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CC BY-NC-ND 4.0 · Arquivos Brasileiros de Neurocirurgia: Brazilian Neurosurgery 2017; 36(03): 194-199
DOI: 10.1055/s-0037-1605588
Case Report | Relato de Caso
Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil

Patient with Recurrent Glioblastoma Responding Favorably to Ketogenic Diet Combined with Intranasal Delivery of Perillyl Alcohol: A Case Report and Literature Review

Paciente com glioblastoma recorrente respondendo positivamente a dieta cetogênica combinada a álcool perílico intranasal: relato de caso e revisão da literatura
Juliana Guimarães Santos
1   Graduate Program in Medical Sciences, Universidade Federal Fluminense, Niteroi, RJ, Brazil
,
Wanise Maria Souza Da Cruz
2   Department of Nutrition, Universidade Federal Fluminense, Niteroi, RJ, Brazil
,
Axel H. Schönthal
3   Department of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California, Los Angeles, USA
,
Marcela D'alincourt Salazar
4   Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA91010, USA
,
Cristina Asvolinsque Pantaleão Fontes
5   Service of Radiology, Department of Radiology, Antonio Pedro University Hospital, Universidade Federal Fluminense, Niteroi, RJ, Brazil
,
Thereza Quirico-Santos
6   Department of Cellular and Molecular Biology, Institute of Biology, Universidade Federal Fluminense, Niteroi, RJ, Brazil
,
Clovis Orlando da Fonseca
7   Service of Neurosurgery, Department of General and Specialized Surgery, Antonio Pedro University Hospital, Universidade Federal Fluminense, Niteroi, RJ, Brazil
› Institutsangaben
Weitere Informationen

Publikationsverlauf

01. Juni 2017

11. Juli 2017

Publikationsdatum:
10. August 2017 (online)

   Lizenzen und Reprints

Abstract

Introduction Monoterpene perillyl alcohol (POH) is cytotoxic to temozolomide-resistant 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-metilguanina-metiltransferase (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.

Keywords

ketogenic diet - perillyl alcohol - intranasal administration - glioblastoma multiforme - combination therapy - drug resistance

Palavras-chave

dieta cetogênica - álcool perílico - administração intranasal - glioblastoma multiforme - tratamento combinado - resistência medicamentosa
 

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