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  • 1
    Electronic Resource
    Electronic Resource
    Neurotoxicity and pharmacokinetics of ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-gluco-pyranoside (MCNU) in dogs (1994)
    Springer
    Journal of neuro-oncology 19 (1994), S. 239-244 
    Details
    ISSN: 1573-7373
    Keywords: meningeal gliomatosis ; methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-gluco-pyranoside ; ventriculolumbar perfusion ; toxicity ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), a water soluble nitrosourea with log P-0.71, may be efficacious in the treatment of subarachnoid dissemination of malignant glioma. We used 2 dogs to study the neurotoxicity and pharmacokinetics of MCNU. MCNU (1 mg), dissolved in 10 ml of artificial CSF, was administered via the right lateral ventricle during a period of 18 to 42 min and the CSF was drained by lumbar puncture. The perfusion was repeated once a week for 10 consecutive weeks. No neurological and systemic symptoms were noted after perfusion. Histological examination of the brain and spinal cord showed local denudation of the ependyma and local subependymal spongy degeneration and gliosis in the lateral ventricle into which MCNU was administered in one dog and local denudation of the ependyma in the other. When administration was over a period of 21 to 38 min, the MCNU concentration in the lumbar CSF peaked at 11.11 to 50.67 Μg/ml, in 28 to 78 min. The area under the drug concentration-time curve (AUC) was 1152 Μg×min/ml on average, significantly larger than that of ACNU. The elimination phase followed linear kinetics and the half-time was 41.1 min on average, significantly longer than that of ACNU. These findings suggest that ventriculolumbar perfusion of MCNU may be effective in the treatment of subarachnoid dissemination of malignant glioma notwithstanding some local histological changes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01053277
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Ventriculolumber perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)- methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride for subarachnoid dissemination of gliomas (1998)
    Springer
    Journal of neuro-oncology 38 (1998), S. 207-212 
    Details
    ISSN: 1573-7373
    Keywords: anaplastic glioma ; glioblastoma ; medulloblastoma ; primitive neuroectodermal tumor ; subarachnoid dissemination ; intrathecal chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The toxicity and therapeutic effect of the ventriculolumber perfussion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl-1-1(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU) against subarachnoid dissemination of gliomas were studied. Twenty-one patients (6 patients with anaplastic glioma, 7 with glioblastoma and 8 with medulloblastoma or PNET) received ventriculolumber perfusion of ACNU when they were diagnosed as having subarachnoid dissemination. The course of perfusion and cumulative dose of ACNU was 10 times and 95 mg on average, respectively. Most of the patients received systemic chemotherapy in combination with perfusion therapy and some patients with radiotherapy. Response rate was 17% and median survival time after the diagnosis of dissemination was 12 months for anaplastic gliomas, 29% and 12 months for glioblastoma, and 88% and over 25 months for medulloblastoma and PNET. The ventriculolumber perfusion of ACNU was performed for prophylactic purpose in 7 patients with high risk at the early postoperative period in combination with conventional adjuvant therapy. The course of perfusion and cumulative dose of ACNU was 2.3 times and 21 mg on average, respectively. One patient developed subarachnoid dissemination and died 22 months after surgery. Other 6 patients survived without dissemination on median over 29 months after surgery. Side effects encountered were headache in 4 patients, nausea and vomiting in 5, a convalsion in 2, right facial weakness in 1, fecal incontinence in 3 and meningitis in 2. They were all temporary except for facial weakness occurred in one patient. These data suggest that the ventriculolumber perfusion of ACNU is a safe and useful in the treatment and prophylaxis against the subarachnoid dissemination of gliomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005973619548
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Randomized Comparison of Intra-arterial Versus Intravenous Infusion of ACNU for Newly Diagnosed Patients with Glioblastoma (2000)
    Springer
    Journal of neuro-oncology 49 (2000), S. 63-70 
    Details
    ISSN: 1573-7373
    Keywords: glioblastoma ; adjuvant therapy ; randomized trial ; ACNU ; intra-arterial administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This prospective randomized trial was performed to compare the effectiveness of intra-arterial ACNU with intravenous ACNU in newly diagnosed patients with supratentorial glioblastoma. The primary end points were overall survival and progression-free survival. Within 3 weeks after surgery, patients were randomly assigned to receive either intravenous or intra-arterial ACNU (80 mg/m2) once every 6 weeks concomitant with radiotherapy. Intra-arterial ACNU was administered for the first 3 courses followed by intravenous administration. Eighty-four patients were enrolled onto this study and among them 82 patients who passed eligibility criteria were analyzed. Patients characteristics were not different significantly between 2 treatment arms. Median survival and progression-free survival time was 59 and 24 weeks, respectively for intra-arterial arm and 56 and 45 weeks, respectively for intravenous arm. There was no significant difference respectively between two treatment arms. Among the prognostic variables including age, Karnofsky performance status, extent of surgery and treatment arm, Cox's proportional hazards model showed that age was the only significant factor for both survival and progression-free survival (P=0.003 and 0.016, respectively). With regard to toxicity, there was no significant difference between two treatment arms. Leukoencephalopathy was not observed in intra-arterial arm. In conclusion, intra-arterial ACNU when administered by the method in this study does not increase the survival and progression-free survival of newly diagnosed patients with glioblastoma over that afforded by intravenous ACNU.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006457502972
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    Paper (German National Licenses)
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