Transcript Pain in Cancer Patients

Management of Pain
in Cancer Patient
Dr. Khaled Abulkhair, PhD
Medical Oncology SCE, Royal College, UK
Ass. Professor of Clinical Oncology
Mansoura University, Egypt
Purpose
• Review
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basic principles of pain
management and analgesic therapy in
cancer patients.
Case study illustrating common pain
problems and suggested management.
Self evaluation
Pain in Cancer Patients
What is pain?
• An unpleasant feeling occurring as a result of injury or
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disease, usually localized in some part of the body.
Bodily suffering characterized by such feelings.
Mental or emotional suffering; distress.
Incidence:
• 30-40% of patients at time of diagnosis or during
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disease -modifying treatment.
70- 90% in those with advanced disease.
Pain is unpleasant sensation! Yet
protective
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Unlike other types of pain!
Severe, sharp and short
In healthy people
Severe, Sharp, chronic in
unhealthy patient
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Pain in Cancer Patients
Aetiology
• Direct tumour involvement: 62-78%
• As a result of diagnostic or therapeutic interventions
19-25%
– Post- radiation ( enteritis; nerve injury; osteonecrosis)
– Post-chemotherapy ( e.g. mucositis; peripheral neuropathy)
– Post- operative pain- acute and chronic
• Cancer induced syndromes <10%
– Constipation, pressure sores, shingles
• Pain unrelated to malignancy or treatment 3-10%
Direct Invasion by Cancer
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Large Lytic Metastases
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Bed Sores
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Types of Pain
• Acute:
e.g. procedural pain; pathological fracture;
bowel/ureteric obstruction
• Chronic
• Acute on Chronic (Breakthrough pain)
• Malignant; Non-Malignant
Types of Pain
• Nociceptive: Direct response to tissue
injury
Includes musculoskeletal (somatic) and
visceral pain
• Neuropathic: Pain associated with
damage to the nervous system
• Mixed pain syndromes
Untreated Pain….. Patients and caregivers need to
understand that pain is important. There is an
urgency. If pain is not controlled, their lives are out
of control.
Impact on
• Function
• Sleep
• Impaired cognitive
function
• Quality of life
Outcomes
• Depression
• Decreased
socialization
• Increased health care
utilization
• Increased costs
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“Pain is a more
terrible lord of mankind
than even death itself ”
Albert Schweitzer
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Outcome of cancer Pain Management
There’s more to cancer care than simply
helping patients survive. There's more to
cancer treatment than simple survival.
- > 80% will achieve good control
- 15% will have fair control
- < 5% will have poor or no control
Principles of Cancer Pain Management
• Start early……
• The most important step in treating pain is the
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assessment.
Oral route is preferred when available. Although the
ratio of oral to parenteral morphine is commonly
noted to be 6:1, clinical observation of chronic cases
indicates that this ratio is closer to 3:1.
Choose the analgesic drug and dose to match the degree
of pain suffered by the patient.
Before adding or changing to another drug, maximize the
dose and schedule of the current analgesic drug.
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• For persistent severe pain, use a product with a long
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duration of action. Pain medications should always be
administered on a scheduled basis or around the clock. It
is always easier to prevent pain from recurring than to
treat it once it has recurred.
As-needed dosing should be used for breakthrough pain.
If more than two as-needed doses are required for
breakthrough pain in a 24-hour period, consider
modifying the regimen.
Provide medications to prevent adverse events such as
constipation and itching.
Use appropriate adjuvant analgesics and nondrug
measures to maximize pain control.
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Abdou
• 83 year old widower: Lives alone
• Ca Prostate with Bony metastases; Hx
OA/ IHD/ Depression
• Brought in by daughter: Won’t leave
the house
• Increased pain in his shoulder and
lower back for 2 weeks
• Constipated
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Pain Assessment Tools
• Listen carefully: What are the words used?
May deny pain but will admit to having “discomfort”,
“aching” or “soreness”
 Do you hurt anywhere?
 Are you uncomfortable?
 How does it affect you?
• Because pain is subjective, it is best evaluated by the
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patient (i.e., not a caregiver and not the health
professional).
Believe the patient “pain is what the patient says
hurts….the best judge of a patient’s pain is the
patient” Bonica.
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OPQRSTUV
O NSET: When did it start?
P ATTERN: How often; When; How long?
