Subscribe to RSS
DOI: 10.1055/s-0037-1605588
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 literaturaPublication History
01 June 2017
11 July 2017
Publication Date:
10 August 2017 (online)
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.
-
References
- 1 Stupp R, Mason WP, van den Bent MJ. , et al; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352 (10) 987-996
- 2 Durst CR, Raghavan P, Shaffrey ME. , et al. Multimodal MR imaging model to predict tumor infiltration in patients with gliomas. Neuroradiology 2014; 56 (02) 107-115
- 3 Paw I, Carpenter RC, Watabe K, Debinski W, Lo HW. Mechanisms regulating glioma invasion. Cancer Lett 2015; 362 (01) 1-7
- 4 Wu CX, Lin GS, Lin ZX. , et al. Peritumoral edema on magnetic resonance imaging predicts a poor clinical outcome in malignant glioma. Oncol Lett 2015; 10 (05) 2769-2776
- 5 Armstrong TS, Grant R, Gilbert MR, Lee JW, Norden AD. Epilepsy in glioma patients: mechanisms, management, and impact of anticonvulsant therapy. Neuro-oncol 2016; 18 (06) 779-789
- 6 Bruna J, Miró J, Velasco R. Epilepsy in glioblastoma patients: basic mechanisms and current problems in treatment. Expert Rev ClinPharmacol 2013; 6 (03) 333-344
- 7 Kargiotis O, Markoula S, Kyritsis AP. Epilepsy in the cancer patient. Cancer ChemotherPharmacol 2011; 67 (03) 489-501
- 8 Pallud J, Capelle L, Huberfeld G. Tumoralepileptogenicity: how does it happen?. Epilepsia 2013; 54 (Suppl. 09) 30-34
- 9 Shamji MF, Fric-Shamji EC, Benoit BG. Brain tumors and epilepsy: pathophysiology of peritumoral changes. Neurosurg Rev 2009; 32 (03) 275-284 , discussion 284–286
- 10 Allen BG, Bhatia SK, Anderson CM. , et al. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism. Redox Biol 2014; 2: 963-970
- 11 Cross H. Epilepsy: behavioural, psychological, and ketogenic diet treatments. BMJ ClinEvid 2015
- 12 Rho JM. How does the ketogenic diet induce anti-seizure effects?. Neurosci Lett 2017; 637: 4-10
- 13 Strowd III RE, Grossman SA. The Role of Glucose Modulation and Dietary Supplementation in Patients With Central Nervous System Tumors. Curr Treat Options Oncol 2015; 16 (08) 36
- 14 Mobbs CV, Mastaitis J, Isoda F, Poplawski M. Treatment of diabetes and diabetic complications with a ketogenic diet. J Child Neurol 2013; 28 (08) 1009-1014
- 15 Paoli A, Bianco A, Damiani E, Bosco G. Ketogenic diet in neuromuscular and neurodegenerative diseases. BioMed Res Int 2014; 2014: 474296
- 16 Champ CE, Palmer JD, Volek JS. , et al. Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. J Neurooncol 2014; 117 (01) 125-131
- 17 Seyfried TN, Flores R, Poff AM, D'Agostino DP, Mukherjee P. Metabolic therapy: a new paradigm for managing malignant brain cancer. Cancer Lett 2015; 356 (2 Pt A): 289-300
- 18 Liberti MV, Locasale JW. The Warburg Effect: How Does it Benefit Cancer Cells?. Trends Biochem Sci 2016; 41 (03) 211-218
- 19 Lu J, Tan M, Cai Q. The Warburg effect in tumor progression: mitochondrial oxidative metabolism as an anti-metastasis mechanism. Cancer Lett 2015; 356 (2 Pt A): 156-164
- 20 Bhattacharya B, Mohd Omar MF, Soong R. The Warburg effect and drug resistance. Br J Pharmacol 2016; 173 (06) 970-979
- 21 Kroemer G, Pouyssegur J. Tumor cell metabolism: cancer's Achilles' heel. Cancer Cell 2008; 13 (06) 472-482
