Cancer pain management

Dr. Varun GoelMEDICAL ONCOLOGIST

RAJIV GANDHI CANCER INSTITUTE, DELHI

INTRODUCTION After Incurability, Pain the most fearful and the

most distressful symptom.

Inadequate Pain control profound alteration in nearly all aspect of wellness( activity-mood-rest-nutrition-sexuality..etc)

Optimal Pain control, may hasten a return to normality (function-physiologic-spiritual-psychologic,economic,vocational,survivorship)

INTRODUCTION Def. - A unpleasant sensory and emotional

experience associated with actual or potential tissue damage or described in terms of such damage. ~25% - newly diagnosed patients ~ 33% - patients undergoing treatment ~ 75% - with advanced disease.

Fortunately, 70-90% of pt. got adequate pain control with stabilized guideline

The rest 10-30% of pt. need more invasive procedures

Origin either (T-T-T)Tumor related: 60-80% of patientsTherapy induced: 20-25% of patients

a-Chemotherapyb-Radiotherapyc-Post surgical syndrome

Totally unrelated: 3-10%

Cancer Pain Syndromes

Pain syndromes associated with tumor infiltration • Metastatic bone pain • Retroperitoneal lymphadenopathy pain • Liver capsule pain • Headache • Cranial neuralgias • Glossopharyngeal neuralgia • Trigeminal neuralgia • Perineal pain

Postradiation pain syndromes

• Radiation fibrosis of brachial plexus

• Radiation fibrosis of lumbosacral plexus

• Radiation myelopathy

• Radiation-induced peripheral nerve tumors

Pain syndromes associated with cancer therapy Postsurgical pain syndromes

• Postmastectomy pain • Postradical neck dissection pain • Post-thoracotomy pain • Phantom limb and stump pain

Postchemotherapy Cisplatin, OxaliplatinPaclitaxil, ThalidomideVincristine, Vinblastine

• myalgias, arthralgias,

• peripheral neuropathy • Steroid pseudorheumatism • Aseptic necrosis of bone • Headache

Pain syndromes unrelated to cancer or

cancer therapy

• Lumbar disk disease • Osteoarthitis

NOCICEPTIVE

Injury – somatic and visceral structure

So subdivided into somatic - Sharp, well

localized, throbbing and pressure like

visceral pain – diffuse, aching or cramping

After surgical procedures, bone metastasis, infilteration or distension of viscera

NEUROPATHIC

Injury – PNS or CNS

Burning, sharp or shooting

Adverse effects of chemothepray or radiotherapy

Physiological effects of Pain

Increased catabolic demands: poor wound healing, weakness, muscle breakdown

Decreased limb movement: increased risk of DVT/PE

Respiratory effects: shallow breathing, tachypnea, cough suppression increasing risk of pneumonia and atelectasis

Increased sodium and water retention (renal) Decreased gastrointestinal mobility Tachycardia and elevated blood pressure

Psychological effects of Pain

Negative emotions: anxiety, depression

Sleep deprivation

Existential suffering

Immunological effects of Pain

Decrease natural killer cell counts Effects on other lymphocytes not yet

defined

ASSESSMENT OF PAIN

no objective measurement of pain pain history is the key to assess it

Intensity of pain is the most difficult and frustrating characteristics of pain to pinpoint

Few scales and tests are available.

COMPREHENSIVE PAIN ASSESSMENT

Detailed history type and quality of pain, onset, duration, course, intensity (i.e., pain experienced at rest; with movement; interference

with activities); location, radiation of pain; the associated factors that exacerbate or relieve the pain,

current pain management plan and patient’s response prior pain therapies; important psychosocial factors

patient distress, family and other support, psychiatric history

Diagnose the etiology and pathophysiology (somatic, visceral, or neuropathic) of the pain.

PAIN ASSESSMENT SCALES

UNIDIMENSIONAL SELF REPORT SCALES

Very simple, Useful

Valid method to assess

VERBAL DESCRIPTOR SCALES

Five word scaling

MILDDISCOMFORTINGDISTRESSINGHORRIBLEEXCRUCIATING

DISADV:

Limited selection of descriptorsPt. tend to select moderate grades than

extremes.