Q UALITY: Describe it: sharp, dull...Colic
R ELIEVING/AGGRAVATING FACTORS
S EVERITY: Scale of 1- 10
T REATMENTS: What helps; For how long
U NDERSTANDING: What do you think is
causing it?. How does it affect you?
V ALUES: Goals Of Care; expectations
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Tools
Please rate your pain by circling the one number that best describes your pain
_____________________________________________________________
0
1
2
3
4
5
6
7
8
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10
What is your Pain at it’s
Best / Worst/ Present/ Average
No Pain
Pain as bad as you can imagine
In the past 24 hours, how much RELIEF have pain treatments or medications
provided? Please circle the one percentage that most shows how much.
_____________________________________________________________
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
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Pain History: Abdou
• O(nset): Several months/  2 weeks
• P(attern): R shoulder/lower back pain. Constant.
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Increased with movement (what would be named?).
Q(uality): Steady aching pain
R(elief): Medication helps for about 2-3 hrs
S(everity): 6/10. 10/10 with movement
T(reatments): T#3 helps for about 2-3 hours. Takes
about 12-15 T#3 a day
U(nderstanding): Not going on any Morphine. I’m not
dead yet.
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Examination
• No evidence of fractures but clearly
limited ROM in the shoulder due to pain
• No vertebral tenderness and no
neurological signs
• Bowel and bladder function normal…yet
constipated
• X-rays show bony mets. in shoulder and
lumber spine
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Abdou– approach to treatment
Develop a problem list to resolve
 Somatic / bone pain
 Acetaminophen dosing too high (~4
Gm)
 Constipation contributing to pain
intensity
 Compliance issues
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• Do not under-estimate the
patient’s condition based on
his denial.
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How would you better manage
Abdou’s pain?
DRUGS
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Pain Management is not only drugs
Educate patient and family:
- Myth: “Save it for ..when it gets worse”
• FACT: Treating early prevents pain
• FACT: No ceiling effect of strong opioids
- Myth: “I’ll become addicted”
• FACT: Addiction is rare. Boston study- 0.03%
• FACT: Tolerance is rare in Palliative Patients/PO
route.
- Myth: Treatment worse than pain
• FACT: Side effects can be managed/treated
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Education
Constant pain requires regular dosing
Avoid peaks of pain as with prn dosing
Smoother blood levels can provide more
consistent pain control
More convenient
Less analgesia over time
Maintain uninterrupted sleep
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Morphine
WHO 3-step Ladder
Hydromorphone
Methadone
Fentanyl
Oxycodone
± Adjuvants
Codeine
Oxycodone
± Adjuvants
Acetaminophen
NSAIDs
± Adjuvants
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Drugs for Pain Management
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Acetaminophen
NSAIDS
Opioids
Adjuvants/ Co analgesics
A.
Bisphosphonates/Calcitonin
B.
Antidepressants
C.
Anti-convulsants
D.
Disease specific therapies:
Radiation/Chemotherapy/Surgery
E.
Steroids
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Analgesics
• Step 1: Mild pain:
– Acetaminophen: Max 2.4 gm/day
Can be very effective for mild-moderate pain if
given regularly…caution with Hepatic patients.
– NSAIDs: Issues re GI and renal toxicity
Concerns in the elderly...
Non-specific: Use with GI protection
COX 2 agents safer re GI morbidity and
antiplatelet effects
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NSAIDS
• Both peripheral and central effects
• Inhibit cyclo-oxygenase (COX) enzyme -> 
Decreased prostaglandin production
• Specific COX 2 inhibitors: Celecoxib, rofecoxib.
Less GI effects
• Less effect on platelet function
“Non-Selective” COX 2 inhibitors: Diclofenac
Nonacetylated salicylates: Diflunisal
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NSAIDs
• Ibuprofen Q4-6h, Max 2400 mg/day
• Diclofenac Potassium, Cataflam, Q 8-12h, Max 150
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mg/day…first day 200 mg.
Diclofenac Sodium, Voltaren, Q 8-12h, 150
mg/day.
Indomethacin Q8-12h, Max 200 / day
Naproxyn Q 12h, max1650 mg/day
Meloxicam Q24h, Max 15mg/day
Tenoxicam, Epicotel, Q24h, max 20 mg
Celecoxib Q12h, Max 400mg/day
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Step 2 + 3 Opioid Use
 Opioids help relieve moderate to severe pain ( and
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dyspnea in terminal patients).
