Steroids in Palliative Care A Short Review Edward (Ted) St. Godard MA CCFP Consultant Physician WRHA...

Steroids in Palliative CareSteroids in Palliative CareA Short ReviewA Short Review

Edward (Ted) St. Godard MA CCFPConsultant PhysicianWRHA Palliative Care

Steroids in Palliative CareSteroids in Palliative Care

• PharmacologyPharmacology

• Common palliative symptomsCommon palliative symptoms

• Role of SteroidsRole of Steroids

• Common side-effectsCommon side-effects



• Adrenal medulla: EpinephrineAdrenal medulla: Epinephrine

• Adrenal Cortex: Cortisol, aldosterone, Adrenal Cortex: Cortisol, aldosterone, dehydroepiandrosterone (DHEA)dehydroepiandrosterone (DHEA)


• Cortisol:Cortisol:• Glucocorticoid secreted by Zona Glucocorticoid secreted by Zona

FasciculataFasciculata• Numerous physiological effectsNumerous physiological effects

Steroids in Palliative CareSteroids in Palliative CareTissue Effects

Liver Increased gluconeogenesisIncreased glycogen synthesis

Skeletal Muscle Decrease glucose uptakeDecrease protein synthesisIncreased protein degradation

Adipose Decrease glucose uptakeIncrease lipid mobilization

General Anti-inflammatory: inhibit phospholipase A2 and production of leukotrienes and prostaglandins


Steroids in Palliative Steroids in Palliative CareCare

• Often not significantly better than Often not significantly better than other therapies for single symptom other therapies for single symptom control (opioids for pain, for control (opioids for pain, for instance)instance)

• Useful adjuncts in context of Useful adjuncts in context of multiple symptomsmultiple symptoms


• ~ 60 % PC patients Rx’d steroids~ 60 % PC patients Rx’d steroids

• Dexamethasone, 4 – 16 mg/day drug of Dexamethasone, 4 – 16 mg/day drug of choicechoice

Mercadante et al. “The Use of Steroids in Home Palliative Care.” Support Care Cancer (2001) 9 :386–389


• SBGH Jan. – June 2005SBGH Jan. – June 2005

• ~ 65 % patients Rx’d steroids ~ 65 % patients Rx’d steroids duringduring admissionadmission

• 38 % on steroids 38 % on steroids atat admission admission

• DexamethasoneDexamethasone

• Pain, dyspnea, bowel obstruction, brain Pain, dyspnea, bowel obstruction, brain tumor, SCCtumor, SCC

Pilkey and Daenicnk. Publication pending

Steroids in Palliative CareSteroids in Palliative Care• Brain tumorBrain tumor

• Dexamethasone and WBRT improves Dexamethasone and WBRT improves performance status, improves neurological performance status, improves neurological function (short-term benefit)function (short-term benefit)

• No current standard dosing based on No current standard dosing based on evidenceevidence

• Dexamethasone 8 mg bid (4 Qid)Dexamethasone 8 mg bid (4 Qid)

Shih et al. “Role of Steroids in Palliative Care.” Journal Pain and Palliative Pharmacotherapy. 21 (4); 2007


• Brain tumorBrain tumor• Pain, delirium/dementia, N/V, SZ, motor Pain, delirium/dementia, N/V, SZ, motor

deficits (all mainly due to increased ICP)deficits (all mainly due to increased ICP)• Dexamethasone decreases capillary bed Dexamethasone decreases capillary bed

permeability, thus decrease peritumor permeability, thus decrease peritumor edemaedema

The use and toxicity of Steroids in Mgmt Brain Metastasis.” Support Care Cancer (2008) 16:1041–1048

Steroids in Palliative CareSteroids in Palliative Care• Malignant bowel obstructionMalignant bowel obstruction

• N/V, pain, global distressN/V, pain, global distress• Decrease peri-tumor edemaDecrease peri-tumor edema• NNT 6: “Trend toward improvement…”NNT 6: “Trend toward improvement…”• No evidence of impact on mortalityNo evidence of impact on mortality• No dosing recommendations, SE increase with No dosing recommendations, SE increase with

dosedose

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 CareSteroids in Palliative Care• Malignant bowel obstructionMalignant bowel obstruction

