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Safety, Tolerability, and Use of Steroids

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Central Nervous System Metastases

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Abstract

Steroid treatment for patients with brain metastases was established in the 1950s [1, 2] and remains the primary choice for the treatment of peritumoral brain edema. The anti-edema effects of steroids provide quick and reliable, though transient, relief from intracranial mass effect and associated symptoms. In this chapter, an overview on the pathomechanism of tumor-related edema as well as the effects, pharmacokinetics, and most important side effects of steroids will be provided.

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References

  1. Galicich JH, French LA, Melby JC. Use of dexamethasone in treatment of cerebral edema associated with brain tumors. J Lancet. 1961;81:46–53.

    CAS  PubMed  Google Scholar 

  2. Ingraham FD, Matson DD, Mc LR. Cortisone and ACTH as an adjunct to the surgery of craniopharyngiomas. N Engl J Med. 1952;246:568–71.

    Article  CAS  PubMed  Google Scholar 

  3. Murayi R, Chittiboina P. Glucocorticoids in the management of peritumoral brain edema: a review of molecular mechanisms. Childs Nerv Syst. 2016;32:2293–302.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Roth P, et al. Tumor-associated edema in brain cancer patients: pathogenesis and management. Expert Rev Anticancer Ther. 2013;13:1319–25.

    Article  CAS  PubMed  Google Scholar 

  5. Liebner S, et al. Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme. Acta Neuropathol. 2000;100:323–31.

    Article  CAS  PubMed  Google Scholar 

  6. Salvador E, Burek M, Forster CY. Tight junctions and the tumor microenvironment. Curr Pathobiol Rep. 2016;4:135–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Saadoun S, et al. Increased aquaporin 1 water channel expression in human brain tumours. Br J Cancer. 2002;87:621–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cifone MG, et al. Dexamethasone-induced thymocyte apoptosis: apoptotic signal involves the sequential activation of phosphoinositide-specific phospholipase C, acidic sphingomyelinase, and caspases. Blood. 1999;93:2282–96.

    Article  CAS  PubMed  Google Scholar 

  9. Gilardini Montani MS, et al. Dexamethasone induces apoptosis in human T cell clones expressing low levels of Bcl-2. Cell Death Differ. 1999;6:79–86.

    Article  CAS  PubMed  Google Scholar 

  10. Herold MJ, McPherson KG, Reichardt HM. Glucocorticoids in T cell apoptosis and function. Cell Mol Life Sci. 2006;63:60–72.

    Article  CAS  PubMed  Google Scholar 

  11. Hegeman MA, et al. Dexamethasone attenuates VEGF expression and inflammation but not barrier dysfunction in a murine model of ventilator-induced lung injury. PLoS One. 2013;8:e57374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Heiss JD, et al. Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats. Involvement of the glucocorticoid receptor and vascular permeability factor. J Clin Invest. 1996;98:1400–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Liu DR, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9(1):30.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ly KI, Wen PY. Clinical relevance of steroid use in neuro-oncology. Curr Neurol Neurosci Rep. 2017;17:5.

    Article  PubMed  CAS  Google Scholar 

  15. Roth P, Happold C, Weller M. Corticosteroid use in neuro-oncology: an update. Neurooncol Pract. 2015;2:6–12.

    PubMed  Google Scholar 

  16. Barnes PJ. Molecular mechanisms and cellular effects of glucocorticosteroids. Immunol Allergy Clin N Am. 2005;25:451.

    Article  Google Scholar 

  17. Nicolaides NC, et al. The human glucocorticoid receptor: molecular basis of biologic function. Steroids. 2010;75:1–12.

    Article  CAS  PubMed  Google Scholar 

  18. Schaaf MJM, Cidlowski JA. Molecular mechanisms of glucocorticoid action and resistance. J Steroid Biochem Mol Biol. 2002;83:37–48.

    Article  CAS  PubMed  Google Scholar 

  19. Hadjidimos A, et al. Effects of dexamethasone on Rcbf and cerebral vasomotor response in brain tumors—preliminary communication. Eur Neurol. 1973;10:25–30.

    Article  CAS  PubMed  Google Scholar 

  20. Hazlewood KA, Fugate SE, Harrison DL. Effect of oral corticosteroids on chronic warfarin therapy. Ann Pharmacother. 2006;40:2101–6.

    Article  CAS  PubMed  Google Scholar 

  21. Chalk JB, et al. Phenytoin impairs the bioavailability of dexamethasone in neurological and neurosurgical patients. J Neurol Neurosurg Psychiatry. 1984;47:1087–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lawson LA, et al. Phenytoin-dexamethasone interaction: a previously unreported observation. Surg Neurol. 1981;16:23–4.

