Ventriculolumbar perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosou rea hydrochloride.
We report on the toxicity, intrathecal pharmacokinetics, and therapeutic effect of the ventriculolumbar perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitros our ea hydrochloride (ACNU) against the subarachnoid dissemination of primary central nervous system tumors. Fifteen patients received ventriculolumbar perfusion of ACNU. One was treated with ventriculolumbar perfusion of ACNU alone, and the others underwent concomitant systemic chemotherapy; three of these patients received irradiation as well. ACNU was administered at an initial dose of 0.5 and was increased to 1.5 to 10.0 mg in six patients. Because of a lack of Level 2 or greater toxicity, the subsequent seven patients received 8.7 to 10.0 mg of ACNU dissolved in artificial cerebrospinal fluid (CSF) at a concentration of 0.1 mg/ml, from the start of the treatment. During ACNU administration, the lumbar CSF was drained at approximately the same rate as that of the infusion. Twelve patients received from 3 to 42 courses (average, 14 courses). The cumulative dose of ACNU ranged from 5 to 330.4 mg (average, 82.9 mg). One patient had a convulsion; two patients experienced transient headache, nausea, and vomiting; two others reported transient headache, nausea, vomiting, and fecal incontinence; and one experienced transient nausea, vomiting, and fecal incontinence. No side effects were noted in the other nine patients. When 9.0 to 9.5 mg of ACNU, dissolved in 90 to 95 ml of artificial CSF, was administered for 37 to 52 min, the maximum concentration of ACNU in the lumbar CSF was 9.86 to 12.79 micrograms/ml and the area under the drug concentration-time curve was 260.8 to 502.5 micrograms.min/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
Kochi
M
M
Department of Neurosurgery, Kumamoto University Medical School, Japan.
Kuratsu
J
J
Mihara
Y
Y
Takaki
S
S
Seto
H
H
Uemura
S
S
Ushio
Y
Y
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000401:mortality; D002528:Cerebellar Neoplasms / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000401:mortality; D010478:Chemotherapy, Cancer, Regional Perfusion; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D004305:Dose-Response Relationship, Drug; D004806:Ependymoma / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D006207:Half-Life; D006801:Humans; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D008527:Medulloblastoma / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D008577:Meningeal Neoplasms / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000401:mortality / Q000556:secondary*; D008657:Metabolic Clearance Rate / Q000502:physiology; D009364:Neoplasm Recurrence, Local / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000401:mortality; D017599:Neuroectodermal Tumors / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D015376:Nimustine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000091402:Prohibitins; D013346:Subarachnoid Space; D015996:Survival Rate
C000717331:PHB2 protein, human; D000091402:Prohibitins; D015376:Nimustine