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Patient with Recurrent Glioblastoma Responding Favorably to Ketogenic Diet Combined with Intranasal Delivery of Perillyl Alcohol: A Case Report and Literature Review
Santos, Juliana Guimarães; Cruz, Wanise Maria Souza Da; Schönthal, Axel H; Salazar, Marcela D'alincourt; Fontes, Cristina Asvolinsque Pantaleão; Quirico-Santos, Thereza; Fonseca, Clovis Orlando da.
  • Santos, Juliana Guimarães; Graduate Program in Medical Sciences, Universidade Federal Fluminense. Niteroi, RJ. BR
  • Cruz, Wanise Maria Souza Da; Department of Nutrition, Universidade Federal Fluminense. Niteroi, RJ. BO
  • Schönthal, Axel H; Department of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California. Los Angeles, CA. US
  • Salazar, Marcela D'alincourt; Department of Experimental Therapeutics, Beckman Research Institute of City of Hope. Duarte, CA. US
  • Fontes, Cristina Asvolinsque Pantaleão; Service of Radiology, Department of Radiology, Antonio Pedro University Hospital, Universidade Federal Fluminense. Niteroi, RJ. BR
  • Quirico-Santos, Thereza; Department of Cellular and Molecular Biology, Institute of Biology, Universidade Federal Fluminense. Niteroi, RJ. BR
  • Fonseca, Clovis Orlando da; Service of Neurosurgery, Department of General and Specialized Surgery, Antonio Pedro University Hospital, Universidade Federal Fluminense. Niteroi, RJ. BR
Arq. bras. neurocir ; 36(3): 194-199, 08/09/2017.
Article in English | LILACS | ID: biblio-911214
ABSTRACT
Introduction Monoterpene perillyl alcohol (POH) is cytotoxic to temozolomideresistant glioma cells, regardless of its O6-methylguanine-methyltransferase (MGMT) promoter methylation status. Moreover, adherence to a ketogenic diet (KD) produced successful outcomes in preclinical and clinical studies in the glioma setting. Case Presentation A 54-year-old Caucasian man had a confirmed diagnosis of refractory glioblastoma multiforme (GBM). The immunohistochemical evaluation was negative for methylation, and failed to detect mutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes. In January 2016, the patient was enrolled in a clinical trial combining daily intranasal delivery of POH in combination with a KD. The KD was administered concomitantly with inhalation of POH (55 mg, 4 times a day) in an uninterrupted administration schedule for 3 months. Results The combination treatment was well-tolerated. The nutritional status and anthropometric measurements of the patient were measured. Adherence to the KD was confirmed by measuring the levels of ketone bodies in the urine. Throughout the treatment, a reduced frequency of seizures was observed. After three months of adherence to the treatment, the patient presented with weight loss, reduced body fat, increased water retention, and a slight increase in bone and muscle mass. A follow-up magnetic resonance imaging (MRI) scan after 3 months of treatment revealed marked reduction of the enhancing lesion. Conclusion Intranasal delivery of POH combined with concomitant adherence to a KD appeared to have a beneficial therapeutic effect in a patient with recurrent GBM. Further studies are needed to evaluate the efficacy of this therapeutic strategy in a larger cohort of treatment-refractory GBM patients.
RESUMO
Introdução O monoterpeno álcool perílico (AP) é citotóxico para linhagens celulares de glioblastoma, independentemente do status do promotor de metilação O6-metilguaninametiltransferase (MGMT). Além disso, a adesão à dieta cetogênica (DC) produziu resultados bem sucedidos em desenho de estudos pré-clínicos e clínicos de glioma. Relato de Caso Homem, 54 anos, caucasiano, com diagnóstico de glioblastoma multiforme (GBM) recidivo. A avaliação imuno-histoquímica foi negativa para metilação e não detectou mutações do gene da isocitrato desidrogenase 1 e 2 (IDH1 IDH2). Em janeiro de 2016, o paciente foi inscrito em um ensaio clínico da administração intranasal diária do AP combinada a DC. A DC foi administrada concomitantemente com inalação de AP (55 mg, 4 vezes ao dia) em um cronograma de administração ininterrupto durante 3 meses. Resultados O tratamento combinado foi bem tolerado. O estado nutricional e as medidas antropométricas do paciente foram avaliadas. Aderência a DC foi confirmada pela presença de corpos cetônicos na urina. Ao longo do tratamento, observou-se redução da frequência de convulsões. Após três meses de adesão ao tratamento, o paciente apresentou perda de peso, redução da gordura corporal, melhor hidratação e um aumento discreto da massa óssea e muscular. O acompanhamento da ressonância magnética após 3 meses de tratamento revelou redução acentuada do volume da lesão. Conclusão A administração intranasal do AP combinada a DC sugere ter um efeito terapêutico benéfico em pacientes com GBM recorrente. São necessários mais estudos para avaliar a eficácia desta estratégia terapêutica em uma coorte maior de pacientes com GBM refratários.
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Full text: Available Index: LILACS (Americas) Main subject: Glioblastoma / Diet, Ketogenic Limits: Humans / Male Language: English Journal: Arq. bras. neurocir Journal subject: Cirurgia / Neurosurgery Year: 2017 Type: Article Affiliation country: Bolivia / Brazil / United States Institution/Affiliation country: Department of Cellular and Molecular Biology, Institute of Biology, Universidade Federal Fluminense/BR / Department of Experimental Therapeutics, Beckman Research Institute of City of Hope/US / Department of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California/US / Department of Nutrition, Universidade Federal Fluminense/BO / Graduate Program in Medical Sciences, Universidade Federal Fluminense/BR / Service of Neurosurgery, Department of General and Specialized Surgery, Antonio Pedro University Hospital, Universidade Federal Fluminense/BR / Service of Radiology, Department of Radiology, Antonio Pedro University Hospital, Universidade Federal Fluminense/BR

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Full text: Available Index: LILACS (Americas) Main subject: Glioblastoma / Diet, Ketogenic Limits: Humans / Male Language: English Journal: Arq. bras. neurocir Journal subject: Cirurgia / Neurosurgery Year: 2017 Type: Article Affiliation country: Bolivia / Brazil / United States Institution/Affiliation country: Department of Cellular and Molecular Biology, Institute of Biology, Universidade Federal Fluminense/BR / Department of Experimental Therapeutics, Beckman Research Institute of City of Hope/US / Department of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California/US / Department of Nutrition, Universidade Federal Fluminense/BO / Graduate Program in Medical Sciences, Universidade Federal Fluminense/BR / Service of Neurosurgery, Department of General and Specialized Surgery, Antonio Pedro University Hospital, Universidade Federal Fluminense/BR / Service of Radiology, Department of Radiology, Antonio Pedro University Hospital, Universidade Federal Fluminense/BR