Cancer Pain Management

Amal Khalifa
Professor of Clinical Oncology
Breast Division - University of Dammam
Significance of Severe Pain

“Worse than torture”

 Outcome of Cancer Treatment

Curative Treatment 30% Cure

45%

Diagnosis
15%
of Cancer

55%
Terminal
Palliative Treatment 70% Care
ECOG Study of 15 Cancer Centers 1998

– 61% percent of the sample had pain

– 40% of those with pain rated it as significant

(i.e., greater than 5 on a 0 to 10 scale)

– No patient in this sample was reported to be

receiving morphine or a morphine-like opioid
 ECOG Study of 15 Cancer Centers
• Most common reason to seek medical attention

• 60-90% with advanced cancer have pain

• 50 to 75% report inadequately relieved pain

• 25 % die with unrelieved excruciating pain

• 80-90% can be managed relatively simple with oral analgesics

 Indifference to Pain

• Only a few healthcare professionals will

ever experience and understand chronic
excruciating pain
• D. Dumlao
Why?
 Barriers to Effective Pain Management

• Patients and carers

– reluctant to complain about symptoms
– fear pain and don’t know how to get help
– lack knowledge about strong opioid analgesia
– fear adverse effects leading to poor adherence.

• Healthcare professionals
– fail to assess pain adequately
– reluctant to prescribe and monitor effective analgesia
– provide insufficient education to promote self-management

• Healthcare systems
– fail to recognise patients with cancer pain
– communicate data on pain ineffectively
– prevent patients receiving timely analgesia
Risk of Addiction and Substance Use Disorders
among Patients Receiving Opioid Medications

• Actual risk is low

• The risk is over estimated
• Physical dependence is not addiction
• These concerns results in physician reluctance
to write opioids and patient reluctance to use
them
Barriers involving healthcare systems have
been reduced since the standards of the
JCAHO 1998---Which asserts that pain
management is a patient right

• However, barriers, such as failure to

adhere to standards and guidelines,
still exist
 Goal of Pain Management
Titrate dose until adequate pain control is achieved
or Intolerable adverse / toxic effects manifest

Determine the dose that will control excruciating pain

The best pain medication is the drug that will control pain
without adverse effects
The Concept of Total Pain

Spiritu Psycho
al logical

Social
Total
Pain

Physic
al
 Physical pain
• Other symptoms
• Adverse treatment effects

Depression Anger
•Loss of social position
•Bureaucratic bunging
•Loss of job
•Delays in diagnosis
•Loss of role in family
•Unavailable physicians
•Chronic fatigue &insomnia
Total •Uncommunicative physician
•Sense of helplessness
•Disfigurement pain •Failure of therapy
•Friends who do not visit

Anxiety
•Fears of hospitals
•Fear of pain
•Fear of death
•Worry about family& finances
•Spiritual unrest, uncertainty about future
 Clinical Guideline For Patient Assessment
Medical Assessment

Physiotherapy Psychological
Assessment Assessment
Group Meeting with
Patient

Treatment Pathway

Review Meeting with Patient

 Assessment of Pain
1- The initial evaluation.
2- The "ABCDE":
* Ask about the pain regularly.
* Assess pain systematically.
* Believe the patient and family.
* Choose appropriate pain control options
* Deliver interventions in a logical fashion.
* Enable patients to control their life.
(The Agency for Health Care Policy and Research)
Assessment of Pain
 Issue No. 1 - January 2007
23-28
Evaluation of the prevalence, pattern and management of cancer
pain in Oncology Department, The Royal Hospital, Oman
M. Faris, B. Al- Bahrani, A. Emam Khalifa, N. Ahmad
Oncology Department , The Royal Hospital, Muscat