Opioid receptors have been targeted for the treatment
of pain and related disorders for thousands of years.
 they produce analgesia primarily by inhibiting
nociceptive transmission in the central nervous system
 Episodic pain - Prescribe as needed
 Constant pain = Regular dosing PLUS a
“breakthrough” PRN dose
 Right drug at the Right dose
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Step 2: Moderate pain
Tramadol…PO, IV …
• variable responses…
• Max…400 mg/day
• Constipation and mode changes
• Myths
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Codeine…..Co
Weak Opioid
 About 10% of population lack enzyme to
convert to Morphine
 Ceiling effect: > 600 mg/day
 Very constipating
 Combination product or alone
 Helpful for persistent pathological cough.
 1:10 ( Morphine : Codeine)
 Sustained release preparation :
Codeine Contin 50,100,150, 200 mg
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Oxycodone:
Moderate ->Strong Opioid
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Active at the mu and kappa receptors
Safe with decreased renal function
Potency Oxycodone 1.5 - 2 :1 Morphine
Less constipating than Codeine
Lasts ~ 4-5 hours
No ceiling effect/help Neuropathic pain
Alone or with ASA/Acetaminophen
OxyContin 10, 20, 40, 80 mg
Start slow stop slow
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Strong Opioids
• Morphine still is the gold standard
– Concerns re: metabolites in renal failure;
elderly….Liver impairment.
–Extensive first pass metabolism
• Hydromorphone:
– More soluble.
– Few metabolites
– 5x more potent than Morphine.
Opioid Pharmacology
• Cmax = 60 mins (after PO dose)
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45 mins (after SC dose)
30 mins (after IM dose)
6 mins (after IV dose)
t1/2 = 3-4 hours
Duration = 20-24 hrs (immediate-release)
48-72 hrs (sustained-release)
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Strong Opioids
• Fentanyl: Not at mu
receptor. More lipophilic
– 100x more potent than
Morphine.
– Less constipation and
nausea.
– Less histamine release
– Useful in true opioid
allergy
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Fentanyl
• Transdermal Patch: different strengths in mcg/hour:
25 ~ 100 mg Morphine/day (45 -134)
50 ~ 200 mg (135-224), 75 (225-314),
100 ~ 400 mg (315-404 mg M/day)
Takes ~17 hours to reach steady state
Patch lasts 72 hours in 90% of patients
• Sublingual, intranasal, subcutaneous, IV routes
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Methadone
• Semisynthetic used in maintenance treatment for opioid•
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dependent individuals as well as in patients taking
opioids long term for moderate to severe pain
Has activity not only at the opioid receptors, but also at
the NMDA (N-methyl-d-aspartate) receptor
Complex pharmacokinetics with extended half-life,
which creates difficulties in dosing and transitioning
from one opioid to another
Associated with QT prolongation and/or torsades de
pointes
Effective long-acting agent; used for neuropathic pain
Start low and titrate slowly.
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Opioid Equi-analgesic Doses
http://agencymeddirectors.wa.gov/mobile.html
• 10 mg PO morphine
=5 mg SQ/IV morphine (half the oral dose)
= 100 mg PO codeine (1/10)
= 2 mg PO Hydromorphone (1mg SQ) (5x
more potent)
= 5 - 7.5 mg PO Oxycodone ( 1.5x)
= 0.5- 1 mg PO/pr methadone ( not Q4H) (
~~10 x more potent)
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Steps for converting between opioids
• Calculate total mg dose taken in past 24-hours.
• Determine equi-analgesic dose.
• If pain is controlled on current opioid, reduce the
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new opioid daily dose by 25-50% to account for
cross-tolerance, dosing ratio variation, and interpatient variability.
If pain is uncontrolled on the current opioid, increase
opioid daily dose by up to 100-125%.
Titrate liberally and rapidly to analgesic effect during
first 24 hours.
Monitor for adverse events and effectiveness.
Reassess the analgesic effect every 2-3 days.
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Abdou
Proposed Management Strategy?
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Abdou
• 12-15 T#3 = 350/30 mg not controlled
– 3900- 4875 mg Acetaminophen plus
– 360- 450 mg Codeine
~ 36- 45 mg PO Morphine TDD (total daily dose)
~ 7- 9 mg PO Hydromorphone
~ 25- 30 mg PO Oxycodone
~Patch?