    Article  CAS  PubMed  Google Scholar 

  23. Svalheim S, et al. Interactions between antiepileptic drugs and hormones. Seizure. 2015;28:12–7.

    Article  PubMed  Google Scholar 

  24. Werk EE Jr, et al. Interference in the effect of dexamethasone by diphenylhydantoin. N Engl J Med. 1969;281:32–4.

    Article  PubMed  Google Scholar 

  25. Zhang YY, Yang L. Interactions between human cytochrome P450 enzymes and steroids: physiological and pharmacological implications. Expert Opin Drug Metab Toxicol. 2009;5:621–9.

    Article  CAS  PubMed  Google Scholar 

  26. Chu CC, et al. The cellular mechanisms of the antiemetic action of dexamethasone and related glucocorticoids against vomiting. Eur J Pharmacol. 2014;722:48–54.

    Article  CAS  PubMed  Google Scholar 

  27. Crocker EF, et al. Effect of steroids on extravascular distribution of radiographic contrast material and technetium pertechnetate in brain tumors as determined by computed tomography. Radiology. 1976;119:471–4.

    Article  CAS  PubMed  Google Scholar 

  28. Kullberg G, West KA. Influence of corticosteroids on ventricular fluid pressure. Acta Neurol Scand Suppl. 1965;41:445.

    Article  Google Scholar 

  29. Miller JD, Leech P. Effects of mannitol and steroid-therapy on intracranial volume-pressure relationships in patients. J Neurosurg. 1975;42:274–81.

    Article  CAS  PubMed  Google Scholar 

  30. Weinstein JD, et al. Effect of dexamethasone on brain edema in patients with metastatic brain tumors. Neurology. 1973;23:121–9.

    Article  CAS  PubMed  Google Scholar 

  31. Armitage PA, et al. Quantitative assessment of intracranial tumor response to dexamethasone using diffusion, perfusion and permeability magnetic resonance imaging. Magn Reson Imaging. 2007;25:303–10.

    Article  CAS  PubMed  Google Scholar 

  32. Bastin ME, et al. The use of diffusion tensor imaging in quantifying the effect of dexamethasone on brain tumours. Neuroreport. 1999;10:1385–91.

    Article  CAS  PubMed  Google Scholar 

  33. Watling CJ, et al. Corticosteroid-induced magnetic-resonance-imaging changes in patients with recurrent malignant glioma. J Clin Oncol. 1994;12:1886–9.

    Article  CAS  PubMed  Google Scholar 

  34. Grossman E, Messerli FH. Drug-induced hypertension: an unappreciated cause of secondary hypertension. Am J Med. 2012;125:14–22.

    Article  CAS  PubMed  Google Scholar 

  35. Pimenta E, Wolley M, Stowasser M. Adverse cardiovascular outcomes of corticosteroid excess. Endocrinology. 2012;153:5137–42.

    Article  CAS  PubMed  Google Scholar 

  36. Coelho MC, et al. Adverse effects of glucocorticoids: coagulopathy. Eur J Endocrinol. 2015;173:M11–21.

    Article  CAS  PubMed  Google Scholar 

  37. Cote DJ, et al. Venous thromboembolism in patients undergoing craniotomy for brain tumors: a U.S. Nationwide analysis. Semin Thromb Hemost. 2016;42:870–6.

    Article  PubMed  Google Scholar 

  38. Lansang MC, Hustak LK. Glucocorticoid-induced diabetes and adrenal suppression: how to detect and manage them. Cleve Clin J Med. 2011;78:748–56.

    Article  PubMed  Google Scholar 

  39. Garber AJ, et al. American Association of Clinical Endocrinologists’ comprehensive diabetes management algorithm 2013 consensus statement—executive summary. Endocr Pract. 2013;19:536–57.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Narum S, Westergren T, Klemp M. Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ Open. 2014;4:e004587.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Butler E, et al. Corticosteroids and risk of gastrointestinal bleeding in critically ill adults: protocol for a systematic review. Acta Anaesthesiol Scand. 2018;62:1321–6.

    Article  CAS  PubMed  Google Scholar 

  42. Henson JW, et al. Pneumocystis-carinii pneumonia in patients with primary brain-tumors. Arch Neurol. 1991;48:406–9.

    Article  CAS  PubMed  Google Scholar 

  43. Cooley L, et al. Consensus guidelines for diagnosis, prophylaxis and management of Pneumocystis jirovecii pneumonia in patients with haematological and solid malignancies, 2014. Intern Med J. 2014;44:1350–63.

