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1. Kieran MW, Packer RJ, Onar A, Blaney SM, Phillips P, Pollack IF, Geyer JR, Gururangan S, Banerjee A, Goldman S, Turner CD, Belasco JB, Broniscer A, Zhu Y, Frank E, Kirschmeier P, Statkevich P, Yver A, Boyett JM, Kun LE: Phase I and pharmacokinetic study of the oral farnesyltransferase inhibitor lonafarnib administered twice daily to pediatric patients with advanced central nervous system tumors using a modified continuous reassessment method: a Pediatric Brain Tumor Consortium Study. J Clin Oncol; 2007 Jul 20;25(21):3137-43
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  • [Title] Phase I and pharmacokinetic study of the oral farnesyltransferase inhibitor lonafarnib administered twice daily to pediatric patients with advanced central nervous system tumors using a modified continuous reassessment method: a Pediatric Brain Tumor Consortium Study.
  • PURPOSE: A dose-escalation phase I and pharmacokinetic study of the farnesyltransferase inhibitor lonafarnib (SCH66336) was conducted in children with recurrent or progressive CNS tumors.
  • RESULTS: Fifty-three children with progressive or recurrent brain tumors were enrolled, with a median age of 12.2 years (range, 3.9 to 19.5 years).
  • Both radiographic response (one anaplastic astrocytoma) and stable disease (one medulloblastoma, two high-grade and four low-grade gliomas, one ependymoma, and one sarcoma) were noted, and seven patients remained on treatment for 1 year or longer.
  • [MeSH-major] Central Nervous System Neoplasms / drug therapy. Central Nervous System Neoplasms / mortality. Enzyme Inhibitors / pharmacokinetics. Farnesyltranstransferase / antagonists & inhibitors. Neoplasm Invasiveness / pathology. Piperidines / pharmacokinetics. Pyridines / pharmacokinetics
  • [MeSH-minor] Administration, Oral. Adolescent. Adult. Child. Child, Preschool. Dose-Response Relationship, Drug. Drug Administration Schedule. Female. Follow-Up Studies. Humans. Infant. Infant, Newborn. Male. Maximum Tolerated Dose. Neoplasm Staging. Risk Assessment. Survival Analysis. Treatment Outcome

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  • (PMID = 17634493.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / U01 CA81457
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Enzyme Inhibitors; 0 / Piperidines; 0 / Pyridines; 193275-84-2 / lonafarnib; EC 2.5.1.29 / Farnesyltranstransferase
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2. Badruddoja MA, Keir ST, King I, Zeidner J, Vredenburgh JJ, Muhlbaier LH, Bigner DD, Friedman HS: Activity of VNP40101M (Cloretazine) in the treatment of CNS tumor xenografts in athymic mice. Neuro Oncol; 2007 Jul;9(3):240-4
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  • [Title] Activity of VNP40101M (Cloretazine) in the treatment of CNS tumor xenografts in athymic mice.
  • VNP40101M, or 1,2-bis(methylsulfonyl)-1-(2-choloroethyl)-2-(methylamino)carbonylhydrazine (Cloretazine), is a bifunctional prodrug that belongs to a class of DNA-modifying agents-the sulfonylhydrazines-that has been synthesized and been shown to have activity against a wide spectrum of xenografts.
  • The current study was designed to assess the activity of VNP40101M administered at a dose of 18 mg/kg daily for five days against a panel of human adult and pediatric CNS tumors growing subcutaneously or intracranially in athymic nude mice.
  • The results demonstrated statistically significant (p < 0.05) growth delays of 15.0, 8.3, 51.0, 60+, 60+, and 60+ days in subcutaneous xenografts derived from childhood glioblastoma multiforme (D-456 MG), childhood ependymoma (D-528 EP and D-612 EP), childhood medulloblastoma (D-425 MED), and adult malignant glioma (D-245 MG and D-54 MG), respectively, with corresponding tumor regressions in 10 of 10, 4 of 10, 8 of 10, 9 of 10, 9 of 10, and 10 of 10 treated mice, respectively.
  • Delayed toxicity was seen more than 60 days after treatment, with 23 deaths in 100 treated animals, despite a median weight loss of only 0.06%.
  • Additional experiments conducted against subcutaneous D-245 MG xenografts by using reduced doses of 13.5 or 9.0 mg/kg daily for five days demonstrated tumor growth delays of 82.2 and 53.5 days, with corresponding tumor regressions in 8 of 9 and 9 of 10 treated mice, respectively (all values, p < 0.001), with one toxic death.
  • These findings suggest that VNP40101M is active in the treatment of a wide range of human central nervous system tumors and warrants translation to the clinic.