• Steroid (Dex: 4 – 16 mg/d)Steroid (Dex: 4 – 16 mg/d)• MetoclopramideMetoclopramide• OctreotideOctreotide

Mercadante et al. “Aggressive Pharmacological Treatment for Reversing Malignant Bowel Obstruction.” Journal Pain and Symptom Mgmt. 28:4; 2004


• Nausea, emesisNausea, emesis• ?reduced permeability BBB to ?reduced permeability BBB to

chemicals that induce emesis chemicals that induce emesis • Good evidence as adjuncts (with D2 Good evidence as adjuncts (with D2

antagonists, 5-HT3 antagonists)antagonists, 5-HT3 antagonists)• Dexamethasone 4 – 16 mg/dDexamethasone 4 – 16 mg/d

Anorexigenic Anorexigenic NeuropeptideNeuropeptide

NeurotensinNeurotensin

MelanocortinMelanocortin

CRFCRF

Orexigenic Orexigenic NeuropeptideNeuropeptide

GlucogonGlucogon

CCKCCKLeptinLeptin

Blood Brain BarrierBlood Brain Barrier

NPYNPY

AGRPAGRP

MCHMCH NeurotensinNeurotensin


CRFCRF

GlucogonGlucogon

CCKCCKLeptinLeptin

NPYNPY

AGRPAGRP

MCHMCH

CNS CytokinaseCNS Cytokinase

CytokinaseCytokinase

CNTFCNTFIL-1IL-1


CNTFCNTFIL-1IL-1

Food IntakeFood Intake

Energy ExpenditureEnergy Expenditure Food IntakeFood Intake

Energy ExpenditureEnergy Expenditure

SeratoninSeratonin


IL-6IL-6

TryptophanTryptophan

GlucocorticoidsGlucocorticoids

ACTHACTH



IL-1IL-1IL-6IL-6

TNF-TNF-INF-INF-

__

++

++

++

++

++

++

++

++++

++

++

++

++

__

__

__

____

____

__

AA BB


NeurotensinNeurotensin


CRFCRF


GlucogonGlucogon

CCKCCKLeptinLeptin


NPYNPY

AGRPAGRP

MCHMCH NeurotensinNeurotensin


CRFCRF

GlucogonGlucogon

CCKCCKLeptinLeptin

NPYNPY

AGRPAGRP

MCHMCH


CytokinaseCytokinase

CNTFCNTFIL-1IL-1


CNTFCNTFIL-1IL-1

Food IntakeFood Intake

Energy ExpenditureEnergy Expenditure Food IntakeFood Intake

Energy ExpenditureEnergy Expenditure

SeratoninSeratonin


IL-6IL-6

TryptophanTryptophan

GlucocorticoidsGlucocorticoids

ACTHACTH



IL-1IL-1IL-6IL-6

TNF-TNF-INF-INF-

__

++

++

++

++

++

++

++

++++

++

++

++

++

__

__

__

____

____

__

AA BB


• AnorexiaAnorexia• Terribly distressing symptom (worse for Terribly distressing symptom (worse for

families than patients)families than patients)• Predictive of early demise?Predictive of early demise?

Matin and Jatoi. “Megesterol Acetate for the Palliatiation of Anorexia in Advance Incurable Cancer.” Clinical Nutrition. 2006. 25:5


• Anorexia and cachexiaAnorexia and cachexia• Short-term appetite stimulationShort-term appetite stimulation• Comparable to MegesterolComparable to Megesterol• Lowest dose, pulse, titrate downLowest dose, pulse, titrate down

Matin and Jatoi. “Megesterol Acetate for the Palliatiation of Anorexia in Advance Incurable Cancer.” Clinical Nutrition. 2006. 25:5