VERBAL NUMERIC RATING SCALE

On a numeric scale 0 to 10

0-no pain

10-worst pain imaginable

ADVANTAGES:• Simplicity, reproducibility, easy comprehensibility• Sensitivity to small changes in pain• Children at 5 years, who can count and have concept about

numbers can use this scale

VISUAL ANALOG SCALE(VAS)

Similar to verbal numerical scale

except that the pt. marks on a measured line, one end of which is labeled NO PAIN and other end WORST IMAGINABLE PAIN, where the pain falls

MULTIDIMENSIONAL INSTRUMENTS

• Provides more complex information about pt pain

• Time consuming

Multidimensional Tools

Measurement Tools

Validated pain and symptom assessment scales in adults and children

-- MPQ- McGill Pain Questionnaire

-- BPI - Brief Pain Inventory

-- MPAC - Memorial pain assessment card

-- MSAS - Memorial Symptom Assessment Scale

-- ESAS - Edmonton Symptom Assessment Scale

The McGill Pain Questionnaire

McGILL PAIN QUESTIONNAIRE (MPQ)

• Most frequently used multidimensional test• Descriptive words from three major

dimensions of pain (sensory, affective, evaluative) are further sub-divided into 20 sub-classes each containing words of various degrees

• 3 scores are obtained one from each dimension and total score is calculated

• Reliable and used in clinical research

BRIEF PAIN IN VENTORY (BPI)

• Patients are asked to rate the severity of their pain at its “worst “,”least” or “average” within the past 24 hrs. and at the time the rating is done.

• It also requires the patient to represent the location of their pain on a schematic diagram of the body

• BPI correlates with activity, sleep and social interaction.

Memorial pain assessment card

Rapid to use Correlated with other measures

 Card is folded along broken line so that each measure is presented to the patient separately in the numbered order

Barriers to Effective Cancer Pain Management

despite the availability of straight forward, cost effective therapies, Cancer Pain remains undertreated

Related to Health Care Professionals

Barriers

Inadequate knowledge of management Poor assessment of pain Concern about:

regulation of controlled substances side effects of analgesics tolerance to analgesics

Fear of patient addiction

common patient-related barriers to pain management

Drugs .. are addicting should be saved for

when it is really needed

have unpleasant or dangerous side effects

pills are not as effective as a shot

narcotics are only for dying people

Institutional barriers

Lack of commitment to make pain treatment a priority

Lack of resources Lack of use of instruments for pain

assessment

Strategies to Attack Cancer Pain

1) Eliminating or modifying the source of pain 2) Modifying the interpretation of the pain

message at the level of CNS

3) Interrupting the pain signalEn route from periphery to the CNS

It has been proved that pain modification at multiple site is an effective therapy.

Modify the source of pain Surgery (acute pain-post surgical pain syndrome) Radiotherapy(post radiation pain) Chemo and Hormonal Therapy

Modify the interpretation of pain message Pharmacological Analgesics Psychological support and Relaxation tech.

Pharmacological Analgesics First line of treatment

WHO Analgesic Ladder and NCCN guideline Oral route as long as possible

Three levels of pain intensity Mild pain (1-3) Moderate pain (4-6) Severe pain (7-10)

Pain

Step 1Nonopioid± Adjuvant

Pain persisting or increasing

Step 2Opioid for mild to moderate pain±Nonopioid ± Adjuvant

Pain persisting or increasing

Pain persisting or increasing

Step 3Opioid for moderate to severe pain

±Nonopioid ±Adjuvant

WHO Analgesic Ladder

Mild Pain

Moderate Pain

Severe Pain

Step 1: Acetaminophen & NSAID

Acetaminophen (paracetamol,). Equipotent to aspirin no anti-inflammatory or antiplatelet actions.

The starting dose is 650 mg PO q.i.d. and the maximum is 4,000 mg/day.

NSAIDS Mechanism: Cyclooxygenase inhibitor (COX-1

and COX-2)

PG E2 degradation

Decrease pain by reducing pain receptor sensitivity, reduce the inflammatory process and edema

Salicylates Aspirin is the standard against which other NSAIDs are

compared. Aspirin should not be used in patients with a h/o the

syndrome of nasal polyps and asthma, gastritis, peptic ulcer disease, or bleeding diathesis (including severe thrombocytopenia or concomitant use of anticoagulants).

Cyclo-oxygenase (COX) inhibitors divided into nonselective and selective COX-2

inhibitors. COX-1 - present in most tissues, helps maintain

gastric mucosa, and influences kidney and platelet function.

COX-2 - induced in response to injury and involved in the inflammatory cascade

The nonselective inhibitors can cause gastric ulcers and GI bleeding as well as affect platelet function.

The selective COX-2 inhibitors have relatively reduced the risk of GI toxicity and reduced antiplatelet effect.

