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Steroids in Palliative Care. A Short Review. Edward (Ted) St. Godard MA CCFP Consultant Physician WRHA Palliative Care. Steroids in Palliative Care. P harmacology C ommon palliative symptoms Role of Steroids Common side-effects. Steroids in Palliative Care. Steroids in Palliative Care.
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Steroids in Palliative Care A Short Review Edward (Ted) St. Godard MA CCFP Consultant Physician WRHA Palliative Care
Steroids in Palliative Care • Pharmacology • Common palliative symptoms • Role of Steroids • Common side-effects
Steroids in Palliative Care • Adrenal medulla: Epinephrine • Adrenal Cortex: Cortisol, aldosterone, dehydroepiandrosterone (DHEA)
Steroids in Palliative Care • Cortisol: • Glucocorticoid secreted by ZonaFasciculata • Numerous physiological effects
Steroids in Palliative Care • Often not significantly better than other therapies for single symptom control (opioids for pain, for instance) • Useful adjuncts in context of multiple symptoms
Steroids in Palliative Care • ~ 60 % PC patients Rx’d steroids • Dexamethasone, 4 – 16 mg/day drug of choice Mercadante et al. “The Use of Steroids in Home Palliative Care.” Support Care Cancer (2001) 9 :386–389
Steroids in Palliative Care • SBGH Jan. – June 2005 • ~ 65 % patients Rx’d steroids during admission • 38 % on steroids at admission • Dexamethasone • Pain, dyspnea, bowel obstruction, brain tumor, SCC Pilkey and Daenicnk. Publication pending
Steroids in Palliative Care • Brain tumor • Dexamethasone and WBRT improves performance status, improves neurological function (short-term benefit) • No current standard dosing based on evidence • Dexamethasone 8 mg bid (4 Qid) Shih et al. “Role of Steroids in Palliative Care.” Journal Pain and Palliative Pharmacotherapy. 21 (4); 2007
Steroids in Palliative Care • Brain tumor • Pain, delirium/dementia, N/V, SZ, motor deficits (all mainly due to increased ICP) • Dexamethasone decreases capillary bed permeability, thus decrease peritumor edema The use and toxicity of Steroids in Mgmt Brain Metastasis.” Support Care Cancer (2008) 16:1041–1048
Steroids in Palliative Care • Malignant bowel obstruction • N/V, pain, global distress • Decrease peri-tumor edema • NNT 6: “Trend toward improvement…” • No evidence of impact on mortality • No dosing recommendations, SE increase with dose Feuer et al. “Systematic review and meta-analysis of corticosteroids for malignant bowel obstruction in advanced gynaecological and gastrointestinal cancers.”Annals of Oncology 10: 1035 - 1041, 1999.
Steroids in Palliative Care • Malignant bowel obstruction • Steroid (Dex: 4 – 16 mg/d) • Metoclopramide • Octreotide Mercadante et al. “Aggressive Pharmacological Treatment for Reversing Malignant Bowel Obstruction.” Journal Pain and Symptom Mgmt. 28:4; 2004
Steroids in Palliative Care • Nausea, emesis • ?reduced permeability BBB to chemicals that induce emesis • Good evidence as adjuncts (with D2 antagonists, 5-HT3 antagonists) • Dexamethasone 4 – 16 mg/d
A B Anorexigenic Neuropeptide Orexigenic Neuropeptide Anorexigenic Neuropeptide Orexigenic Neuropeptide Neurotensin MCH Neurotensin MCH _ _ CNS Cytokinase AGRP CNS Cytokinase Melanocortin AGRP Melanocortin _ CNTF _ IL-1 IL-6 TNF- INF- + _ IL-1 CRF NPY CRF NPY Tryptophan + _ + Seratonin Food Intake Energy Expenditure _ _ + ACTH Food Intake Energy Expenditure Blood Brain Barrier Blood Brain Barrier + Glucocorticoids + _ + IL-6 + + Glucogon Cytokinase Glucogon CNTF IL-1 Leptin CCK Leptin CCK + + + +
