Enhanced chemotherapy delivery by intraarterial infusion and blood-brain barrier disruption in malignant brain tumors: the Sherbrooke experience.
BACKGROUND
The treatment of malignant brain tumors is hampered by the presence of the blood-brain barrier, which limits chemotherapy penetration to the central nervous system (CNS). In recent years, different strategies have been designed to circumvent this physiologic barrier. The osmotic blood-brain barrier disruption (BBBD) procedure is one such strategy, and has been studied extensively in preclinical and clinical studies. The authors detail their experience so far with the procedure in the context of an open Phase II study in the treatment of malignant brain tumors.


METHODS
Patients with histologically proven malignant gliomas, primitive neuroectodermal tumors, primary CNS lymphomas, and metastatic disease to the brain were eligible. Patients enrolled were treated every 4 weeks (1 cycle) for < or = 12 cycles. A methotrexate-based regimen was offered to patients with lymphomas, whereas a carboplatin-based regimen was offered to patients with all other histologies. Before intraarterial chemotherapy infusion, patients were submitted to an osmotic BBBD procedure.


RESULTS
Seventy-two patients were included in the current report. The overall median survival times (MST) from treatment initiation for glioblastoma multiforme (GBM), anaplastic oligodendrogliomas, primary CNS lymphomas, and metastases were, respectively, 9.1, 13.9, not reached, and 9.9 months, whereas time to disease progression was 4.1, 9.2, 12.3, and 3.3 months. The MST from diagnosis was 32.2 months for GBM.


CONCLUSIONS
These encouraging results prompted the authors to further refine their knowledge of the potential contribution of this procedure in the treatment of brain tumors. These authors designed a randomized Phase III study for patients with GBM that is now open.
Fortin
David
D
Department of Neurosurgery and Neuro-oncology, Sherbrooke University, Sherbrooke, Quebec, Canada. david.fortin@USherbrooke.ca
Desjardins
Annick
A
Benko
Andrew
A
Niyonsega
Theophylle
T
Boudrias
Marie
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary; D016190:Carboplatin / Q000627:therapeutic use*; D002648:Child; D018450:Disease Progression; D016503:Drug Delivery Systems; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007261:Infusions, Intra-Arterial; D008223:Lymphoma / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy / Q000473:pathology; D009837:Oligodendroglioma / Q000188:drug therapy / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D016190:Carboplatin; D008727:Methotrexate