NSAID-induced ulcer disease may be reduced by the Co-administration of H2 blockers or proton

pump inhibitors such as omeprazole (20 mg PO daily).

Misoprostol 100 mcg PO q.i.d. can also ameliorate the GI side effects.

Nonopioid Analgesics for Mild to Moderate Pain

Class Generic Name Dosing ScheduleRecommended Starting Dose

(mg)Maximum Dose (mg)

Salicylates Aspirin q4–6h 2,600 6,000

Choline magnesium

trisalicylateq12h 200 600

p-Aminophenol

derivative

Acetaminophen

(paracetamol)q4–6h 2,600 4,000

Propionic acids Ibuprofen q4–8h 1,200 3,200

Fenoprofen q4–6h 800 3,200

Ketoprofen q6–8h 150 300

Naproxen q12h 550 1,100

Naproxen sodium q12h 550 1,100

Acetic acids Etodolac q6–8h 600 1,200

Ketorolac q6h 15–30 q6h IV, IM 10 q6h PO 120 IV, IM 40 PO

Fenamates Meclofenamic acid q6–8h 150 400

Mefenamic acid q6h 500 × 1, then 250 q6h 1,000

COX-2 inhibitor Celecoxib qd–q12 100 200

Step 2 and 3: Opioids

Alter the unpleasant emotional experience associated with pain

provide pain relief through the interaction with specific opioid receptors - primary effect centrally.

The only significant differences among the various

opioids are duration of action and the dose needed to produce the same analgesic effect.

No “ceiling” to opioid doses exists. Doses can be escalated to provide analgesia as long as there are no unacceptable toxicities.

Ineffectiveness observed while using opioids usually indicates underdosing; Ineffectiveness may also reflect progression of the underlying disease

Can be classified into three groups:   

1) Morphine-like opioid agonists that bind competitively with and receptors (e.g., μ κcodeine, fentanyl, hydromorphone, morphine, oxycodone, and methadone)  

2) Opioid antagonists that have no agonist receptor activity (e.g., naloxone)  

3) Mixed agonists-antagonists (e.g., pentazocine and butorphanol) or partial agonists (e.g., buprenorphine)

Opioids

Step 2 opioids Codeine, Oxycodone, tramadol, hydrocodone

Step 3 opioids Oxycodone, morphine, fentanyl, methadone

AVOID: meperidine, agonists/antagonists, combo agents

Meperidine -repetitive intramuscular administration is associated with local tissue fibrosis and sterile abscess.

Repetitive dosing can also lead to accumulation of normeperidine, an active metabolite that can produce central nervous system hyperexcitability.

characterized by subtle mood effects followed by tremors, multifocal myoclonus, and occasional seizures.

It occurs most commonly in patients with renal disease

Naloxone does not reverse meperidine-induced seizures, some case reports that the use of naloxone has precipitated generalized seizures in individual patients

Converting from an agonist to an agonist-antagonist could precipitate a withdrawl crisis in the opioids dependent patient.

Non opioids combinations containing codeine, oxycodone, and propoxyphene are available, but these combinations often contain less than the full dose of 650 mg of aspirin or acetaminophen.

Prescribing each drug separately provides a better method for individualizing pain control

Opioid combination products

Typically used for Moderate episodic (PRN) pain Breakthrough pain in addition to a long-acting

opioid.

Never prescribe more than one combination drug at any one time.

Common Weak Opioids Percodan Oxycodone

5mgASA 325mg

Percocet Oxycodone 5mg

Acetaminophen 325mg

Lorcet Hydrocodone 10mg

Acetaminophen 650mg

Tylenol#3 #4

Codeine 30mgCodeine 60mg

Acetaminophen300mg

DHC plus Dihydrocodeine 16mg

Acetam.356mgCaffeine 30mg

Common Strong OpioidsGeneric Trade Route Equi.doses Duration.av

g

Morphine(MS)

MSIR ParenteralOral

10mg30mg

3-4 hr

MS.(S.R) MS Contin Oral 30mg 8-12 hr

Hyro-Morphone

Dilaudid ParenteralOral

1.5mg7.5mg

3-4 hr

Methadone Dolophine ParenteralOral

20mg10mg

4-8 hr4-8 hr

Levorphanol

Levo-Dromoran

ParenteralOral

2mg2mg

4-8 hr

Oxycodon SR

Oxycontin Oral 30mg 12 hr

How To Use Opioids? Pure agonist as first line of therapy. Higher

incidence of psychotomimetic effect (dysphoria-hallucination) and nausea and vomiting with A-A

Never mix agonist with agonist-antagonist Don’t mix two agonist Oral route whenever possible Round the clock strategy-----important

Continue…… NEVER PRN. Continuous pain need

continuous analgesic. Prevent resurgence of pain rather to treat it. It is only acceptable for break through pain.