• Concerns re Acetaminophen dose/ Approaching
ceiling Codeine
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Abdou
• Rotation to strong opioid:
• Which one?
• Dose: ? Equi-analgesic
- ? Increase dose
- BT (Break Through)
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Opioid Adverse Effects
• Constipation: “ The hand that writes
the opioid prescription should start the
laxative”
٠ Stimulant (+/- softener) (+/- osmotic)
٠ Nausea:
٠Approximately 50% will have some nausea in
first week; 30% after that
٠In those prone to nausea consider anti-emetic
(metoclopramide)
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Abdou: 2 days later
Morphine SR 30 mg BID = 60 mg
PLUS 6 BT of 5 mg
= 30mg
90mg
• Increase to morphine SR 45 mg BID
• BT: 10% of TDD or 1/2 of Q4H dose
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Bone Pain
What role would the following play?
Radiotherapy
NSAIDs
steroids
Bisphosphonates
calcitonin
What else might you do? Spiritual
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Breakthrough Pain
• End of dose pain:
 Usually requires dose increase regular
medication
• Paroxysmal/Idiopathic:
Titrate to only 1-3 BT’s /day
BTD should be 10% of TDD/1/2 of Q4H
• Incident Pain
Precipitant. Peaks early. Short duration
65% last 30 minutes or less
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Ideal Analgesic
 Easily
administered
 Rapid onset
 Short-duration
of action
 In patient’s
control
 Before the event
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In Reality….Good and Bad
Side Effects
Expensive
In-availability
Tolerance
Toxicity
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Abdou: 3 months later
• Confused , drowsy
• Not eating
• Pain on any weight bearing, despite recent
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RXT, radiating into his Left leg
Some myoclonus
LAB: Normal Calcium, Creatinine 2mg/dl
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Abdou
Current medication:
٠ morphine SR 100 mg PO BID
٠ Also taking about 5 BT of 20 mg/day.
٠ 200 mg plus 100 mg = 300 mg morphine
TDD
What do you recommend re his pain
management?
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Abdou …Problem list?
Bone Pain with Incident Pain?
Opioid toxicity?
Neuropathic Pain?
New mets to brain or liver?
Constipation?
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Opioid Toxicity….augmented by
renal impairment
Sedation
Constipation
Urine retention
Nausea / vomiting
Hyperalgesia
Agitated delirium
Myoclonus
Respiratory depression
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Opiate conversion:
Knowing he was taking Morphine 300 mg /day. What
dosage would you initiate the following with?
– Hydromorphone? X 5
– Oxycodone?
X 1.5 -2
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Key learning
- Give medication orally whenever possible.
- less invasive, effective, convenient, cost
effective analgesia.
- rapid onset of action with oral formulations can
be achieved with: IR opioids, certain
controlled-release opioids (e.g. CR oxycodone
or CR codeine)
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REMS: Risk Evaluation and Mitigation
Strategy for Extended-Release/LongActing Opioid Analgesics
On June 9, 2012, the FDA announced it
would require manufacturers of extendedrelease and long-acting opioid analgesics to
provide training for health care professionals
who prescribe these agents.
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Adjuvant analgesics
Drugs whose primary indication is other than pain; they
are used to manage specific pain syndromes. Most often,
adjuvant analgesics are used in addition to, rather than
instead of, opioids.
• Antidepressants
• Transdermal lidocaine
• Corticosteroids
• Benzodiazepines
• NSAIDs
• Bisphosphanates
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Bisphosphonates
• Family of drugs that prevents bone
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resorption by inhibiting osteoclasts.
Helpful in bone pains due to metastases.
Best in use is zoledronic acid (zometa),
given as 4 mg I.VI every 4 – 6 weeks.
Renal impairment is an issue.
Oral forms are available. Issues regarding
GIT upsets and nephrotoxicity.
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Radiation Therapy
• Effective in palliating pain
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from bone mets, soft tissue
masses.
60-70% Response rates.
Different machines,
energies and techniques.
Can be re-challenged.
Refer to a colleague
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Neuropathic Pain
• Pain that arises from injury, disease or dysfunction in the
peripheral or central nervous system.
• Incidence in Cancer : 30-50%
• Usually described as burning, numbness, stitching or crushing.
• Caused by (eg, trauma, ischemia, infections) or from ongoing
metabolic or toxic diseases, infections, or structural disorders
(eg, diabetes mellitus, amyloidosis, HIV infection, nerve
entrapment, etc) which produce afferent impulses and signal
damage to the nerve structures.