    Article  CAS  PubMed  Google Scholar 

  44. Mathew BS, Grossman SA. Pneumocystis carinii pneumonia prophylaxis in HIV negative patients with primary CNS lymphoma. Cancer Treat Rev. 2003;29:105–19.

    Article  PubMed  Google Scholar 

  45. Schiff D. Pneumocystis pneumonia in brain tumor patients: risk factors and clinical features. J Neuro-Oncol. 1996;27:235–40.

    Article  CAS  Google Scholar 

  46. Overgaard UM, Helweg-Larsen J. Pneumocystis jiroveci pneumonia (PCP) in HIV-1-negative patients: a retrospective study 2002–2004. Scand J Infect Dis. 2007;39:589–95.

    Article  PubMed  Google Scholar 

  47. Bowyer SL, LaMothe MP, Hollister JR. Steroid myopathy: incidence and detection in a population with asthma. J Allergy Clin Immunol. 1985;76:234–42.

    Article  CAS  PubMed  Google Scholar 

  48. Dropcho EJ, Soong SJ. Steroid-induced weakness in patients with primary brain tumors. Neurology. 1991;41:1235–9.

    Article  CAS  PubMed  Google Scholar 

  49. Minetto MA, et al. Diagnostic work-up in steroid myopathy. Endocrine. 2018;60:219–23.

    Article  CAS  PubMed  Google Scholar 

  50. Pereira RM, Freire de Carvalho J. Glucocorticoid-induced myopathy. Joint Bone Spine. 2011;78:41–4.

    Article  CAS  PubMed  Google Scholar 

  51. Dirks-Naylor AJ, Griffiths CL. Glucocorticoid-induced apoptosis and cellular mechanisms of myopathy. J Steroid Biochem Mol Biol. 2009;117:1–7.

    Article  CAS  PubMed  Google Scholar 

  52. Schakman O, Gilson H, Thissen JP. Mechanisms of glucocorticoid-induced myopathy. J Endocrinol. 2008;197:1–10.

    Article  CAS  PubMed  Google Scholar 

  53. Anagnos A, Ruff RL, Kaminski HJ. Endocrine neuromyopathies. Neurol Clin. 1997;15:673–96.

    Article  CAS  PubMed  Google Scholar 

  54. Alshekhlee A, Kaminski HJ, Ruff RL. Neuromuscular manifestations of endocrine disorders. Neurol Clin. 2002;20:35–58.. v-vi

    Article  PubMed  Google Scholar 

  55. Grossman JM, et al. American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken). 2010;62:1515–26.

    Article  Google Scholar 

  56. Blake GM, Fogelman I. Bone densitometry, steroids and osteoporosis. Curr Opin Nephrol Hypertens. 2002;11:641–7.

    Article  PubMed  Google Scholar 

  57. Lipton A. New therapeutic agents for the treatment of bone diseases. Expert Opin Biol Ther. 2005;5:817–32.

    Article  CAS  PubMed  Google Scholar 

  58. Aghayev K, Papanastassiou ID, Vrionis F. Role of vertebral augmentation procedures in the management of vertebral compression fractures in cancer patients. Curr Opin Support Palliat Care. 2011;5:222–6.

    Article  PubMed  Google Scholar 

  59. Mahar S, Malhotra M. Dexamethasone-induced withdrawal seizure. J Pharmacol Pharmacother. 2015;6:103–4.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Bolanos SH, et al. Assessment of mood states in patients receiving long-term corticosteroid therapy and in controls with patient-rated and clinician-rated scales. Ann Allergy Asthma Immunol. 2004;92:500–5.

    Article  PubMed  Google Scholar 

  61. Lewis DA, Smith RE. Steroid-induced psychiatric syndromes. A report of 14 cases and a review of the literature. J Affect Disord. 1983;5:319–32.

    Article  CAS  PubMed  Google Scholar 

  62. Brown ES, et al. Mood changes during prednisone bursts in outpatients with asthma. J Clin Psychopharmacol. 2002;22:55–61.

    Article  PubMed  Google Scholar 

  63. Sonino N, et al. Clinical correlates of major depression in Cushing’s disease. Psychopathology. 1998;31:302–6.

    Article  CAS  PubMed  Google Scholar 

  64. Kullmann MK, et al. The p27-Skp2 axis mediates glucocorticoid-induced cell cycle arrest in T-lymphoma cells. Cell Cycle. 2013;12:2625–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Sionov RV, et al. Mechanisms regulating the susceptibility of hematopoietic malignancies to glucocorticoid-induced apoptosis. Adv Cancer Res. 2008;101:127–248.