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  • (PMID = 17522334.001).
  • [ISSN] 1522-8517
  • [Journal-full-title] Neuro-oncology
  • [ISO-abbreviation] Neuro-oncology
  • [Language] ENG
  • [Grant] United States / NINDS NIH HHS / NS / P50 NS020023; United States / NINDS NIH HHS / NS / 5P50-NS20023-23
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Hydrazines; 0 / Prodrugs; 0 / Sulfonamides; 14J2G0U3NQ / laromustine
  • [Other-IDs] NLM/ PMC1907418
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3. Gilbert MR, Ruda R, Soffietti R: Ependymomas in adults. Curr Neurol Neurosci Rep; 2010 May;10(3):240-7
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  • Ependymomas are rare primary central nervous system tumors in adults.
  • They occur most commonly in the spinal cord, where histopathologic evaluation is critical to differentiate the grade I myxopapillary ependymoma from the grade II ependymoma or grade III anaplastic ependymoma.
  • Brain ependymomas are either grade II or III.
  • For myxopapillary ependymoma, complete removal while maintaining capsule integrity may be curative.
  • Radiation commonly is given to the region of tumor, except in cases in which there is imaging or cerebrospinal fluid evidence of tumor dissemination.
  • Ongoing laboratory studies have uncovered important signal transduction pathways that may be better therapeutic targets, leading to the development of clinical trials using targeted agents.
  • [MeSH-major] Central Nervous System Neoplasms. Ependymoma
  • [MeSH-minor] Adult. Epigenesis, Genetic. Humans

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  • (PMID = 20425040.001).
  • [ISSN] 1534-6293
  • [Journal-full-title] Current neurology and neuroscience reports
  • [ISO-abbreviation] Curr Neurol Neurosci Rep
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 62
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4. Gonçalves MI, Radzinsky TC, da Silva NS, Chiari BM, Consonni D: Speech-language and hearing complaints of children and adolescents with brain tumors. Pediatr Blood Cancer; 2008 Mar;50(3):706-8
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  • [Title] Speech-language and hearing complaints of children and adolescents with brain tumors.
  • Central nervous system (CNS) tumors generally leave sequelae that may compromise speech, language, swallowing, hearing, and voice functions.
  • This report describes the incidence of speech-language and hearing complaints and disorders in children and adolescents with CNS tumor under treatment at one of the most important Brazilian reference center for pediatric cancer.
  • [MeSH-major] Brain Neoplasms / complications. Hearing Loss / etiology. Language Disorders / etiology. Speech Disorders / etiology
  • [MeSH-minor] Adolescent. Adult. Antineoplastic Agents / adverse effects. Antineoplastic Agents / therapeutic use. Astrocytoma / complications. Astrocytoma / drug therapy. Child. Child, Preschool. Craniopharyngioma / complications. Craniopharyngioma / drug therapy. Deglutition Disorders / etiology. Ependymoma / complications. Ependymoma / drug therapy. Facial Paralysis / etiology. Female. Humans. Infant. Male. Medulloblastoma / complications. Medulloblastoma / drug therapy