Introduction: Pain is under-treated in all parts of the world. Moderate to severe pain is
experienced by the majority of patients with advanced disease. The aim of this study is to
evaluate the prevalence, pattern and pain management in Oman. Methods: A prospective
study was carried out during a 3 months period. We evaluated all admitted patients and
only patients who were complaining of pain were eligible. Assessment of pain intensity
and pain relief were done using measuring scales. All patients received pharmacological
treatment according to WHO analgesic ladder. Results: A total of 335 admissions were
recorded during the study period of which 100 patients (30%) were eligible for the study,
52% of cases were males. The mean age was 45 years ± 16.2 years and the most common
tumors were GIT and breast cancer. Sixty four patients had pain but did not complain
about it. Forty-five patients (45%) had moderate pain but they did not routinely complain
about it. The mean hospital stay was 3.5 days and the range 1- 10 days. Conclusions: Most
cancer patients deny pain for various reasons. Thorough history and repeated pain
assessment are very important. Following the WHO analgesic ladder is simple and
effective.
2012
2014
Management of Cancer Pain
 World Health Organization
(WHO) Step Ladder Approach

Severe Pain 7-10/10

Moderate Pain 4-6/10 Potent opioids (e.g.

morphine) +/-
non-opioids
Weak opioids +/- non-
Mild Pain 1-3/10
opioids (e.g. Tylenol #3®)
ASA, Tylenol,
NSAIDS
 Adjuvants to Opioid Therapy
Adjuvant Common indication
Alpha agonists Neuropathic pain
Anticonvulsants Neuropathic pain
Antihistamines Nausea, pruritus
Benzodiazepines Pain w/Anxiety
Bisphosphanates Bone pain (cancer)
Corticosteroids Bone pain (cancer)
NSAIDs / COX-2 I Musculoskeletal pain
Tricyclic anti-depressants Neuropathic pain
 Pharmacokinetics of Opioids

• Renal Excretion
• Metabolized in the liver
• Concern is with toxic metabolites which can cause neurotoxicity
– 6 morphine glucuronide
– Normeperdine
– Norpropoxyphene
– 6 hydromorphone
– Norfentanyl
• Onset of action ranges from 0 to 15 minutes (IV) or 15 to 30
minutes (po) (depends on lipid solubility)
• Duration of action
 Pharmacokinetics of Commonly Used Opioids

• Dilaudid (Hydromorphone):
– Half life: 1 to 3 hours
• Morphine:
– Duration of analgesia: 2 to 6 hours
– Half life: 2 to 4 hours
•  Fentanyl:
– Duration of analgesia: 0.5 – 1 hour
– I.V half life: 2 - 4 hours
– Transdermal patch half life: 17 hours (13-22 hours, half-life is influenced by absorption
rate)
– Transmucosal half life: Lozenge: 7 hours
– Buccal film: 14 hours
– Buccal tablet half life: 100-200 mcg: 3-4 hours, 400-800 mcg: 11-12 hours
• Methadone
– Duration of analgesia: Oral: 4-8 hours, increases to 22-48 hours with repeated doses
– Half-life elimination: 8-150 hours
 Which Opioid Analgesic to Use?

• Pharmacokinetics
• Patient co-morbidities ( Kidney and liver Disease:
Methadone or Fentanyl)
• Intensity of pain
• Previous experience with opioid analgesics
– Considerable inter-individual variability in response to each opioid
– Adverse events
– True allergy to opioids (Drugs of choice: Methadone or Fentanyl)
• Etiology of pain
– Nociceptive
– Neuropathic
– Opioid Induced Hyperalgesia
• Total daily dose of pain medications
 Morphine
 There is no standard dose of morphine for
the treatment of cancer related pain
 The correct dose of morphine is that which
controls the pain with tolerable side effect
 The dose must be individualizes
 Morphine should be given with caution to
patients with:
– Renal impairment
– Severe hepatic dysfunction
– CNS depression from any cause
 Administration of Morphine

 Oral morphine is the preparation of

choice for patients with moderate or
severe pain who are able to take oral
medications.
 Oral morphine mixture (Short acting)
– Morphine mixture is commercially available in
2mg/ml, 5mg/ml, 10mg/ml strengths
– Cheap, well absorbed, well tolerated
– Effective in 85% of patients
– Easy to take (30-100ml/24h)
• Initial dose
– Patients on Tramal, 20% of total dose/day
– Patients receiving oxycodone, same dose (mg/d)
– Patients not previously receiving opioids, start with
10mg PO q4h, if frail, elderly or with renal
impairment, start 5mg PO q4h.
• Frequency
– 4-hourly, 2 am dose should be given unless patient
sleeps through and does not wake with pain which
is difficult to control. May be avoided by giving
increased dose at 10pm.
– Breakthrough pain is treated with an extra dose, as
often as required. The dose is the same as the 4-
hourly dose.
 What Dose to Give an Opioid Naïve Patient?

