Pain and Symptom

management in cancer
patients
Ann Huot M.D. M.Sc. CFPC
Cross Cancer Institute
April 16th, 2016

Faculty/Presenter Disclosure
Presenter: Dr. Ann Huot
Relationships with commercial interests:

Grants/Research Support: Non Applicable

Speakers Bureau/Honoraria: Non Applicable
Consulting Fees: Non Applicable
Other: Non Applicable

Disclosure of Commercial
Support
This Program is funded through AHS
Operational Funding.
Potential for conflict(s) of interest: None
Dr. Ann Huot is presenting at this Program on
a voluntary basis

Objectives
List key elements of cancer pain
assessment.
Select appropriate non-opioid, opioid and
adjuvant analgesics.
Become familiar with common causes
and management of nausea/vomiting
and constipation.
Know the main anxiolytics used with
palliative care patients.

Cancer pain assessment

Comprehensive assessment is key to
management
Etiology
Pathophysiology
Severity
Aggravating/alleviating factors
Other symptoms
Prognostic factors

Etiology

Related to cancer
Related to cancer treatment
Unrelated to cancer

Pathophysiology
Type

Localization

Quality

NOCICEPTIVE
Bone/soft tissue
Visceral

Well-localized
Poorly-localized

Achy, sharp, mvt related

Achy, sharp,crampy

NEUROPATHIC
Spine, brachial plexus
involvement

Dermatome

burning
tingling
pins and needles
numbness

Severity

Scales
Numerical: 0 to 10
Verbal: none, mild, moderate, severe
Impact on function
Activities
Sleep

Aggravating/alleviating
factors
Physical
Psychological
Previous interventions for pain:
analgesic and adverse effects

Relevant past history

CAGE score
Drugs abuse
Previous history of chronic pain, depression,
anxiety, PTSD, significant losses.

Poor prognostic factors

Edmonton Classification System for Cancer Pain

1. Mechanism of pain
No
Nc
Ne
Nx

No pain
Nociceptive
Neuropathic
Unknown

2. Incident pain

4. Addictive behaviour
Ao Absent
Aa Present
Ax Unknown

5. Cognitive function
Co
Ci
Cu
Cx

Io Absent
Ii Present
Ix Unknown

No impairment
Partial impairment
Total impairment
Unknown

3. Psychological distress
Po Absent
Pp Present
Px Unknown

Nekolaichuk CL et al. Palliat Med 2005; 19:466-76

Fainsinger RL et al. J Pain Symptom Manage 2005;
29:224-37

This image cannot currently be displayed.

Other
symptoms
Edmonton
Symptom
Assessment
System revised
(ESAS-r)

Watanabe SM et al.
J Pain Symptom Manage
2011; 41:456-468

Selecting an analgesic:
the WHO ladder

Step 1 non-opioid analgesics:

Acetaminophen, NSAIDs
Acetaminophen
Maximum 4 g/day
NSAIDs
Not to be used in frail elderly patients
Prescribe PPI and monitor renal function

McNicol E et al. Cochrane Database of Systematic Reviews 2005

Step 2 Opioids:
Codeine

Metabolized to morphine by CYP2D6 and

CYP3A4 into inactive metabolite 5%-10% of
Caucasians lack activity so difficulty to reach
good pain control/increased risk of toxicity
Triplicate not required
Gastric effect
?Advantage vs. low-dose morphine

Step 2 Opioids:
Tramadol
Mild opioid effect plus noradrenergic/
serotoninergic reuptake inhibition
Available as sustained-release, or immediaterelease in combination with acetaminophen
Systematic review: not proven to be superior to
codeine
Careful with anti-depressants
Triplicate not required
Not on AHW Drug Benefit List
Tassinari D et al. Palliat Med 2011; 25:410423

Step 3 Opioids: Morphine,

hydromorphone, oxycodone
All are acceptable first-line opioids
Excreted in the kidneys
Note that injectable oxycodone is not
available commercially; can be reconstituted
from powder

Wiffen PJ et al. Cochrane Database of Systematic Reviews 2007

Step 3 Opioids: Fentanyl

Transdermal
72 hour release not suitable for rapid titration
Indication: stable pain
Systematic review: less constipating than oral
morphine; low level of evidence to justify
widespread use
No active metabolites may be used in renal
failure and potentially causing less toxicity

