Cancer Pain
from eTG and Cancer Pain Management: A Narrative Review of Current Concepts, Strategies, and Techniques Curr. Oncol. 2023, 30(7), 6838-6858; https://doi.org/10.3390/curroncol30070500
Key Principles
- Pain in palliative care differs due to:
- Irreversible disease trajectory
- Non-curative focus
- Shift from curative to emphasis on comfort, dignity, and patient preferences
- Pain often includes :
- physical dimension
- psychological dimension
- social dimension
- spiritual dimension
Unique Features
- Total pain concept includes suffering, existential distress, grief
- types of pain – often a combination
- Nociceptive – somatic or visceral
- Neuropathic – due to nerve compression or injury
- Incident – anticipated pain related to activity (e.g. moving, toileting, dressing changes)
CANCER PAIN
Sources
- Tumour: bone, nerve compression, organ capsular stretch
- Treatment: chemo-induced neuropathy, RT-induced injury
- Others: infection, paraneoplastic syndromes
Management
- Follow palliative pain pathway, plus:
- Radiotherapy for bone mets, nerve compression (response in 2–3 weeks)
- Corticosteroids for peritumour oedema (dexamethasone common)
- Chemotherapy/immunotherapy: only if benefits outweigh risks
BONE PAIN
- Often mixed nociceptive/neuropathic
- Multimodal approach:
- Opioid
- NSAID (if tolerated)
- Adjuvant (e.g. pregabalin)
- Radiotherapy = effective, but delayed onset
- Pathological fractures: surgical fixation may improve QoL
PAIN IN THE LAST DAYS OF LIFE
- Focus shifts to symptom relief over function
- SC route often preferred
- Use opioid infusions for continuous comfort
- Simplify regimens
- Avoid burdensome interventions
COMPREHENSIVE PAIN ASSESSMENT
Assessment Domains
- Cause of pain: tumour-related, treatment-related, comorbidities
- Type of pain:
- Nociceptive: somatic or visceral
- Neuropathic: tumour infiltration, treatment-induced
- Incident or breakthrough
- Severity:
- Mild: minimal impact on function
- Moderate: interferes with activity
- Severe: impairs daily function
Pain scores alone are insufficient; assess functional impact.
Contributing Factors
- Past response to treatments
- Comorbid organ dysfunction (renal, hepatic)
- Psychosocial context
- Cultural/language considerations
DEVELOPING A PAIN MANAGEMENT PLAN
Core Components
- Individualised plan considering:
- Prognosis
- Patient and family preferences
- Goals of care (pain relief vs preservation of cognition/mobility)
- Discuss risks/benefits of pharmacological and nonpharmacological options
- Include contingencies for:
- Escalation (e.g. refractory pain)
- Medication administration when oral route is not available
Tools and Strategies
- Cancer Council pain diaries/templates
- Regular multidisciplinary review
- Frequent reassessment as disease progresses
🔑 GENERAL STRATEGIES
Non-Pharmacological
- Education: clarify that pain relief is a goal, not always full eradication
- Energy conservation, pacing
- OT/PT input for pain-triggering tasks (e.g. movement, dressing)
Pharmacological
- Multimodal analgesia:
- Combine drugs with different mechanisms (opioid + adjuvant)
- Reduces required doses and side effects
- Start low, go slow, especially in frail patients or organ impairment
💊 PHARMACOLOGICAL MANAGEMENT BY PAIN TYPE
🔹 Mild to Moderate Pain
- Paracetamol (first-line unless contraindicated)
- NSAIDs (use with caution: GI, renal risks; avoid in last weeks of life)
🔹 Moderate to Severe Pain
- Opioids:
- Morphine, oxycodone, hydromorphone, fentanyl
- Oral route preferred; subcutaneous or IV when oral not possible
- Start with immediate-release for titration
- Use equianalgesic charts (e.g., eviQ calculator)
- Monitor for:
- Opioid-induced constipation: prescribe laxatives concurrently
- Sedation, cognitive changes, respiratory depression
🔹 End-of-Life Pain Management – Syringe Driver (SC)
Typical opioid SC infusion via syringe driver in last days of life:
| Medication | Usual SC starting dose (opioid-naïve) | Notes |
|---|---|---|
| Morphine | 10–15 mg/24h | Titrate based on PRN use |
| Oxycodone | 10 mg/24h | Alternative if renal impairment |
| Hydromorphone | 2–4 mg/24h | For frail or opioid-sensitive patients |
| Add Midazolam (e.g. 5–10 mg/24h) if anxiety or dyspnoea |
💊 Neuropathic Pain
Prevalence and Challenges
- Incidence: 20-40% of cancer patients experience neuropathic pain.