5. Nicholson HS, Kretschmar CS, Krailo M, Bernstein M, Kadota R, Fort D, Friedman H, Harris MB, Tedeschi-Blok N, Mazewski C, Sato J, Reaman GH: Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group. Cancer; 2007 Oct 1;110(7):1542-50
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  • [Title] Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group.
  • BACKGROUND: Effective chemotherapy is lacking for most types of central nervous system (CNS) tumors in children.
  • Temozolomide, an agent with activity against adult brain tumors, was investigated in children and adolescents with recurrent CNS tumors.
  • Patients with a complete (CR) or partial (PR) response or stable disease (SD) could continue temozolomide for up to 12 cycles.
  • RESULTS: The cohort comprised 122 patients, including 113 with CNS tumors.
  • Among 104 evaluable patients with CNS tumors, 5 PRs and 1 CR were observed.
  • PRs occurred in 1 of 23 evaluable patients with high-grade astrocytoma, 1 of 21 with low-grade astrocytoma, and 3 of 25 with medulloblastoma/primitive neuroectodermal tumor (PNET).
  • No responses were observed in patients with ependymoma, brain-stem glioma, or other CNS tumors.
  • [MeSH-major] Antineoplastic Agents, Alkylating / therapeutic use. Brain Neoplasms / drug therapy. Dacarbazine / analogs & derivatives. Neoplasm Recurrence, Local / drug therapy
  • [MeSH-minor] Administration, Oral. Adolescent. Adult. Astrocytoma / drug therapy. Central Nervous System Neoplasms / drug therapy. Child. Child, Preschool. Drug Administration Schedule. Ependymoma / drug therapy. Female. Humans. Infant. Male. Medulloblastoma / drug therapy. Neuroectodermal Tumors, Primitive / drug therapy. Treatment Outcome


6. Brisson C, Lelong-Rebel I, Mottolèse C, Jouvet A, Fèvre-Montange M, Saint Pierre G, Rebel G, Belin MF: Establishment of human tumoral ependymal cell lines and coculture with tubular-like human endothelial cells. Int J Oncol; 2002 Oct;21(4):775-85
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  • Ependymomas, rare neoplasms of the central nervous system, occur predominantly in children.
  • Histological, immunological, and ultrastructural studies showed that the morphological features (microvilli, cilia, and caveolae) of these cultured cells were similar to those of the tumor in vivo.
  • The expression of P-gp, EGF-R, and caveolin-1 by these tumoral ependymocytes could be useful in studies on new drugs.
  • [MeSH-major] Brain Neoplasms / pathology. Cell Culture Techniques / methods. Endothelium, Vascular / cytology. Ependymoma / pathology. Tumor Cells, Cultured
  • [MeSH-minor] Adolescent. Adult. Aged. Cells, Cultured. Child. Child, Preschool. Coculture Techniques. Collagen / pharmacology. Drug Combinations. Female. Humans. Immunohistochemistry. Infant. Laminin / pharmacology. Male. Microscopy, Electron. Microscopy, Fluorescence. Middle Aged. P-Glycoprotein / metabolism. Proteoglycans / pharmacology. Time Factors. Umbilical Veins / cytology

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  • (PMID = 12239616.001).
  • [ISSN] 1019-6439
  • [Journal-full-title] International journal of oncology
  • [ISO-abbreviation] Int. J. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Drug Combinations; 0 / Laminin; 0 / P-Glycoprotein; 0 / Proteoglycans; 119978-18-6 / matrigel; 9007-34-5 / Collagen
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7. Puntoni R, Puntoni M, Ceppi M: Re: Cancer incidence in Denmark following exposure to poliovirus vaccine contaminated with simian virus 40. J Natl Cancer Inst; 2003 Oct 15;95(20):1552-3; author reply 1553-5
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  • [Title] Re: Cancer incidence in Denmark following exposure to poliovirus vaccine contaminated with simian virus 40.
  • [MeSH-major] Neoplasms / epidemiology. Neoplasms / virology. Poliovirus Vaccines / adverse effects. Polyomavirus Infections / complications. Simian virus 40 / isolation & purification. Tumor Virus Infections / complications
  • [MeSH-minor] Adolescent. Adult. Bone Neoplasms / epidemiology. Bone Neoplasms / virology. Central Nervous System Neoplasms / epidemiology. Central Nervous System Neoplasms / virology. Child. Child, Preschool. Cohort Studies. Denmark / epidemiology. Drug Contamination. Ependymoma / epidemiology. Ependymoma / virology. Humans. Incidence. Infant. Mesothelioma / epidemiology. Mesothelioma / virology. Middle Aged. Osteosarcoma / epidemiology. Osteosarcoma / virology