- 22 Zuccoli G, Marcello N, Pisanello A. , et al. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report. NutrMetab (Lond) 2010; 7: 33
- 23 Schwartz K, Chang HT, Nikolai M. , et al. Treatment of glioma patients with ketogenic diets: report of two cases treated with an IRB-approved energy-restricted ketogenic diet protocol and review of the literature. Cancer Metab 2015; 3: 3
- 24 da Fonseca CO, Linden R, Futur oD, Gattass CR, Quirico-Santos T. Ras pathway activation in gliomas: a strategic target for intranasal administration of perillyl alcohol. Arch ImmunolTherExp (Warsz) 2008; 56 (04) 267-276
- 25 Da Fonseca CO, Silva JT, Lins IR. , et al. Correlation of tumor topography and peritumoral edema of recurrent malignant gliomas with therapeutic response to intranasal administration of perillyl alcohol. Invest New Drugs 2009; 27 (06) 557-564
- 26 DA Fonseca CO, Teixeira RM, Silva JC. , et al. Long-term outcome in patients with recurrent malignant glioma treated with Perillyl alcohol inhalation. Anticancer Res 2013; 33 (12) 5625-5631
- 27 Wagner M, Moore DD. Endoplasmic reticulum stress and glucose homeostasis. CurrOpinClinNutrMetab Care 2011; 14 (04) 367-373
- 28 Schonthal AH. Targeting endoplasmic reticulum stress for cancer therapy. Front Biosci (Schol Ed) 2012; 4: 412-431
- 29 Kato H, Nishitoh H. Stress responses from the endoplasmic reticulum in cancer. Front Oncol 2015; 5: 93
- 30 Peñaranda Fajardo NM, Meijer C, Kruyt FA. The endoplasmic reticulum stress/unfolded protein response in gliomagenesis, tumor progression and as a therapeutic target in glioblastoma. BiochemPharmacol 2016; 118: 1-8
- 31 Cho HY, Wang W, Jhaveri N. , et al. Perillyl alcohol for the treatment of temozolomide-resistant gliomas. Mol Cancer Ther 2012; 11 (11) 2462-2472
- 32 Henker C, Kriesen T, Fürst K. , et al. Effect of 10 different polymorphisms on preoperative volumetric characteristics of glioblastoma multiforme. J Neurooncol 2016; 126 (03) 585-592
- 33 Brazilian Cardiology Archives. Brazilian guideline of dyslipidemia and prevention of atherosclerosis. Available in: http://publicações.cardiol.br/2014/diretrizes.asp . Acess 2016 (November/11).
- 34 Zidlik V, Brychtova S, Uvirova M, Ziak D, Dvorackova J. The changes of angiogenesis and immune cell infiltration in the intra- and peri-tumoral melanoma microenvironment. Int J MolSci 2015; 16 (04) 7876-7889
- 35 Woolf EC, Curley KL, Liu Q. , et al. The Ketogenic Diet Alters the Hypoxic Response and Affects Expression of Proteins Associated with Angiogenesis, Invasive Potential and Vascular Permeability in a Mouse Glioma Model. PLoS One 2015; 10 (06) e0130357
- 36 Lin ZX. Glioma-related edema: new insight into molecular mechanisms and their clinical implications. Chin J Cancer 2013; 32 (01) 49-52
- 37 Sampaio LP. Ketogenic diet for epilepsy treatment. ArqNeuropsiquiatr 2016; 74 (10) 842-848
- 38 Kaur T, Manchanda S, Saini V, Lakhman SS, Kaur G. Efficacy of Anti-Epileptic Drugs in the Treatment of Tumor and Its Associated Epilepsy: An in vitro Perspective. Ann Neurosci 2016; 23 (01) 33-43
- 39 Lillis KP, Dulla C, Maheshwari A. , et al. WONOEP appraisal: molecular and cellular imaging in epilepsy. Epilepsia 2015; 56 (04) 505-513