- Mixed Pain: Neuropathic pain often coexists with nociceptive pain due to tumor mass effect.
Diagnosis and Screening
- Comprehensive Evaluation: Diagnosis involves detailed history, physical examination, and possible diagnostic tests.
- Screening Tools: Tools like LANSS, DN4, and PainDetect can help assess neuropathic pain.
Treatment Approaches
- First-Line Medications:
- TCAs (amitriptyline, nortriptyline)
- SNRIs (duloxetine, venlafaxine),
- anticonvulsants (gabapentin, pregabalin).
- Topical Treatments: Lidocaine patches and high-concentration capsaicin for localized neuropathic pain.
- Combination Therapy: Often requires a combination of opioids and adjuvants.
- Specific Opioids for Neuropathic Pain: Tramadol and tapentadol, with dual mechanisms, are effective; methadone can be used for complex cases.
Adjuvants – Neuropathic Pain / Bone Pain / Spasm
| Medication | Indication | Dose | Notes |
|---|---|---|---|
| Amitriptyline | Neuropathic pain | 10–25 mg nocte | Anticholinergic SEs; avoid in elderly or delirium |
| Gabapentin | Neuropathic pain | Start 100–300 mg nocte ↑ slowly to 900–1800 mg/day | Adjust in renal impairment |
| Pregabalin | Neuropathic pain | 25–75 mg BD | Fewer cognitive SEs than gabapentin |
| Duloxetine | Neuropathic pain | 30–60 mg/day | May help with depression too |
| Dexamethasone | Peritumour oedema, nerve compression | 4–8 mg/day (short course) | Use morning dosing; taper gradually |
| NSAIDs (e.g. ibuprofen, celecoxib) | Bone pain, inflammation | Ibuprofen 200–400 mg TDS Celecoxib 100 mg BD | Risk: GI, renal, cardiac; avoid in final days |
| Baclofen / Diazepam | Muscle spasm | Baclofen: 5 mg BD Diazepam: 2–5 mg TDS PRN | Use caution with sedation |
🔥 BREAKTHROUGH PAIN
Definition and Incidence
- Definition: Transient exacerbation of pain in patients with controlled baseline pain.
- Incidence: 40-80%, higher in advanced disease.
Management Strategies
- Avoiding Triggers: Avoiding factors that provoke pain episodes and pre-emptive analgesia before interventions.
- Rapid-Onset Opioids: Use of lipophilic opioids like fentanyl or sufentanil administered transmucosally (sublingual, intranasal, oral).
- 1/12 to 1/6 of total daily opioid dose (eTG)
- Educate on timing and frequency
- Avoid automatic escalation of background dose unless frequent needs (>3/day)
- Optimizing Baseline Pain Control: Better baseline pain control can reduce BTP episodes. (eTG)
- Dosing for BTP: Controversy exists on whether to use doses proportional to background analgesia or titrated minimum doses. Further studies are needed.
Breakthrough dose = 1/12 to 1/6 of total 24h opioid dose, given PRN, q1–2h
| Drug | Route | Onset | Notes |
|---|---|---|---|
| Morphine IR | Oral | 30–45 min | Most commonly used |
| Fentanyl | Buccal/SL | 5–15 min | Use for incident pain with quick onset |
| Methoxyflurane | Inhaled | Immediate | Avoid regular use; use in procedures only |
| Ketamine | SC/IV | Rapid | Requires specialist oversight for refractory pain |
⚡ INCIDENT PAIN
- Anticipated pain related to activity (e.g. moving, toileting, dressing changes)
- Pre-emptive dosing:
- Short-acting opioids (e.g. transmucosal fentanyl)
- NSAIDs if inflammation is a component
- Modify activity and use OT/PT input
- Anxiolytics may help with procedure-related anxiety
🚨 ACUTE PAIN IN OPIOID-TOLERANT PATIENTS
Example (Severe Pain in Regular Opioid User)
- Oxycodone CR 60 mg BD → 120 mg/day
- Equiv to oral morphine 180 mg/day → IV morphine 60 mg/day
- Breakthrough IV dose = 5–10 mg morphine PRN
Avoid automatic background opioid increase based on incident doses.
Cancer Pain Management: A Narrative Review of Current Concepts, Strategies, and Techniques by François Mestdagh, Arnaud Steyaert and Patricia Lavand’homme – https://www.mdpi.com/1718-7729/30/7/500
Opioids in Cancer Pain Management: An Update of the Mainstay Approach
Importance and Guidelines
- Mainstay of Treatment: Opioids remain essential for managing moderate to severe cancer pain.
- Guidelines: Follow guidelines from EAPC, ASCO, ESMO, and WHO, which are regularly updated.