Tassinari D et al. Palliat Med 2011; 25:478487

Step 3 Opioids: Methadone

Pros
NMDA receptor antagonist
Lack of active metabolites
Not dependent on renal clearance
Cons
Long, unpredictable half-life (24-36h)
Drug-drug interactions
Association with QT prolongation, TdP
Requires special prescribing authorization
Systematic review: not proven to be superior to other
opioids
Nicholson AB. Cochrane Database of Systematic Reviews 2007

Initiating Opioids
Morphine 2.5-5 mg PO q4h
Oxycodone 2.5- 5 mg PO q4h
Hydromorpone 1 mg PO q4h
Fentanyl patch 12-25 mcg/h
Add breakthrough dose:
regular dose or 10% daily dose
Q1-2h

Opioid side effects

Somnolence
Nausea
Constipation
Respiratory depression

Severe somnolence
Vivid dreams, nightmares
Hallucinations
Myoclonus
Hyperalgesia/allodynia
Delirium
Generalized seizures

Note that true opioid allergies are rare

Opioid rotation
For signs of opioid toxicity
Lack of pain control despite appropriate dose
titration
Impractical dose
Consider rotating within 1st line opioids and
monitor closely
Calculate total dose over 24h and add 2-3 BTA
if consistently using.
Usual conversion with 30-50% reduction

Opioid Dose Conversion Ratios

Codeine 100 mg PO (-10x)

Morphine 10 mg PO
Oxycodone 7.5 mg PO (+1.5x)
Hydromorphone 2 mg PO (+5X)
Methadone 1 mg PO (+10x)

CASE
Mrs. S is on Morphine 100 mg po q4h and 50 mg po q1h
prn for severe diffuse bony pain. She uses 8 BTAs per
24h. She shows progressive signs of drowsiness, vivid
dreams and myoclonus.

100 x 6= 600
50 x 3 BTA= 150
600+150= 750 mg total Morphine
750 divided by 5= 150 mg HM/30%= 100 mg HM
HM divided by 6= 16 mg
HM 16 mg (2x 8mg tab)po q4h and 8 mg po q1h prn.

Transdermal buprenorphine
(Butrans)
Partial agonist
Low-dose 7 days patch (5, 10, 20 mcg/h)
appropriate for moderate stable pain (chronic)
Not dependent on renal clearance
?Less addictive potential, constipation
Systematic review: very low level of evidence
Not on AHW Drug Benefit List

Tassinari D et al. Palliat Med 2011; 25:478487

Oxycodone-naloxone (Targin)
Sustained-release Oxycodone plus opioid
agonist Naloxone in 2:1 ratio
Single RCT of OXN vs. OX (maximum dose 120
mg/day) in 185 cancer patients
OXN less constipation, no difference in pain
Available in 10, 20, 40 mg (Oxy) q 12h.
Not on AHW Drug Benefit List

Ahmedzai SH et al. Palliat Med 2011; 26:50-60

Abstral Transmucosal Fentanyl

Used for breakthrough analgesia

Opioid tolerant: oral morphine equivalent 60
mg/day for 1 week
Start at lowest dose (100 mcg) and titrate up
(max 800 mcg)
Doses at least 2 hours apart; maximum 4
doses/day
Not on AHW Drug Benefit List
Abstral Product Monograph 2011

Adjuvant analgesics for

neuropathic pain
Anticonvulsants
Gabapentin: drug of choice; well-tolerated; evaluated in
cancer pain; slow to titrate (max. dose 3600 mg/d)
Pregabalin: equivalent efficacy, tolerability; faster to
titrate; 300 mg BID (not on AHW Drug Benefit List)
Antidepressants:
TCAs (Nortriptyline, Desipramine)
SSNRIs (Venlafaxine, Duloxetine): better tolerated
Mirtazapine (not confirmed in RCTs)
Topical lidocaine (for localized pain)
OConnor AB, Dworkin RH. Am J Med 2009; 122:S22-S32
Howard, J Pain Sympt.Mgmt 2012; 44:763-783
Lavoie Smith and al JAMA 2013; 309, 13: 1359-67.

