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Importance of dose intensity in neurooncology clinical trials: Summary Report of the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium

Department of Neurology, Oregon Health Sciences University, Portland, OR 97201-3098 (N.D.D., P.G., L.L.M., E.A.N.); Childrens Center for Cancer and Blood Diseases, Childrens Hospital of Los Angeles, Los Angeles, CA 90027 (C.P.A.); Department of Pediatrics, M.D. Anderson Cancer Center, Houston, TX 99030 (W.A.B.); London Regional Cancer Center, London, Ontario, Canada N6A 4L6 (J.G.C.); Neuro-Oncology Program, University of California, Reed Neurological Research Center, Los Angeles, CA 90095-1769 (T.C.); University of Pennsylvania Medical Center, Philadelphia, PA 19104-6160 (S.L.E.); Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455 (W.A.H.); Department of Neurosurgery, Medical University of South Carolina, Charleston, SC 29425-2272 (S.J.P.); Hematology and Medical Oncology, Cleveland Clinic Foundation, Cleveland, OH 44195 (D.P.); Neuro-Oncology Center, Hadassah Hebrew University Hospital, Jerusalem, Israel 91120 (T.S.)

² Address correspondence and reprint requests to Edward A. Neuwelt, Oregon Health Sciences University, Department of Neurology, 3181 S.W. Sam Jackson Park Rd.-L603, Portland, OR 97201-3098.

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 chemo-protectants as part of dose-intensive regimens for chemosensitive brain tumors and development of improved gene therapies for malignant gliomas are discussed.

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