- WHO Three-Step Ladder: This approach has guided opioid prescribing since 1986.
Weak Opioids
- Recommendations: Codeine, hydrocodone, and tramadol for mild to moderate pain in opioid-naïve patients.
- Combination Therapy: Often combined with non-opioid analgesics like paracetamol/acetaminophen and NSAIDs.
- Efficacy: No significant evidence that starting with weak opioids improves overall pain management.
Strong Opioids
- Recommendations: Morphine, oxycodone, hydromorphone for moderate to severe pain.
- Dosing: Start with low doses and titrate to achieve optimal analgesia with tolerable side effects.
- Effectiveness: Over 90% of patients achieve meaningful relief with oral morphine or fentanyl patches within 10-14 days.
- Side Effects: 77% of patients experience side effects, primarily constipation and nausea, with 10-20% needing treatment changes.
Comparative Efficacy and Switching
- Efficacy Comparison: Similar analgesic efficacy among oral morphine, oxycodone, and hydromorphone, but patient response varies.
- Side Effects: Common side effects include constipation, nausea, drowsiness, and confusion. Less gastrointestinal side effects with transdermal fentanyl.
- Opioid Rotation: Switching between opioids or administration routes is common to optimize pain management, particularly for non-responders or poor responders.
Special Considerations for Specific Opioids
- Methadone: Effective in opioid switching due to unique properties but complex to convert; recommended for experienced professionals.
- Buprenorphine: Not first-line for cancer pain but used in opioid switching and for chronic pain in cancer survivors.
- Tapentadol: Effective for mixed and neuropathic pain, with dual mechanisms of action.
- Ketamine: Useful as an adjunct for refractory pain at sub-anaesthetic doses.
- Magnesium Sulfate and Lidocaine Infusions: Considered for complex pain management.
- Cannabis-Related Medicines: Limited evidence for chronic pain relief.
Optimizing Opioid Utilisation When Pain Remains Poorly Controlled
Causes of Poor Response
- Non-Responders/Poor Responders: Up to 26% of patients may not respond adequately to opioids.
- Factors: Disease progression, psychological conditions, presence of neuropathic pain, breakthrough pain, opioid misuse, tolerance, and hyperalgesia.
Strategies for Optimization
- Opioid Rotation: Switching opioids or administration routes to improve efficacy and manage side effects.
- Methadone: Recommended for opioid switching, particularly for high-dose opioid users, but requires specialist supervision.
- Adjuncts: Buprenorphine, tapentadol, ketamine, magnesium sulfate, and lidocaine infusions can be used as additional options for complex pain.
- Co-Analgesic Use: Methadone can be used in low doses as a co-analgesic with other opioids.
Adverse Effects and Harms Related to Long-Term Opioid Intake
Common Side Effects
- General Side Effects: Nausea, constipation, sedation, dizziness, hallucinations, and respiratory depression.
- Endocrine and Bone Health: Long-term use may cause endocrine changes and bone demineralization.
- Psychological Effects: Risk of depression and psychological dependence.
Opioid Use Disorders (OUD)
- Prevalence: OUD is a concern in cancer patients, with a prevalence of up to 20%.
- Management: Close follow-up and cautious prescribing, with efforts to taper opioids and use alternatives like buprenorphine.
COMPLEX SCENARIOS
Chronic Noncancer Pain
- Total pain freedom often unachievable
- Avoid aggressive opioid escalation
- Focus on comfort, not control
Substance Use Disorder
- Do not withhold analgesia
- Use defined doses, written agreements
- Monitor for misuse
- Early referral to pain/addiction/palliative specialists
- Avoid methoxyflurane or high-dose benzodiazepines with opioids
Opioids
- Morphine
- pure mu-agonist that is primarily metabolised in the liver.
- metabolites are renally excreted
- morphine use in patients with renal insufficiency is generally not recommended because of accumulation of metabolites and potential toxicities.
- Oxycodone
- binds to mu and kappa receptors
- available in a combination preparation with naloxone, to minimise the side effects of constipation.
- Naloxone
- opioid antagonist
- Poor oral bioavailability – only 2% reaches systemic circulation
- oral formulation of naloxone is not effective in reversing opioid overdose
- additionally Naloxone has limited penetration into the CNS when taken orally = reducing the likelihood of precipitating withdrawal symptoms.
- remains in the gastrointestinal tract 🡪 reduce constipation
- the oxycodone/naloxone combination should be avoided when there is moderate or severe hepatic dysfunction, as this may lead to increased serum levels of naloxone
- Naloxone
- Hydromorphone
- potent, hydrophilic opioid
- metabolites are renally cleared,
- Fentanyl
- highly lipophilic
- available in transdermal/ parenteral / transmucosal
- can be useful for chronic, stable pain
- Methadone
- mu-receptor agonist opioid with N-methyl-D-aspartate (NMDA) inhibitor properties.
