title: Intra-arterial ACNU chemotherapy employing 20% mannitol osmotic blood-brain barrier disruption for malignant brain tumors.
abstract: The clinical effects and problems of intra-arterial water-soluble antitumor nitrosourea (ACNU) therapy following osmotic blood-brain barrier modification are discussed. Twenty-one patients with malignant brain tumors were divided into two groups. Group 1 consisted of 16 patients treated by operation, irradiation, and two or more courses of intracarotid infusion of ACNU 100 mg/body (1.7-2.2 mg/kg) following 20% mannitol 200 ml (1.3-1.6 ml/sec) (7 grade 4 astrocytomas, 5 grade 3 astrocytomas, and 4 others). Group 2 consisted of five patients treated by operation, irradiation, and repeated intracarotid infusion of ACNU 100 mg/body alone (grade 4 astrocytoma). The 2-year survival rate in Group 1 was 79% (11 of 14 cases followed up for longer than 2 years) and the 3-year survival rate was 67%. Five of seven grade 4 astrocytoma patients (71%) in Group 1 survived for more than 1 year 6 months, whereas four of five grade 4 astrocytoma in Group 2 died within 1 year 6 months. The measurement of the ACNU concentration in tumor tissues and blood in 11 brain tumors, after intracarotid infusion of ACNU with blood-brain barrier disruption, showed peak values in the tumor tissues of 3.02-32.53 micrograms/gm (mean, 9.67 micrograms/gm), about three to five times as high as that in blood in most cases. This method used in Group 1 appears to be relatively safe without permanent neurological deficits and offers a potential therapeutic effect when used in combination with appropriate premedication in suitable patients.
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo.
authors.forename: M
authors.initials: M
authors.lastname: Miyagami
authors.forename: T
authors.initials: T
authors.lastname: Tsubokawa
authors.forename: M
authors.initials: M
authors.lastname: Tazoe
authors.forename: Y
authors.initials: Y
authors.lastname: Kagawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D002648:Child; D004569:Electroencephalography; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D015376:Nimustine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009997:Osmotic Pressure; D014057:Tomography, X-Ray Computed
chemical_list: D015376:Nimustine; D008353:Mannitol