Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood-brain barrier for the treatment of patients with malignant brain tumors.
BACKGROUND
The aim of this study was to determine the safety and efficacy of intraarterial chemotherapy with osmotic opening of the blood-brain barrier (BBB) for the treatment of malignant brain tumors when administered across multiple centers.


METHODS
Patients with primary central nervous system lymphoma (PCNSL), primitive neuroectodermal tumor (PNET), germ cell tumor, cancer metastasis to the brain, or low or high grade glioma were eligible. Prior to entry, magnetic resonance imaging or computed tomography brain scan, medical history, neurologic status, and Karnofsky performance status were reviewed at the coordinating center. Standardized anesthesia and intraarterial catheterization guidelines were followed by a multidisciplinary team at each center. Between March 1994 and November 1997, 5 universities treated 221 adult patients with intraarterial chemotherapy with or without osmotic opening of the BBB (2464 procedures).


RESULTS
Of evaluable patients with PCNSL, 40 of 53 (75%) achieved complete response (CR). All evaluable patients with PNET (n = 17), metastatic disease (n = 12), or germ cell tumor (n = 4) achieved stable disease (SD) or better. Of 57 evaluable patients with glioblastoma multiforme, 45 (79%) achieved SD or better. Asymptomatic subintimal tear occurred in 11 of 221 patients (5%), pulmonary embolism in 6 of 221 (2.7%), and renal toxicity in 4 of 221 (1.8%). One patient with extensive glioma expired within 48 hours after treatment.


CONCLUSIONS
Using standard guidelines and protocols, intraarterial chemotherapy with or without osmotic opening of the BBB is feasible across multiple centers with a low incidence of catheter-related complications. In patients with chemotherapy-sensitive tumors, such as PCNSL, PNET, germ cell tumor, and cancer metastasis to the central nervous system, enhanced delivery results in a high degree of tumor response, with an efficacy profile that is reproducible across multiple centers.
Doolittle
N D
ND
Department of Neurology, Oregon Health Sciences University, Portland, OR 97201-3098, USA.
Miner
M E
ME
Hall
W A
WA
Siegal
T
T
Jerome
E
E
Osztie
E
E
McAllister
L D
LD
Bubalo
J S
JS
Kraemer
D F
DF
Fortin
D
D
Nixon
R
R
Muldoon
L L
LL
Neuwelt
E A
EA
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary; D005240:Feasibility Studies; D005260:Female; D018237:Germinoma / Q000188:drug therapy; D005909:Glioblastoma / Q000188:drug therapy; D005910:Glioma / Q000188:drug therapy; D006801:Humans; D007269:Injections, Intra-Arterial / Q000009:adverse effects / Q000295:instrumentation; D017567:Karnofsky Performance Status; D008223:Lymphoma / Q000188:drug therapy; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017599:Neuroectodermal Tumors / Q000188:drug therapy; D009460:Neurologic Examination; D009995:Osmosis; D012074:Remission Induction; D015203:Reproducibility of Results; D012449:Safety; D014057:Tomography, X-Ray Computed