    Article  CAS  PubMed  Google Scholar 

  66. Vecht CJ, et al. Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors: a randomized study of doses of 4, 8, and 16 mg per day. Neurology. 1994;44:675–80.

    Article  CAS  PubMed  Google Scholar 

  67. Soffietti R, et al. Diagnosis and treatment of brain metastases from solid tumors: guidelines from the European Association of Neuro-Oncology (EANO). Neuro-Oncology. 2017;19:162–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Alan N, et al. Preoperative steroid use and the incidence of perioperative complications in patients undergoing craniotomy for definitive resection of a malignant brain tumor. J Clin Neurosci. 2015;22:1413–9.

    Article  CAS  PubMed  Google Scholar 

  69. Renfro L, Snow JS. Ocular effects of topical and systemic steroids. Dermatol Clin. 1992;10:505–12.

    Article  CAS  PubMed  Google Scholar 

  70. Hodi FS, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Tawbi HA, et al. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med. 2018;379:722–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Xing K, et al. Dexamethasone enhances programmed cell death 1 (PD-1) expression during T cell activation: an insight into the optimum application of glucocorticoids in anti-cancer therapy. BMC Immunol. 2015;16:39.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Villadolid J, Amin A. Immune checkpoint inhibitors in clinical practice: update on management of immune-related toxicities. Transl Lung Cancer Res. 2015;4:560–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Fecher LA, et al. Ipilimumab and its toxicities: a multidisciplinary approach. Oncologist. 2013;18:733–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Weber JS. Practical management of immune-related adverse events from immune checkpoint protein antibodies for the oncologist. Am Soc Clin Oncol Educ Book. 2012;2012:174–7.

    Google Scholar 

  76. Chinot OL, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370:709–22.

    Article  CAS  PubMed  Google Scholar 

  77. Wick W, et al. Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med. 2017;377:1954–63.

    Article  CAS  PubMed  Google Scholar 

  78. Wirsching HG, et al. Bevacizumab plus hypofractionated radiotherapy versus radiotherapy alone in elderly patients with glioblastoma: the randomized, open-label, phase II ARTE trial. Ann Oncol. 2018;29:1423–30.

    Article  PubMed  Google Scholar 

  79. Boothe D, et al. Bevacizumab as a treatment for radiation necrosis of brain metastases post stereotactic radiosurgery. Neuro-Oncology. 2013;15:1257–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Fanous AA, Fabiano AJ. Bevacizumab for the treatment of post-stereotactic radiosurgery adverse radiation effect. Surg Neurol Int. 2016;7:S542–4.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Levin VA, et al. Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys. 2011;79:1487–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Recht L, et al. Steroid-sparing effect of corticorelin acetate in peritumoral cerebral edema is associated with improvement in steroid-induced myopathy. J Clin Oncol. 2013;31:1182–7.

    Article  CAS  PubMed  Google Scholar 

  83. Schneider H, Weller M. Boswellic acid activity against glioblastoma stem-like cells. Oncol Lett. 2016;11:4187–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kirste S, et al. Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: a prospective, randomized, placebo-controlled, double-blind pilot trial. Cancer. 2011;117:3788–95.

    Article  PubMed  Google Scholar 

  85. Roy NK, et al. The potential role of boswellic acids in cancer prevention and treatment. Cancer Lett. 2016;377:74–86.

    Article  CAS  PubMed  Google Scholar 

  86. Pitter KL, et al. Corticosteroids compromise survival in glioblastoma. Brain. 2016;139:1458–71.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology and Brain Tumor Center Zurich, University Hospital Zurich and University of Zurich, Zurich, Switzerland

    Fabian Wolpert & Patrick Roth

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  1. Fabian Wolpert
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  2. Patrick Roth
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Correspondence to Patrick Roth .

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Editors and Affiliations

  1. Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH, USA

    Manmeet Ahluwalia

  2. Department of Neurosurgery and Neuro-Oncology, Clairval Hospital Center, Ramsay-Générale de Santé, Marseille, France, Neurophysiopathology Institute, Aix-Marseille Université, Marseille, France

    Philippe Metellus

  3. Department of Neuro-Oncology, University and City of Health and Science Hospital, Turin, Italy

    Riccardo Soffietti

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Wolpert, F., Roth, P. (2020). Safety, Tolerability, and Use of Steroids. In: Ahluwalia, M., Metellus, P., Soffietti, R. (eds) Central Nervous System Metastases. Springer, Cham. https://doi.org/10.1007/978-3-030-23417-1_10

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  • DOI: https://doi.org/10.1007/978-3-030-23417-1_10

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