Adjuvant analgesics
for bone pain
Bisphosphonates
Clodronate, Pamidronate, Zoledronic acid
Systematic review: modest pain relief for patients with
painful bone metastases (multiple myeloma, breast and
prostate cancer)
Contra-indicated in renal impairment

Calcitonin
Systematic review: does not support use for bone pain
Wong RKS, Wiffen PJ. Cochrane Database of Systematic Reviews 2002
Martinez-Zapata MJ. Cochrane Database of Systematic Reviews 2006

Corticosteroids
Anti-inflammatory, anti-edema effects
Used for bone, visceral, neuropathic pain
Limited evidence
Short-term measure (significant adverse effects
with long-term use)
Do not use with NSAID
Usual dose Dexamethasone 4-8 mg po at 8 am
and noon x 1-2 weeks / then taper
Reduction of cancer-related fatigue

Key message

Comprehensive assessment is the foundation of

pain management
Judicious selection of non-opioid, opioid and
adjuvant analgesics can provide satisfactory pain
control in the majority of cases

Frequent Gastro-intestinal
Symptoms

Nausea and Vomiting

Cause is often multi-factorial:
Constipation
Drugs

Opioids
Selective serotonin reuptake inhibitors
Non-steroidal anti-inflammatories (NSAIDs)

Reduced gastro-intestinal motility

Drugs (opioids, tricyclic antidepressants)

Autonomic neuropathy

Metastatic bowel disease / obstruction

33

Nausea and Vomiting

(continued)

Anorexia-cachexia syndrome
Metabolic causes:
Hyper Ca++
Uremia
Hypo Na+

Increased intracranial pressure

Thrush
Anxiety
May be aggravated by uncontrolled pain
34

Nausea & Vomiting: mechanisms

Brain cortex
GABA
Anxiety, anticipatory nausea

Vestibular app.
Histamine
Motion induced

Vomiting
Centre
ACH, dopamine

Gastro-intestinal tract
dopamine, 5HT3
Tumors
Obstruction
Distension

Chemoreceptor trigger zone

dopamine, 5HT3
Drugs (e.g. chemotherapy, opioids,
SSRIs)
Toxins (infections, etc)
Biochemical (e.g. hypercalcemia,
uremia, etc)

35

Management
Attempt to correct the underlying cause(s)
Treat the symptoms
Anti-emetics selected according to the inferred underlying
mechanisms

Prevent nausea
Employ a regular anti-emetic regimen if nausea is prolonged
Prevent constipation

If one agent not completely effective, review and add

another or replace with another
36

Anti-Emetics
Anti-dopamine agents

Metoclopramide
Domperidone
Haloperidol
Olanzapine

Anticholinergic

5HT3 antagonists
Ondansetron
Granisetron

Antihistamines
Dimenhydrinate

Hyoscine hydrobromide
(Scopolamine)
Antidopaminergic agents
plus anticholinergic effects
Methotrimeprazine
Prochlorperazine
37

Anti-Emetics
Pro-motility and anti-dopamine agents
Metoclopramide 10-20 mg QID po/sc/pr
Extrapyramidal side effects may occur
Upper GI pro-motility

Domperidone 10-20 mg QID po

Only oral formulation
Less likely to cause extrapyramidal side effects
Upper GI pro-motility

Extrapyramidal side effects and akathisia are

relatively uncommon, but monitor for these.
38

Anti-Emetics
Anti-dopamine agents

Haloperidol 0.5 - 2 mg po/sc od-qid

Olanzapine 2.5 - 10 mg od-bid
Methotrimeprazine 2.5 - 10 mg po/sc od-tid
Useful in the context of malignant bowel obstruction

Steroids
Dexamethasone 4-8 mg po/sc, od-bid

Dimenhydrinate
Best for motion-related nausea (seldom)
May be used in bowel obstruction

5 HT3 antagonists
First line for chemo-induced nausea
Useful second and third line agents

39

Role of Cannabinoids

Role in Chemotherapy and Radiotherapy

induced nausea
Stimulates Appetite
Decreases anxiety and improves sleep
Associated with more sedation, dizziness

