1. Cancer Pain Management
Amal Khalifa
Professor of Clinical Oncology
Breast Division - University of Dammam

2. Significance of Severe Pain
“Worse than torture”

3. Outcome of Cancer Treatment
Curative Treatment
30%
Cure
45%
Diagnosis
of Cancer
15%
55%
Terminal
Care
Palliative Treatment
70%

4. 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

5. 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

6. Indifference to Pain
Only a few healthcare professionals will ever experience and understand chronic excruciating pain
D. Dumlao

7. Why?

8. 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

9. 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

10. Barriers involving healthcare systems have been reduced since the standards of the JCAHO Which asserts that pain management is a patient right
However, barriers, such as failure to adhere to standards and guidelines, still exist

11. 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

12. The Concept of Total Pain
Physical
Social
Spiritual
Psychological

13. Anger Total pain Physical pain Other symptoms
Adverse treatment effects
Anger
Bureaucratic bunging
Delays in diagnosis
Unavailable physicians
Uncommunicative physician
Failure of therapy
Friends who do not visit
Depression
Loss of social position
Loss of job
Loss of role in family
Chronic fatigue &insomnia
Sense of helplessness
Disfigurement
Total
pain
Anxiety
Fears of hospitals
Fear of pain
Fear of death
Worry about family& finances
Spiritual unrest, uncertainty about future

14. Clinical Guideline For Patient Assessment
Medical Assessment
Physiotherapy Assessment
Psychological Assessment
Group Meeting with Patient
Treatment Pathway
Review Meeting with Patient

15. 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)

17. Assessment of Pain

18. 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 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.

19. 2012

20. 2014

23. Management of Cancer Pain

24. World Health Organization (WHO) Step Ladder Approach
Severe Pain 7-10/10
Potent opioids (e.g.
morphine) +/-
non-opioids
Moderate Pain 4-6/10
Weak opioids +/- non-
opioids (e.g. Tylenol #3®)
Mild Pain 1-3/10
Note: Ask students to provide clinical example from the wards of each level of pain.
ASA, Tylenol,
NSAIDS

25. Adjuvants to Opioid Therapy
Common indication
Alpha agonists
Neuropathic pain
Anticonvulsants
Antihistamines
Nausea, pruritus
Benzodiazepines
Pain w/Anxiety
Bisphosphanates
Bone pain (cancer)
Corticosteroids
NSAIDs / COX-2 I
Musculoskeletal pain
Tricyclic anti-depressants

26. 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

28. 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: 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: mcg: 3-4 hours, mcg: hours
Methadone
Duration of analgesia: Oral: 4-8 hours, increases to hours with repeated doses
Half-life elimination: hours

29. 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

30. 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

31. 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)

32. 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.

33. 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

34. Opioid Analgesic Usual Starting Dose
Drug
Equianalgesic parenteral dose
Starting iv dose
iv:po ratio
Starting dose
po /transdermal
Duration of Action
Morphine
10 mg
Bolus dose= mg q 2-4 hours
Continuous infusion= mg/kg/hr
1:3
mg/kg/dose
q 4 hours
3-4 hours
Hydromorphone
1.5 mg
mg/kg q 4
1:5
0.06 mg/kg
q 3 to 4 hours
2-4 hours
Oxycodone
5-10 mg
N/A
mg/kg q 3 to 4
Fentanyl
100mcg
1 to 2 mcg/kg/hr as continuous infusion
25 mcg patch
72 hours
Methadone
0.1 mg/kg q 4 to 8 hours
1:2
0.2 mg/kg
q 4 to 8 hours
12 to 150 hours

35. 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

36. 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), mg Q 2-4 hrs prn.

37. 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.
from
100% to
50%
of new Opioid

40. Fentanyl

41. Conversion Table for Fentanyl
Morphine PO 3 1
Dilaudid IV 5 20
Dilaudid PO 2 8
Methadone PO 6
Oxycodone PO
1.5 10 4
Morphine IV
10 mcg IV Fentanyl =1 mg IV morphine
25 mcg TD Fentanyl/HR = 45 mg PO Morphine
IV Fentanyl 1:4 TD Fentanyl
200 mcg Actiq = 10 mg oxycodone
Morphine to Methadone ratio
30 to 90 mg morphine = 4:1
91 to 300 mg = 8:1
>300 mg =12:1
1mg IV methadone = 2 mg PO methadone

43. Patient –Controlled Analgesia

44. Disadvantages of Dosing with PCA
May increase adverse effects like
Sedation
Nausea
Respiratory depression

45. Clinical Questions

46. 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
Note: Ask students what this burning pain is (peripheral neuropathy) and what it may be due to (chemotherapy). Have students seen other cases of peripheral neuropathy on the wards (e.g. diabetic, alcohol)?

47. 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
Note: Ask students

48. 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

49. Answer #2 c. 10 mg IV q 4 hours Rationale:
Equianalgesic ratio for morphine is
1 mg IV = 3 mg PO.
When writing start time for the first dose, consider time of last oral dose.
ORAL DOSE (MG)
MED
PAREN-TERAL DOSE (MG) 30
Morphine 10
7.5
Hydro-morphone
(Dilaudid ®)
1.5 20
Oxycodone --
Hydro-codone

50. 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

51. 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.

52. 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

53. 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.

54. Equianalgesic Doses: Opioid Analgesics
ORAL DOSE (MG)
ANALGESIC
PARENTERAL DOSE (MG) 30
Morphine 10
7.5
Hydromorphone
(Dilaudid ®)
1.5 20
Oxycodone --
Hydrocodone
Note: before showing table ask students:
What is the most potent opiate they know?
Which ones are they comfortable using?
Do they know equianalgesic doses?
Handout laminated card.

55. 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

56. 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.

57. “Freedom from pain should be seen as a right for every cancer patient”
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”

58. THANK YOU