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“Top Ten” Clinical Tips on Symptom
Management for Patients with
Advanced Cancer
Dr. José Pereira
Head Division of Palliative Care, University of Ottawa
Medical Chief, Palliative Care Service, Bruyère Continuing Care & The
Ottawa Hospital
Provincial Medical Lead for Palliative Care, Cancer Care Ontario
Dr. Sandy Buchman
Palliative Care Consultant, Temmy Latner Centre, Toronto
& University of Toronto
Quality & Primary Care Engagement Lead, Palliative Care Program, Cancer
Care Ontario
Faculty/Presenter Disclosure
 Faculty: Dr. José Pereira
 Program: 51st Annual Scientific Assembly
 Relationship with commercial interests:
– Grants/Research Support: Takeda (past) Education grant to
conduct review of breakthrough pain
– Speakers Bureau/honoraria: Nil to report
– Consulting Fees: Nil to report
– Other: Nil to report
Disclosure of Commercial Support
 This program has NOT received financial support
 This program has NOT received in-kind support
(except for myself and my organization who have
allowed me to be here to present on their time)
 No potential for conflict(s) of interest to declare
Mitigating potential bias
 Jose Pereira
– Takeda: Product has very limited role & prohibitively
expensive
Faculty/Presenter Disclosure
 Faculty: Dr. Sandy Buchman
 Program: 51st Annual Scientific Assembly
 Relationship with commercial interests:
–
–
–
–
Grants/Research Support: Nil to report
Speakers Bureau/honoraria: Nil to report
Consulting Fees: Nil to report
Other: Nil to report
Disclosure of Commercial Support
 This program has NOT received financial support
 This program has NOT received in-kind support
(except for myself and my organization who have
allowed me to be here to present on their time)
 No potential for conflict(s) of interest to declare
Mitigating potential bias
 Sandy Buchman
– Nil to declare
Any burning questions??
1. Systematic Screening of Symptoms
Cancer patients experience many symptoms across
the illness trajectory
Symptom Intensity & Tumor Stage (Non-hematological cancers)
N= 240
Median # of
symptoms = 8 per
patient
No
evidence
of
disease
Local
disease
Regional
disease
Metastatic
disease
No. of symptoms
9 (0-24)
7 (0-17)
6 (0-15)
10 (0-25)
Moderate to severe
symptoms
4 (0-14)
3 (0-12)
3 (0-12)
6 (0-20)
Chang VT et al. Symptom and Quality of Life Survey of Medical Oncology Patients: A Role for Symptom
Assessment. Cancer 2000;88:1175-1183
Symptoms are under-reported by patients
unless standardized questionnaire used
White C, et al. ‘‘Now that You Mention it, Doctor . . . ’’:Symptom Reporting and the
Need for Systematic Questioning in a Specialist Palliative Care Unit, J Pall Med
2009; 12(5):447-450
Symptoms: Patient reporting versus systematic
assessment
 Total symptoms
identified: 2,397
– Of these, only 14%
(322) were
volunteered
Homsi J, et al. Symptom evaluation in palliative medicine: Patient report vs
systematic assessment. Support Care Cancer 2006;14:444–453.
Edmonton Symptom Assessment Scale (ESAS)
ISAAC II
• ESAS R
• Patient Self-Report
Functional Status (ECOG)
• Additional questions
• Beginning process of
tailoring kiosk to clinics &
needs
Clinicians can fail to
recognize 50-80%
of patients
concerns during
consultation
Significantly
reduced symptom
distress across a
number of
symptoms
2. Useful Clinical Tools
The Palliative Performance Scale (PPS)
Palliative Performance Scale (PPS)
ECOG
Stable
0
%
Ambulation
Activity & Evidence of
Disease
Self-Care
Intake
Level of
Consciousness
100
Full
Normal activity
No evidence of disease
Full
Normal
Full
90
Full
Normal activity
Evidence of disease
Full
Normal
Full
80
Full
Normal activity with effort
Evidence of disease
Full
Normal/
Reduced
Full
70
Reduced
Unable to do normal work
Evidence of disease
Full
Normal/
Reduced
Full
60
Reduced
Unable to do house work
Significant disease
Occasional
Assistance
Normal/
Reduced
Full or
Confusion
50
Mainly
Sit/Lie
Unable to do any work
Evidence of disease
Considerable
Assistance
Normal/
Reduced
Full or
Confusion
40
Mainly in
Bed
As Above
Mainly
Assistance
Normal/
Reduced
Full or Drowsy
or Confusion
30
Totally Bed
Bound
As Above
Total Care
Reduced
Full or Drowsy
or Confusion
20
As Above
As Above
Total Care
Minimal
Sips
Full or Drowsy
or Confusion
10
As Above
As Above
Total Care
Minimal/nil
Drowsy or Coma
1
Transitional
2
E-of-life
3
4
20
Encourage patient
to see family
physician regularly
or find one.
Palliative Alerts
Establish plans
to deal with
emergencies
(e.g. pain crisis)
DNR & Advanced
directives
%
Advance care planning.
Explore pt’s
Discuss code status
understanding of illness,
Review treatment plan
discuss prognosis &
goals of care.
Ensure ESAS &
PPS/ECOG done at
Initiate
each visit.
home
care
Consult
Palliative Care
Team as
needed
Discuss
preferred
versus optimal
place of death
based on
needs &
circumstances
For some patients the decline may be more gradual
while for others it may be more precipitous
Death
ILLNESS TRAJECTORY IN PROGRESSIVE CANCER
21
Prognosticating using the PPS in Cancer
Patients
Lau F, Downing M, et al. J Pain,
PainSympt Manage. 2009;38(1)
Transitioning
End-of-life
www.advancecareplanning.ca
Cancer Care Ontario Symptom Management
Guidelines
Mobile Smartphone App & Pocket Guides:
Symptom screening
tools
https://www.cancercare.on.ca/toolbox/symptools/
3. Palliative Care Earlier Than Later
Old model of Palliative Care
Palliative Care: Earlier in illness, not only at
end-of-life
Palliative and End of Life Trajectories