• For opioid naïve start at a morphine equivalent of 2 to

5 mg IV or 10 mg PO

• Dose escalation should be more than 30 to 50% of base

dose to observe a meaningful change

• Frequency of parenteral dosing can be as often as

every 15 to 30 minutes until adequate analgesia is
achieved
 Opioid Analgesic Usual Starting Dose
Drug Equianalgesic Starting iv iv:po ratio Starting dose Duration of
parenteral dose po /transdermal Action
dose
Morphine 10 mg Bolus 1:3 0.15-0.3 3-4 hours
dose=0.05-0.1 mg/kg/dose
mg q 2-4
hours q 4 hours
Continuous
infusion=0.01-
0.04 mg/kg/hr

Hydromorphone 1.5 mg 0.015-0.02 1:5 0.06 mg/kg 2-4 hours

mg/kg q 4 q 3 to 4 hours

Oxycodone 5-10 mg N/A 0.1-0.2 mg/kg q 3 3-4 hours

to 4

Fentanyl 100mcg 1 to 2 25 mcg patch 72 hours

mcg/kg/hr as
continuous
infusion
Methadone 10 mg 0.1 mg/kg q 4 1:2 0.2 mg/kg 12 to 150
to 8 hours q 4 to 8 hours hours
 Once Analgesia is Achieved
• A regular dosing schedule of every four hours
can be started
• Rescue or breakthrough dosing
– 30% to 50% of every 4 hour dosing
– 10 to 15 percent of total 24 hour dose
– Best time to give rescue dose is time of peak onset
• Convert to PO or transdermal if possible
 Breakthrough Pain
• Patients on long-acting med always need second, short-
acting med, for breakthrough pain to take Q 4 hours or
less.
• Generally, dose of breakthrough opioid should be:
– 10% of 24 hour dose of analgesics and made available
Q 2-4 hours.
– Example: MS Contin 60mg q12hrs breakthrough dose
should be immediate release morphine (MSIR), 10-15
mg Q 2-4 hrs prn.
 Shifting from one opioid to another
(Incomplete cross-tolerance)
• If switching from one opioid to another, recommended
to start the new opioid at ~50% of equi-analgesic dose.
• Why? :Because the tolerance a patient has towards one
opioid, may not completely transfer (“incomplete cross-
tolerance”) to the new opioid.

to
from
100% 50%
of new Opioid
Fentanyl
 Conversion Table for Fentanyl
Morphine PO 3
1

Dilaudid IV 1 1
5 20
Dilaudid PO 1 1 5
2 8 1
Methadone PO 1 1 2
2 6 1
Oxycodone PO 1.5 1 10 4 3
1 2 1 1 1
Morphine IV Morphine PO Dilaudid IV Dilaudid PO Methadone PO

10 mcg IV 25 mcg TD IV Fentanyl 1:4 200 mcg Actiq = Morphine to 1mg IV methadone
Fentanyl =1 mg IV Fentanyl/HR = 45 TD Fentanyl 10 mg oxycodone Methadone ratio = 2 mg PO
morphine mg PO Morphine 30 to 90 mg morphine methadone
= 4:1
91 to 300 mg = 8:1
>300 mg =12:1
Patient –Controlled Analgesia
 Disadvantages of Dosing with PCA

• May increase adverse effects like

– Sedation
– Nausea
– Respiratory depression
Clinical Questions
 Clinical Question #1
A 40 yr. old women with stage IV ovarian cancer reports
mild to moderate burning pain in her hands and feet.
Ibuprofen has not been effective. You suggest:

a. A COX-2 inhibitor
b. Topical capsaicin
c. A steroid
d. An adjuvant with activity in neuropathic pain
 Answer #1
d. An Adjuvant with activity in neuropathic
pain
• Pain characterized by sharp, shooting, electric
shocks, parethesias, dysesthesias, cold
extremities
• Neuropathic pain often responds poorly to
NSAIDs and opioids
 Clinical Question #2
A 63 yr. old man with advanced prostate cancer has been
stable on oral morphine 30 mg every 4 hours. He is now
NPO and you are going to switch him to IV morphine. The
correct IV dose is:

a. 4 mg IV q 4 hours
b. 6 mg IV q 4 hours
c. 10 mg IV q 4 hours
d. 30 mg IV q 4 hours
 Answer #2
c. 10 mg IV q 4 hours
ORAL MED PAREN-
DOSE TERAL
(MG) DOSE
Rationale: (MG)