- methadone can be very effective for refractory and complex cancer pain, the risk of accumulation and potential overdose means that it is best prescribed by a pain or palliative medicine specialist.
- Buprenorphine
- partial agonist is available in transdermal form
- Opioid rotation
- Switching from one opioid to another is recommended if a particular opioid fails to provide adequate analgesia, or rapid tolerance is seen, or if toxicity or adverse effects develop.
- Opioid rotation can improve response and/or reduce intensity of side effects
Opioids – First-line for Moderate to Severe Pain
from eTG
| Medication | Route | Starting Dose (Opioid-Naïve) | Notes |
|---|---|---|---|
| Morphine | Oral | 2.5–5 mg q4h PRN SR: 10–15 mg BD | Gold standard; caution in renal failure |
| SC/IV | 1–2.5 mg q2–4h PRN | Use 1/2 oral dose when converting to SC | |
| Oxycodone | Oral | 2.5–5 mg q4h PRN CR: 5–10 mg BD | Better tolerated in renal impairment |
| SC/IV | 1–2 mg q4h PRN | SC dose ≈ 50% of oral | |
| Hydromorphone | Oral | 1–2 mg q4h PRN ER: 4 mg daily | Potent; use in renal failure (with caution) |
| SC/IV | 0.25–0.5 mg q4h PRN | 5–7x potency of oral morphine | |
| Fentanyl | Transdermal | 12–25 mcg/hr patch q72h | Not for opioid-naïve; steady over 48h |
| SL (Breakthrough) | 100 mcg (titrate up) | Rapid onset, short duration (for incident pain) | |
| Methadone | Oral | 2.5–5 mg BD–TDS (specialist only) | Long half-life; complex kinetics; requires expert input |
Key Conversion Ratios (Approximate – use calculator to confirm)
| From | To |
|---|---|
| Oral morphine → SC morphine | Divide by 2 |
| Oral morphine → Oral oxycodone | Divide by 1.5 |
| Oral morphine → Oral hydromorphone | Divide by 5 |
| Oral morphine → Transdermal fentanyl | 60 mg/day ≈ 25 mcg/hr patch |
Always consult equianalgesic calculators (e.g., eviQ, ANZCA) and cross-check with pharmacy or palliative specialist.
Nausea management
- Serotonin antagonists (e.g., ondansetron, granisetron):
- Advantages:
- Serotonin antagonists are effective in managing nausea associated with chemotherapy-induced nausea and vomiting (CINV) and other causes.
- They have a rapid onset of action and can be administered orally, intravenously, or through other routes.
- They generally have a favorable side effect profile.
- Disadvantages:
- In some cases, serotonin antagonists may cause mild side effects such as headache, constipation, or dizziness.
- Rarely, they can lead to more serious cardiac arrhythmias, especially in patients with pre-existing heart conditions.
- Advantages:
- Dopamine antagonists (e.g., metoclopramide, prochlorperazine):
- Advantages:
- Dopamine antagonists are effective in managing nausea and vomiting in various palliative care settings.
- They work by blocking dopamine receptors in the brain.
- Metoclopramide also has prokinetic properties, which can be beneficial in managing gastric stasis or delayed gastric emptying.
- Disadvantages:
- Dopamine antagonists can cause side effects such as sedation, extrapyramidal symptoms (e.g., involuntary movements), or hyperprolactinemia (increased levels of prolactin hormone).
- Advantages:
- Corticosteroids (e.g., dexamethasone):
- Advantages:
- Corticosteroids have anti-inflammatory properties and are effective in managing nausea associated with chemotherapy, brain tumors, or other causes.
- They also have potential antiemetic effects.
- Disadvantages:
- Prolonged use of corticosteroids may be associated with side effects such as increased appetite, weight gain, mood changes, or immunosuppression.
- However, in the palliative care setting, short-term use is usually well-tolerated, and the benefits often outweigh the risk
- Advantages:
- Hyoscine
- acts by blocking the action of acetylcholine in the central nervous system.
- Disadvantages
- Side effects: dry mouth, blurred vision, drowsiness, confusion, and urinary retention. Anticholinergic effects: cognitive impairment and delirium in vulnerable populations, particularly older adults
- Limited evidence base: While hyoscine is sometimes used in palliative care for managing nausea, the evidence supporting its efficacy in this context is limited compared to other antiemetic medications, such as serotonin antagonists or dopamine antagonists.