29
Palliative and End of Life Trajectories



30
Palliative and End of Life Trajectories



31
4. Selecting an analgesic: The WHO Ladder
Pain: A Multidimensional construct
“I have
pain”
Total Suffering/Pain
Several domains merging
Pain
Spiritual &
existential
Other
symptoms
Total
Suffering
Psychological
Cultural
34
Social &
financial
WHO Analgesic Ladder
Selecting between different opioids
 Morphine remains first line strong opioid
 Inter-individual variability between opioids
 No large studies to demonstrate that one opioid is
superior to another
 Less constipation with fentanyl
– Clinical significance?
 Renal impairment
– May still use morphine but reduce dose/prolong dosing
intervals & monitor
– Fentanyl & buprenorphine
– Beware of methadone
Opioid Formulations
Short-acting
formulations
for
 Opioid-naïve
patients
 Pain crises
37
Long-acting
formulations
 Reserve for stable
situations
 Add short-acting
opioids for
breakthrough pain
Opioid Neurotoxicity
 Clinical Presentation
– Myoclonus, hallucinations, cognitive impairment, delirium,
severe somnolence, dysesthesia, allodynia
 Mechanism unclear
 Management strategies
– Switching opioid (opioid rotation)
– Decreasing opioid dose (if pain is well controlled)
– Hydration
38
Adjuvants for neuropathic pain
 1st line
–
–
–
–
–
TCA, gabapentin, pregabalin
Start low & go slow
Trial of at least 5-7 days before increasing dose
Monitor for side effects
NNT=3-4
 2nd line
– Pregabalin, corticosteroids
 3rd line
– Ketamine, lidocaine
Adjuvants for Bone Pain
 NSAIDs
– Limited use in severe pain
– Renal and gastro-intestinal side effects
– Limitations of Cox-2 specific NSAIDs recently noted
 Steroids
– Useful in pain crises
 Radiotherapy
– 75% to 85% response rate (decreased pain)
– Few side effects with palliative therapy
– Response within 1 to 2 weeks (maximum response up to 4
weeks later)
– Duration of analgesia is several months
40
Adjuvants for Bone Pain
 Bisphosphonates
– Reduction of skeletal events (good evidence)
– Management of more acute pain with parenteral infusion
(some controversy)
 Calcitonin
– Not effective
41
5. Managing Breakthrough Pain
Breakthrough Pain (BTP)