• Equianalgesic ratio for 30 Morphine 10

morphine is 7.5 Hydro- 1.5

morphone
1 mg IV = 3 mg PO.
(Dilaudid
• When writing start time for ®)

the first dose, consider time 20 Oxycodone --

of last oral dose.

30 Hydro- --
codone
 Clinical Question #3
A 69 yr. old patient with metastatic prostate cancer to the
lumbar spine is taking OxyContin® (sustained release
oxycodone) 100 mg every 8 hours. What should be the
opioid for his breakthrough pain and at what dose and
interval?

a. Oxycodone 30 mg PO every 4 hours

b. Oxycodone 30 mg PO every 8 hours
c. Morphine 10 mg PO every 4 hours
d. Morphine 10 mg IV every 8 hours
 Answer #3
a. Oxyocodone 30 mg PO every 4 hours

Rationale:
• In general, keep PRN, short acting opioid the same drug as the
long-acting opioid.
• Starting dose for breakthrough pain is 10% of the total daily dose
(and you can always titrate).
• Here total daily dose = 300 mg, so 10% of this = 30 mg. The PRN
interval should never be longer than the expected analgesic
duration (~4 hours in this case), and can often be less.
 Clinical Question #4
A 45 yr. old woman with colon cancer metastatic to the liver, had
been admitted for uncontrolled pain. Her pain is now controlled
and stable on PCA morphine of 10 mg/hr. The boluses are 5 mg
q15 minutes PRN and work very well but she rarely needs to use
the bolus doses for breakthrough pain. She is to be discharged
home on oral opioids. What opioid/formulation and what dose
would you recommend?

a. MS Contin 120 mg PO Q 12 hours

b. MS Contin 240 mg PO Q 12 hours
c. MS Contin 360 mg PO Q 12 hours
d. Fentanyl patch 50 mcg Q 72 hours
e. Dilaudid 8 mg PO Q 8 hours
 Answer #4
c. MS Contin 360 mg PO every 12 hours
Rationale:
• Patient already on morphine, so use same opioid.
• Using long-acting formulation is the oral equivalent
of a continuous infusion.
• Total daily dose of morphine IV is 240 mg and the
oral equivalent is 720 mg of morphine, can be given
as 360 mg of MS Contin PO every 12 hours.
 Equianalgesic Doses: Opioid Analgesics

ORAL DOSE ANALGESIC PARENTERAL

(MG) DOSE (MG)

30 Morphine 10

7.5 Hydromorphone 1.5

(Dilaudid ®)

20 Oxycodone --

30 Hydrocodone --
 Clinical Question #5
What breakthrough pain opioid/formulation would you recommend
for the same patient if she takes MS Contin 360 Mg Q 12 hours?

a. Morphine elixir 20 mg PO every 2-4 hours PRN

b. Morphine immediate release tablets 40 mg PO Q 2-4 hours

PRN

c. Morphine immediate release tablets 60 mg PO Q 2-4 hours PRN

d. Morphine immediate release tablets 70 mg PO Q 2-4 hours PRN

 Answer #5
d. Morphine immediate release tablets 70 mg PO every 2-4 hours PRN.

Rationale:
• Breakthrough pain requires a short-acting formulation.
• Preferable to use same opioid as long-acting.
• PRN initially 10% of the total daily dose = 10% of 720mg = 72mg.
• Dosing interval is q2-3h PRN. We don’t expect that pts will need to
take 12 doses in 24hr (our pain regimen would be really off).
• If patient requires >5 PRN doses/day, either the PRN dose needs
adjusting or the basal dose or both.
The under-treatment of pain is still a
major issue in both oncology and
palliative medicine

“Freedom from pain should

be seen as a right for every
cancer patient”
THANK YOU