Constipation

Very common
Often missed
Needs to be prevented
Common cause of nausea and abdominal discomfort
Can present as diarrhea, fecal incontinence

42

Assessment
Review fluid intake
Diet including fibers, bananas
Prolonged immobility
Medications (anti-cholinergic, 5HT3 antagonist
anti-emetics, antacids, opioids)
Metabolic (hyperCa, hypoK)

Abdominal XR (CS 10/12)

Management
Constipation prevention
17 g po daily to BID
Moderate constipation (C.S. 7-9/12)
PEG 17 g po BID to TID
Sennokot 8.6 mg 2 tabs po BID prn
Severe constipation (C.S.10-12/12)

Mineral oil + soap suds enema

Followed by PEG 17 g 2-3x/day

REFRACTORY OPIOID-INDUCED
CONSTIPATION
Methylnaltrexone (Relistor)
1.5 mg/kg sc (max 3 doses)

Naloxegol (Movantik)
25 mg po daily
Costs $6 per tablet
70% patients respond within 24h

Key Message
A variety of anti-emetics are available
therefore our patients should not suffer from
nausea.
Constipation can be a distressing side effect for
patients on opioids so laxatives should always
be prescribed.

ANXIETY/DEPRESSION

Common anxiolytic medications

Benzodiazepines
Olanzapine (zyprexa)
Mirtazapine (remeron)
Duloxetine (cymbalta)
Venlafaxine (effexor)
Pregabalin (lyrica)
Quetiapine (seroquel)
Risperidone (risperdal)

Benzodiazepines
Habit forming
CNS side-effects
Withdrawal effect/rebound

Short-term
Treatment in crises (less than one month)
Lorazepam
clonazepam

Olanzapine

Atypical anti-psychotic
Contraindicated in cerebrovascular disease; may increase
risk of stroke in elderly pts
Main side-effect: weight gain
Poorer response in pts more than 70 yo, dementia, central
nervous system spread of cancer
Initial dose 2.5 mg-5 mg po hs (up to 15-20 mg)
Oral and sublingual (sc uncomfortable)

Mirtazapine
Dual action
Action within 1-3 weeks
Main side-effects: somnolence, dizziness
Relatively contra-indicated in renal and liver
failure
Used for depression, anxiety, insomnia, antipruritic, anti-emetic, appetite stimulant,
adjuvant analgesic for neuropathic pain
Initial dose 15 mg hs up to 30-45 mg hs

Duloxetine
SNRI
Easier to titrate than Venlafaxine
1st line therapy for depression/anxiety (also
for neuropathic pain, fibromyalgia, stress
urinary incontinence)
Avoid in severe renal and hepatic failure
No CV risk
Dose range 60-120 mg/d

Venlafaxine
SSRI
Well-tolerated
Can be considered 1st line therapy for
depression/anxiety
Decreased dose by 50% in renal dysfunction
Usual dose 75-150 mg BID

Pregabalin

Indicated for anxiety, fibromyalgia, seizures,

neuropathic pain
Elimination half-life 6 hours: achieve steady
state in 24-48 hours
Main side-effects: dizziness, somnolence
Dose range 150 mg-600 mg/d

Quetiapine
Atypical anti-psychotic
Indicated for anxiety and delirium

Rapid onset of action

Risk of EPS lower than 1st generation (++)
Start at 25 mg hs
Need to use 300-400 mg for delirium (in 2-3
divided doses)

Risperidone

Atypical anti-psychotic
May increase risk of stroke in elderly patients and not
approved for dementia-related psychosis
More slowly eliminated in elderly pts or with renal
impairment
Mild delirium: 0.5-1 mg po BID
Moderate 1-3 mg po BID (max 6 mg/day)

To conclude

TRUE COMPASSION MEANS

NOT ONLY FEELING
ANOTHERS PAIN BUT ALSO
BEING MOVED TO HELP
RELIEVE IT.
Daniel Goleman

Additional Resources
Pallium Palliative Pocketbook
www.palliative.org
Ann.Huot@albertahealthservices.ca
Telehealth Virtual Pain and Symptom Clinic
Symptom Control and Palliative Care department
780-432-8350