Transient exacerbation of pain on a
background of well controlled baseline
pain.
Variable in intensity, duration,
frequency & cause
Types
– Unpredictable
– Predictable
•

Incident Pain
“End-of-Dose” failure not BTP
•
Treatment
– Use a short acting opioid
formulation
– Use same opioid as background
treatment if possible
– Exceptions: Fentanyl
patch
– 10% of total daily dose
– Then titrate breakthrough dose
(5% to 20%)
Breakthrough pain
 Breakthrough dose needs titration (5-20%) once
baseline pain controlled
 Role of new sublingual formulations of fentanyl very
limited
– Expensive
– Patient must be on at least 60mg of oral morphine per
day
– Limited role
6. Management of Dyspnea
Is this patient short of breath?
46
47
Management Approach to Dyspnea
Screen
Assess
Identify and treat
underlying causes
if possible and
if appropriate
48
+
Treatment
of symptom
+
Communicate:
Explain situation
to patient and family
and reassure
Pharmacological Measures
to Control Dyspnea?



49
Pharmacological Measures
to Control Dyspnea
 Oxygen
 Opioids
 Adjuvant therapies
50
Non-Pharmacological Management
 Use a fan
 Position: lean forward, head up
 Avoid exacerbating activities
51
7. Management of Nausea
Brain cortex(rare)
Transmitter: GABA, Ach
Causes: Anxiety,
anticipatory nausea
Anti-emetic: Anxiolytic
Vomiting Centre
Transmitter: Ach, Dop
Causes: co-ordinates
vomiting reflex
Nausea & Vomiting: mechanisms
Chemoreceptor Trigger Zone
Neuro-transmitter: Dopamine, 5HT3
Causes
Drugs (chemotherapy, opioids, SSRIs)
Toxins (infections, cytokines)
Biochemical (hypercalcemia, uremia)
Anti-emetic:
1st line: Metoclopramide, domperidone
2nd line: Haloperidol (small dose)
3rd line: ondansetron
Anti-emetic: Same as
CTZ
Gastro-intestinal tract
Vestibular apparatus (rare)
Neuro-transmitter: Histamine
Causes: Motion sickness
Anti-emetic: Antihistamine
53
Neuro-transmitter: Dopamine, 5HT3
Causes: Tumors & tumor bulk,
Obstruction, ileus, constipation
Anti-emetic: Same as CTZ
Selecting an anti-emetic
 Depends on underlying mechanism
 1st line agents:
– Usual (one of the following)
• Metoclopramide 10mg PO QID PO/Subcut
• Domperidone 10mg TID PO (max dose 30mg/day)
– In case of bowel obstruction (one of the following)
• Haloperidol 0.5-1mg subcut BID
• Dimenhydrinate
 2nd line agents:
•
•
•
•
Dexamethasone
Ondansetron
Methotrimeprazine
Cannibinioids
 If antidopamine agent: monitor for EPS & akitisea
8. The Management of Delirium in patients
with advanced cancer
CLINICAL PRESENTATION
Clinical Subtypes
 Delirium presents in one of three forms.
Hyperactive form
Mixed form
Hypoactive form
Meagher D. Motor subtypes of delirium: Past, present and future. Int Rev Psychiatry
2009;21:59-73;
Lawlor P et al. Occurrence, causes and outcomes of delirium in advanced cancer patients: a
prospective study. Archives of Internal Medicine. 2000;160:786-794.
CAUSES OF DELIRIUM
Causes per episode
 Often multifactorial etiology per episode
– On average, 3 causes per episode
• E.g. opioid neurotoxicity, dehydration and hypercalcemia