• Fatigue and depressionFatigue and depression• Fatigue and “weakness” huge Fatigue and “weakness” huge

problemproblem• Pulse steroids significantly improve Pulse steroids significantly improve

fatigue in number of patientsfatigue in number of patients• Short-livedShort-lived• Side-effects (increased appetite)Side-effects (increased appetite)

Lundstrom et al. “The Existential Impact of Starting Steroids in Advanced Metastatic Cancer.” Palliative Medicine. 2009: 23


• Fatigue and depressionFatigue and depression• Depression 15 – 30 % cancer patientsDepression 15 – 30 % cancer patients• Optimal anti-depressants take too Optimal anti-depressants take too

longlong• Steroids promote sense of “well-Steroids promote sense of “well-

being”being”• Short-livedShort-lived• Side effectsSide effects Lundstrom et al. “The Existential Impact of

Starting Steroids in Advanced Metastatic Cancer.” Palliative Medicine. 2009: 23


• Spinal cord compressionSpinal cord compression• Reduce edema, alleviate pain, improve Reduce edema, alleviate pain, improve

neurologic outcomesneurologic outcomes• Some benefit from “high dose,” but Some benefit from “high dose,” but

significantly increased SEsignificantly increased SE• Dexamethasone 10 mg IV, then 8 mg bidDexamethasone 10 mg IV, then 8 mg bid

Loblaw et al. J. Clin Oncol. 2005. 23 (30)


• SVC syndromeSVC syndrome• Often useful in dyspnea 2 airway edemaOften useful in dyspnea 2 airway edema• Steroids as temporizing measureSteroids as temporizing measure• Chronic use of course leads to SEChronic use of course leads to SE• Lack of robust evidence baseLack of robust evidence base• Dex: dose?Dex: dose?

Wan et al. “Superior Vena Cave Syndrome.”Wan et al. “Superior Vena Cave Syndrome.”

Emergency clinics North America. 27:2. 2009Emergency clinics North America. 27:2. 2009


• Bone painBone pain• Weak evidence baseWeak evidence base• Strong anecdotal supportStrong anecdotal support• Dex 4 – 16 mg/dDex 4 – 16 mg/d


• Equivocal evidence; STRONG DRUGSEquivocal evidence; STRONG DRUGS• Potential for multiple adverse effectsPotential for multiple adverse effects• Clearly dose-relatedClearly dose-related• Many preventableMany preventable• Most reversibleMost reversible







• Hyperglycemia commonHyperglycemia common• Symptoms (polyuria, etc.)Symptoms (polyuria, etc.)• Susceptible to infx, neuropathySusceptible to infx, neuropathy• Monitor, treatMonitor, treat• Late afternoon capillary glucoseLate afternoon capillary glucose







• Immune modulationImmune modulation• Compromised patientsCompromised patients• Oral candidiasis “Thrush”Oral candidiasis “Thrush”• Painful and frustratingPainful and frustrating• Nystatin, fluconazoleNystatin, fluconazole


• GI bleed, gastritisGI bleed, gastritis• Potentially catastrophicPotentially catastrophic• PreventablePreventable• H2 blocker, PPIH2 blocker, PPI







• MyopathyMyopathy• Aches and painsAches and pains• WeaknessWeakness• AmbiguousAmbiguous• Decrease dose or discontinueDecrease dose or discontinue


• Miscellaneous Miscellaneous • ““moon facies,” Cushingmoon facies,” Cushing• AddissonianismAddissonianism• ““Jitters,” poor sleepJitters,” poor sleep• Weight gain, voracious appetiteWeight gain, voracious appetite• OsteoporosisOsteoporosis


• Re-capRe-cap• Multiple indicationsMultiple indications• Variable evidenceVariable evidence• Good anecdotal supportGood anecdotal support• Dexamethasone PO/IV/SQDexamethasone PO/IV/SQ• 4 – 16 mg/day4 – 16 mg/day• Short term trialsShort term trials• GUT PROTECTIONGUT PROTECTION

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Steroids in Palliative Care A Short Review Edward (Ted) St. Godard MA CCFP Consultant Physician WRHA...

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