Equianalgesia

- Determining equal doses when changing drugs or routes of administration

Use of morphine equivalents

Drug Equianalgesic I.V. or I.M. Dose (mg)

Morphine 10

Oxymorphone 1

Hydromorphone 1.5

Methadone 10

Levorphanol 2

Fentanyl 250 mcg

Incomplete cross-tolerance If a switch is being made from one opioid to another it

is recommended to start the new opioid at ~50% of the equianalgesic dose.

This is 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

In the opioid naive patient, the initial dose of MS - 5 to 30 mg depending on the severity q4h.

In the opioid naive patient with severe pain, initial MS doses of 2 to 4 mg IV or SQ can be given every 15 minutes as necessary to control pain.

When pain is controlled, total dose given becomes the q4h dose

In the elderly patient, it is always best to “go low” and “go slow.”

Once the optimal dose is found, the total opioid amount is calculated and then divided by two to yield the q12h, long-acting dose.

Opioid Dose EscalationAlways increase by a percentage of the present dose based upon patient’s pain rating and current assessment

Mild pain 1-3/10

25% increaseModerate pain4-6/10

25-50% increase Severe pain7-10/10

50-100% increase

If pain constant/chronic – use long-acting opioids with short-acting for breakthrough

Baseline Pain = Extended release morphine

Breakthrough = 10-20% increase.

Other routes for opioids

Rectal The oral–rectal potency ratio is 1:1. Oxymorphone, hydromorphone and morphine

suppository

Sublingual and buccal more lipophilic opioids such as fentanyl and methadone. The buccal–oral potency ratio is 1:1.

Topical opioids. It is available in a 1 mg/mL gel vehicle

Fentanyl patch

Simple, thin good adhesion Fentanyl in dissolved state with no

ethanol as permeation enhancer

Can be divided Guarantee stable blood fentanyl level for

72 h

Opioid Side Effects Constipation – need proactive laxative use

Oral naloxone effective in treating constipation, but it may reverse analgesic effect of opioids.

methylnaltrexone and alvimopan are peripherally acting antagonists. Prevent constipation without interfering analgesia

Nausea/vomiting – consider treating with dopamine antagonists and/or prokinetics (metoclopramide, domperidone, prochlorperazine [Stemetil], haloperidol)

Urinary retention Itch/rash – worse in children; may need low-dose

naloxone infusion. May try antihistamines, however not great success. Oxymorphone has reduced histaminic effects.

Respiratory depression – uncommon when titrated in response to symptom

naloxone to reverse it. But an ET tube should be placed before giving this.

Drug interactions Neurotoxicity (OIN): delirium,

myoclonus ® seizures

Drug interactions with opioids

Potentiators -by interfering with morphine metabolism. H2 blockers, antidepressants, phenothiazines,

and antianxiety agents. decrease – by induce the metabolism of

morphine. phenytoin, barbiturates, and rifampin.

MS effect on other agents. Morphine can increase gabapentin levels

Co Analgesics

Definition Agents which enhance analgesic efficacy, have independent analgesic activity for specific

types of pain, and / or relieve concurrent symptoms which exacerbate

pain

Adjuvants

Antidepressants TCAs for neuropathic

pain Anticonvulsants Corticosteroids Neuroleptics Alpha2 – agonists

Benzodiazepines Antispasmodics Muscle relaxants NMDA-blockers Systemic local anesthetics Antihistaminics

Adjuvants Bone pain

Bisphosphonates Calcitonin

Pain from malignant bowel obstruction Steroids Octreotide Anticholinergics

Adjuvant drugs Corticosteroids are indicated in

refractory neuropathic pain, bone pain, pain associated with capsular distension (painful

hepatomegaly), duct obstruction headache associated with central nervous system (CNS)

metastasis, bowel obstruction, and ascites.

Adjuvant drugs Bisphosphonate

for bone pain and fracture prevention from osteolytic lesions of multiple myeloma.

may also be helpful in controlling bone pain in up to 25% of patients with breast cancer or prostate cancer.