Consider several causes concurrently
Sometimes the causes are unclear or cannot be found
Urinary retention aggravates delirium
Consider underlying dementias in very elderly patients
Lawlor P, et al. Occurrence, causes and outcomes of delirium in advanced cancer
patients. Archives of Internal Medicine. 2000;160:786-794.
Bruera E et al. Impact of delirium and recall on the level of distress in patients with
advanced cancer and their family caregivers. Cancer 2009;115:2004-2012
57
Common Causes of Delirium in Palliative Care

Drugs
–
–
–
–



Opioids
Anticholinergic drugs such as tricyclic antidepressants
Anticonvulsants
Benzodiazepines
Infections
Dehydration
Metabolic/Organ failure
– Renal or liver failure, hypercalcemia, hyponatremia




58
Hypoxemia
Brain disease: metastases or primary brain tumors
BZP withdrawals (uncommon)
Full bladder (aggravates)
Overall management approach
Role of benzodiazepines in Palliative Care
Benzodiazepines
 Appear to worsen
delirium in palliative
patients.
 Generally avoided.
Breitbart W et al. Doubleblind trial of haloperidol vs
chlorpromzine vs
lorazepam in palliative
AIDS pts. J Am Psych
1996;153(2):231-237
DELIRIUM Management Guidelines. Cancer
Care Ontario 2010
Pharmacological management
Symptom Management- 1st line
Mild
Haloperidol 0.5mg or
1mg po or subcut OD or
BID
PLUS
Haloperidol 0.5mg or 1mg
PO /subcut q1hr PRN
Then titrate dose if initial
dose ineffective
(see “moderate” doses)
Moderate
Haloperidol 2mg or
2.5mg po or subcut BID
to TID
PLUS
Haloperidol 2mg PO
/subcut q1hr PRN
OR
Methotrimeprazine
Then titrate dose if initial
dose ineffective
Severe
Single dose of midazolam
2.5mg to 5mg subcut stat
PLUS
Haloperidol 5mg subcut
stat
OR
Methotrimeprazine
Follow with haloperidol
2.5mg or 5mg q 30min
PRN subcut
(max of 10-15mg /day)
The Role of the Atypical versus Traditional
Antipsychotic medications
 Haloperidol remains 1st line
 Methotrimeprazine 2nd line
 Newer atypical antipsychotics reserved for:
– Pts requiring longer term treatment
– Pts with EPS on haloperidol
– Olanzapine can be given SC
The Myth of the “PLEASANT CONFUSION”
 54% of pts whose delirium resolved recalled the
delirium experience.
 78%: delirium as highly distressing
 Patients with hypoactive delirium were just as
prone to experiencing distressing delirium as those
with hyperactive delirium.
Breitbart W et al. The Delirium experience:
Psychosomatics. 2002;43:183-194
9. Depression at the End of Life
Diagnosing depression in palliative care context
 What is the prevalence of a major depression in
patients with advanced disease?
Diagnosing depression in palliative care context
 What is the prevalence of a major depression in
patients with advanced disease?
– 10-15%
– 25% in pancreas cancer
 Challenge
– Somatic symptoms non-specific
• Weight loss, fatigue
 Pervasice Worthlessness, guilt, hopelessness,
death wish
Management
 Supportive Counseling in all
 Pharmacological management in some (where
ability function is affected)
–
–
–
–
–
Citalopram (sedating)
Venlafaxine (stimulating)
Mirtazapine (sedating, appetite stimulation)
Duloxetine (if requires adjuvant analgesic)
Methylphenidate (short onset of action)
10. Airway secretions
Airway “rattle” at end of life
 Differentiate between upper and lower airway
secretions.
 Upper airway secretions:
– If mild to moderate:
• Reposition & reassure family
– If severe
• Reposition, reassure, anticholinergic
Glycopyrrolate 0.4mg Subcut q2 hrs prn
OR Scopolamine 0.4mg Subcut q 4 hrs prn
 Lower airway secretions (Pulmonary edema)
– Furosemide 20mg-40mg subcut stat
End of Life “Comfort measures” (last hrs/days)
 Avoid blanket orders
 No need to start “morphine drip” if there was no
pain before
 No need to start midazolam drip if there is no
refractory symptom and palliative sedation is not
required
QUESTIONS??