A B Anorexigenic Neuropeptide Orexigenic Neuropeptide Anorexigenic Neuropeptide Orexigenic Neuropeptide Neurotensin MCH Neurotensin MCH _ _ CNS Cytokinase AGRP CNS Cytokinase Melanocortin AGRP Melanocortin _ CNTF _ IL-1 IL-6 TNF- INF- + _ IL-1 CRF NPY CRF NPY Tryptophan + _ + Seratonin Food Intake Energy Expenditure _ _ + ACTH Food Intake Energy Expenditure Blood Brain Barrier Blood Brain Barrier + Glucocorticoids + _ + IL-6 + + Glucogon Cytokinase Glucogon CNTF IL-1 Leptin CCK Leptin CCK + + + +
Steroids in Palliative Care • Anorexia • Terribly distressing symptom (worse for families than patients) • Predictive of early demise? Matin and Jatoi. “Megesterol Acetate for the Palliatiation of Anorexia in Advance Incurable Cancer.” Clinical Nutrition. 2006. 25:5
Steroids in Palliative Care • Anorexia and cachexia • Short-term appetite stimulation • Comparable to Megesterol • Lowest dose, pulse, titrate down Matin and Jatoi. “Megesterol Acetate for the Palliatiation of Anorexia in Advance Incurable Cancer.” Clinical Nutrition. 2006. 25:5
Steroids in Palliative Care • Fatigue and depression • Fatigue and “weakness” huge problem • Pulse steroids significantly improve fatigue in number of patients • Short-lived • Side-effects (increased appetite) Lundstrom et al. “The Existential Impact of Starting Steroids in Advanced Metastatic Cancer.” Palliative Medicine. 2009: 23
Steroids in Palliative Care • Fatigue and depression • Depression 15 – 30 % cancer patients • Optimal anti-depressants take too long • Steroids promote sense of “well-being” • Short-lived • Side effects Lundstrom et al. “The Existential Impact of Starting Steroids in Advanced Metastatic Cancer.” Palliative Medicine. 2009: 23
Steroids in Palliative Care • Spinal cord compression • Reduce edema, alleviate pain, improve neurologic outcomes • Some benefit from “high dose,” but significantly increased SE • Dexamethasone 10 mg IV, then 8 mg bid Loblaw et al. J. Clin Oncol. 2005. 23 (30)
Steroids in Palliative Care • SVC syndrome • Often useful in dyspnea 2 airway edema • Steroids as temporizing measure • Chronic use of course leads to SE • Lack of robust evidence base • Dex: dose? Wan et al. “Superior Vena Cave Syndrome.” Emergency clinics North America. 27:2. 2009
Steroids in Palliative Care • Bone pain • Weak evidence base • Strong anecdotal support • Dex 4 – 16 mg/d
Steroids in Palliative Care • Equivocal evidence; STRONG DRUGS • Potential for multiple adverse effects • Clearly dose-related • Many preventable • Most reversible
Steroids in Palliative Care • Hyperglycemia common • Symptoms (polyuria, etc.) • Susceptible to infx, neuropathy • Monitor, treat • Late afternoon capillary glucose
Steroids in Palliative Care • Immune modulation • Compromised patients • Oral candidiasis “Thrush” • Painful and frustrating • Nystatin, fluconazole
Steroids in Palliative Care • GI bleed, gastritis • Potentially catastrophic • Preventable • H2 blocker, PPI
Steroids in Palliative Care • Myopathy • Aches and pains • Weakness • Ambiguous • Decrease dose or discontinue
Steroids in Palliative Care • Miscellaneous • “moon facies,” Cushing • Addissonianism • “Jitters,” poor sleep • Weight gain, voracious appetite • Osteoporosis
Steroids in Palliative Care • Re-cap • Multiple indications • Variable evidence • Good anecdotal support • Dexamethasone PO/IV/SQ • 4 – 16 mg/day • Short term trials • GUT PROTECTION