Analgesics for Neuropathic Pain

Tricyclic antidepressants Anticonvulsants

Gabapentin, Carbamazepine, Pregaba Local anesthetics

Parenteral, oral, topical Topical capsaicin Opioids

Neuropathic pain syndromes

Typical doses are as follows:

Gabapentin starting dose is 300 mg PO HS. The maximal dose is 6,000 mg/day with q.i.d. dosing.

Phenytoin(Dilantin), 100 mg b.i.d.; increase by 100-mg increments q3-7d.

Carbamazepine(Tegretol), 100 mg b.i.d.; increase by 100-mg increments q3-7d.

Lamotrigine(Lamictal), 25 mg PO h.s.; increase dose q3d

Topiramate(Topamax), 25 mg PO h.s.; increase dose q3d

Valproic Acid(Depakote), 200 to 400 mg PO b.i.d. or t.i.d.

Neuropathic pain syndromes

Antidepressants are useful adjuvant analgesics at doses below that needed to treat depression.

Tricyclic antidepressants, include amitriptyline , desipramine , nortriptyline , doxepin , and imipramine .

These are started at 10 to 25 mg h.s. and titrated upward at 10- to 25-mg increments every 5 to 7 days.

Selective serotonin reuptake inhibitors (SSRIs) include fluoxetine , paroxetine , sertraline , citalopram , and fluvoxamine .

These drugs have performed inconsistently in neuropathic pain trials.

Neuropathic pain syndromes

Systemic local anesthetics IV lidocaine.

Response occurs at sub–anti-arrhythmic doses but lasts only a few hours.

Mexiletine(Mexitil) The starting dose is 50 mg t.i.d. PO (taken with meals) with

titration upward every 5 to 7 days.

Topical agents Lidocaine patch, 5%(Lidoderm). On 12hrs off 12 hours (but can

leave on 24)

Topical capsaicin depletes substance P and may act as a counterirritant.

Results in trials are mixed for peripheral neuropathy and pain may actually worsen. It is not recommended.

Topical opioids

Non-Pharmacologic Management

Acupuncture Yoga Cold/heat Massage Vibration TENS units

Exercise programs Hypnosis Counseling Music

Transcutaneous electrical nerve stimulation (TENS) has demonstrated efficacy in the treatment of malignant disease, problems encountered were waning effect and

sudden termination of effect.

The results of clinical trials on acupuncture have been conflicting; retrospective data suggest - any efficacy of

acupuncture for cancer pain is short lived.

Psychological methods of pain control.

Behavioral modification not generally effective for moderate to severe chronic

cancer pain, may be helpful for mild pain. Operant conditioning, hypnosis, guided imagery, and biofeedback are techniques that can be helpful for

chronic mild pain,

Role of Invasive Procedures Optimal pharmacologic management

can achieve adequate pain control in 80-85% of patients The need for more invasive modalities

should be infrequent When indicated, results may be gratifying

These procedures are not for patients a short life expectancy in poor physical condition

Neuroablative procedures

Unilateral chordotomy - most effective neuroablative procedure

useful for patients with unilateral cancer pain below the shoulder.

Radiofrequency lesions to spinothalamic tracts of the spinal cord are generally placed at the C-1 to C-2 level.

Contralateral loss of superficial, deep, and visceral pain is produced in >75% of patients treated with percutaneous chordotomy.

The duration of analgesia is limited to only a few months;

incapacitating dysesthesia may develop after several months.

Sleep apnea, fecal and urinary incontinence, loss of orgasm, and muscle weakness, on the other hand, frequently complicate bilateral chordotomy.

Neuroablative procedures

Nerve blocks may be useful in patients with pain restricted to a single somatic nerve or adjacent nerves (e.g., postthoracotomy pain may be relieved by subcostal blocks).

Celiac plexus nerve block - effective in up to 85% of patients for treating upper abdominal visceral pain, particularly from cancers of the pancreas or stomach.

Lumbar sympathetic blockade - for pelvic visceral pain.

It affects sphincter tone or lower extremity strength uncommonly.

Pain

Step 1±Nonopioid± Adjuvant

Pain persisting or increasing

Step 2Opioid for mild to moderate pain

±Nonopioid ± Adjuvant

Pain persisting or increasing

Pain persisting or increasing

Step 3Opioid for moderate to severe pain

±Nonopioid ±Adjuvant

Invasive treatments

Opioid Delivery

Modified WHO Analgesic Ladder

Proposed 4th Step

The WHOLadder

Deer, et al., 1999

Thank you…