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  • [CommentOn] J Natl Cancer Inst. 2003 Apr 2;95(7):532-9 [12671021.001]
  • (PMID = 14559879.001).
  • [ISSN] 1460-2105
  • [Journal-full-title] Journal of the National Cancer Institute
  • [ISO-abbreviation] J. Natl. Cancer Inst.
  • [Language] eng
  • [Publication-type] Comment; Letter
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Poliovirus Vaccines
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8. Benesch M, Siegler N, Hoff Kv, Lassay L, Kropshofer G, Müller H, Sommer C, Rutkowski S, Fleischhack G, Urban C: Safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with recurrent or refractory brain tumors: a multi-institutional retrospective study. Anticancer Drugs; 2009 Oct;20(9):794-9
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  • [Title] Safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with recurrent or refractory brain tumors: a multi-institutional retrospective study.
  • This retrospective study aimed to evaluate the safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with refractory or recurrent brain tumors.
  • Nineteen heavily pretreated patients (males, n = 14; females, n = 5; median age at diagnosis 8.5 years; range, 1.4-22 years) were given intrathecal liposomal cytarabine on a compassionate use basis for recurrent refractory medulloblastoma (n = 12), mixed germ cell tumor (n = 2), central nervous system primitive neuroectodermal tumors of the pons (n = 1), anaplastic ependymoma (n = 1), anaplastic oligodendroglioma (n = 1), atypical teratoid rhabdoid tumor (n = 1), or rhabdoid papillary meningioma (n = 1).
  • In conclusion, although intrathecal liposomal cytarabine was generally well tolerated, it should be used cautiously and only with dexamethasone prophylaxis in extensively pretreated patients with recurrent brain tumors.
  • Proof of efficacy requires a prospective single-agent phase II study.
  • [MeSH-major] Antimetabolites, Antineoplastic / adverse effects. Brain Neoplasms / drug therapy. Cytarabine / administration & dosage. Cytarabine / adverse effects
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Compassionate Use Trials. Delayed-Action Preparations. Drug Resistance, Neoplasm. Female. Humans. Infant. Injections, Spinal. Liposomes / administration & dosage. Male. Retrospective Studies. Salvage Therapy. Young Adult

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  • (PMID = 19617818.001).
  • [ISSN] 1473-5741
  • [Journal-full-title] Anti-cancer drugs
  • [ISO-abbreviation] Anticancer Drugs
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 0 / Delayed-Action Preparations; 0 / Liposomes; 04079A1RDZ / Cytarabine
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9. Marcus KJ, Goumnerova L, Billett AL, Lavally B, Scott RM, Bishop K, Xu R, Young Poussaint T, Kieran M, Kooy H, Pomeroy SL, Tarbell NJ: Stereotactic radiotherapy for localized low-grade gliomas in children: final results of a prospective trial. Int J Radiat Oncol Biol Phys; 2005 Feb 1;61(2):374-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • PURPOSE: To evaluate the efficacy of stereotactic radiotherapy (SRT) for small, localized, pediatric brain tumors and to determine the patterns of failure.
  • Of the 81 patients, 50 had low-grade astrocytoma, 23 had residual or recurrent craniopharyngioma, 4 had posterior fossa ependymoma, and 4 had other histologic types.
  • All patients underwent biopsy for diagnosis, with the exception of patients with neurofibromatosis and radiographic evidence of an optic system tumor.
  • The target volume generally included the preoperative tumor plus a 2-mm margin for the planning target volume.
  • Five patients, all with optic system/hypothalamic primary tumors, developed central nervous system dissemination 1.0-7.4 years after SRT.
  • One patient developed a presumed radiation-induced primitive neuroectodermal tumor 6 years after initial treatment.
  • Six patients died, three of dissemination, two of progression to higher grade tumors, and one of a secondary radiation-induced tumor.
  • All 6 cases of local progression were within the primary tumor bed at the time of progression and had received the full prescription dose.
  • [MeSH-major] Astrocytoma / surgery. Brain Neoplasms / surgery. Radiosurgery
  • [MeSH-minor] Adolescent. Adult. Child. Child, Preschool. Confidence Intervals. Disease Progression. Disease-Free Survival. Female. Humans. Male. Neoplasm Recurrence, Local / drug therapy. Prospective Studies. Radiotherapy Dosage

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  • (PMID = 15667955.001).
  • [ISSN] 0360-3016
  • [Journal-full-title] International journal of radiation oncology, biology, physics
  • [ISO-abbreviation] Int. J. Radiat. Oncol. Biol. Phys.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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