of genetic alterations can predict which tumors are chemoresponsive, and can therefore more accurately predict prognosis, has important implications for delivery of intensive, effective chemotherapy regimens with acceptable toxicities. This report summarizes the discussions, future directions, and key questions regarding dose-intensive treatment of primary CNS lymphoma, CNS relapse of systemic non-Hodgkin's lymphoma, anaplastic oligodendroglioma, high-grade glioma, and metastatic cancer of the brain. The promising role of cytoenhancers and chemoprotectants as part of dose-intensive regimens for chemosensitive brain tumors and development of improved gene therapies for malignant gliomas are discussed.
authors: Department of Neurology, Oregon Health Sciences University, Portland 97201-3098, USA.
authors: N D
authors: ND
authors: Doolittle
authors: C P
authors: CP
authors: Anderson
authors: W A
authors: WA
authors: Bleyer
authors: J G
authors: JG
authors: Cairncross
authors: T
authors: T
authors: Cloughesy
authors: S L
authors: SL
authors: Eck
authors: P
authors: P
authors: Guastadisegni
authors: W A
authors: WA
authors: Hall
authors: L L
authors: LL
authors: Muldoon
authors: S J
authors: SJ
authors: Patel
authors: D
authors: D
authors: Peereboom
authors: T
authors: T
authors: Siegal
authors: E A
authors: EA
authors: Neuwelt
mesh_terms: D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D016026:Bone Marrow Transplantation; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary / Q000628:therapy; D019328:Buthionine Sulfoximine / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002986:Clinical Trials as Topic / Q000379:methods; D017326:Clinical Trials, Phase III as Topic; D003072:Cognition Disorders / Q000209:etiology; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000493:pharmacokinetics; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D006982:Hypertonic Solutions / Q000494:pharmacology*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000473:pathology; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000503:physiopathology / Q000556:secondary / Q000628:therapy; D015337:Multicenter Studies as Topic / Q000379:methods; D009447:Neuroblastoma / Q000188:drug therapy; D009837:Oligodendroglioma / Q000188:drug therapy; D010539:Permeability / Q000187:drug effects; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D006982:Hypertonic Solutions; D019328:Buthionine Sulfoximine; D005978:Glutathione