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Herpes Reactivation
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Treatment of Neuropathic Pain
• Treat early as central mechanisms can cause
persistence of pain
• Adjuvant medications are essential
• Titrate one medication at a time
• Push dose until pain relief or intolerable side
effects seen
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Opioids in Neuropathic Pain
Should always be tried
Individual variation
Methadone may be the most useful opioid
in neuropathic pain
Some evidence for oxycodone also being
more useful
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Antidepressants in Neuropathic
Pain
• Tricyclic antidepressants still the best
Effective in 50-65% of cases
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Nortriptyline = amitriptyline as first line
Desipramine for those who don’t tolerate
Starting dose 10 –25 mg
Usual therapeutic dose is 50 –150mg
Analgesic effect seen 4-7 days after reaching
therapeutic dose
• SSRI ..Escitalopram # Omeprazole
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Anticonvulsants in Neuropathic Pain
• Gabapentin … Try first
• Gabapentin has good evidence for efficacy
• Most respond to 2100 – 3600mg/day
• Push dose to 6000mg/day 80%of patient can
tolerate.
• Pregabalin (Lyrica):
• 75 -300 mg BID
• Max 600 mg/day
• Others: Carbamazepine; Clonazepam;
Phenytoin
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Miscellaneous Medications
• Corticosteroids useful with associated swelling
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and inflammation
Baclofen if associated with muscle spasm
Calcitonin 100-200 units/day helpful with
phantom limb pain and sympathetically
maintained pain
ketamine
Clonidine
Mexiletine, flecanide, lidocaine
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Self Evaluation Questions
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1- A 75-year-old man has metastatic prostate
cancer. The main sites of metastatic disease are
regional lymph nodes and bone (several hip
lesions). He experiences aching pain with
occasional shooting pains. The latter are thought to
be the result of nerve compression by enlarged
lymph nodes. He has been taking oxycodone- APAP
5 mg 2 tablets every 4 hours and ibuprofen 400 mg
every 8 hours. His current pain rating is 8/10, and he
states that his pain cannot be controlled. Which is
the best recommendation to manage his pain at this
time?
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A. Increase oxycodone-APAP to 7.5 mg/325
mg, 2 tablets every 4 hours.
B. Increase oxycodone-APAP to 10 mg/325
mg, 2 tablets every 4 hours.
C. Discontinue oxycodone-APAP, discontinue
ibuprofen, and add morphine sustained
release every 12 hours.
D. Discontinue oxycodone-APAP, and add
morphine sustained release every 12
hours.
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2-Which is the most appropriate adjunctive
medication for this patient’s pain?
A. Naproxen.
B. Single-agent (single ingredient) APAP.
C. Gabapentin.
D. Baclofen.
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3- A 60-year-old man has head and neck cancer with
extensive involvement of facial nerves. His pain
medications include transdermal fentanyl 100 mcg/
hour every 72 hours and oral morphine solution 40
mg every 4 hours as needed. He is still having
problems with neuropathic pain. Which treatment is
best to recommend?
A. Begin gabapentin and decrease the dose of
fentanyl.
B. Increase the doses of fentanyl and morphine.
C. Begin diazepam and increase the dose of fentanyl.
D. Begin gabapentin and continue fentanyl and
morphine.
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Summary:
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Comprehensive assessment is paramount.
Avoid unnecessary delay in treating pain.
Educate patient, family & caregivers.
It is not a one man show. Use multi-disciplinary
approach. Call your colleagues!
Choose medications based on stepped approach, as
well as side effect profile
Tailor medication regimens to meet individual needs.
Remember interactions and dose reductions in organ
failures.
Consider non-pharmacological options
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References
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Bruera et al. A prospective open study of oral methadone in
treatment of cancer pain. 9th World Congress on Pain, 2000
Lawlor PG, Turner KS, Hanson J, Bruera E. Dose ratio
between morphine and methadone in patient with cancer
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Ripamonti C. J Clinical Oncology, 1998
C Gannon. The Use of Methadone in the Care of the Dying,
EJPC, 1997
R Fainsinger, T Schoeller, E Bruera. Methadone in the
Management of Cancer Pain: A Review. Pain 52: 137-147,
1993
Bruera et al. Opioid Rotation in Patients with Cancer Pain.
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