What is the best approach for managing pain in a patient with metastatic cancer?

Managing Pain in Metastatic Cancer

For a patient with metastatic cancer requiring better pain control, initiate or escalate opioid therapy using the WHO analgesic ladder approach: start strong opioids (morphine 20-40 mg oral daily as first-line) with around-the-clock dosing plus breakthrough doses, and rapidly titrate to effect within days. 1, 2

Initial Pain Assessment

Evaluate pain intensity at this visit using a numerical rating scale (0-10) or visual analog scale to guide treatment decisions. 1, 2 Characterize whether the pain is:

• Nociceptive (aching, throbbing, pressure-like from tumor infiltration or bone metastases)
• Neuropathic (shooting, sharp, stabbing, tingling from nerve compression)
• Mixed (combination of both types)

This distinction is critical because neuropathic pain requires adjuvant medications beyond opioids alone. 1, 2

Pharmacologic Management Based on Current Pain Severity

For Severe Pain (NRS 8-10 or inadequately controlled moderate pain)

Start strong opioids immediately—do not waste time with weak opioids if pain is severe. 1, 2

First-line opioid choice:

• Oral morphine remains the gold standard: start 20-40 mg daily in divided doses (immediate-release every 4 hours or sustained-release every 12 hours). 1
• Alternative strong opioids if morphine is not tolerated or available: oxycodone 20 mg daily (2x more potent than oral morphine), or hydromorphone. 1, 3

Critical dosing principles:

• Provide around-the-clock scheduled dosing for persistent pain—not "as needed" administration. 1, 2
• Prescribe breakthrough doses equal to 10-15% of the total daily dose for transient pain exacerbations (typically immediate-release morphine every 1-2 hours as needed). 1, 2
• Titrate rapidly by increasing doses every 1-3 days until adequate pain control is achieved—there is no ceiling dose for pure opioid agonists. 1, 2, 4
• If the patient requires more than 4 breakthrough doses daily, increase the baseline around-the-clock opioid dose. 1

For Moderate Pain (NRS 5-7)

If the patient has moderate pain and is opioid-naive, you can start with either:

• Low-dose strong opioids (morphine 20 mg daily)—preferred if progressive pain is anticipated. 1, 2
• Weak opioids (tramadol 50-100 mg, codeine, or dihydrocodeine 60-120 mg) combined with non-opioid analgesics. 1, 2

However, in metastatic cancer with progressive disease, starting directly with strong opioids is often more practical to avoid the need for rapid escalation. 1

For Mild Pain (NRS 1-4)

Continue or add non-opioid analgesics:

• Acetaminophen/paracetamol up to 4000 mg daily. 1, 2
• NSAIDs (ibuprofen up to 2400 mg daily, naproxen up to 1000 mg daily) with gastroprotection (PPI). 1, 2

Managing Neuropathic Pain Components

If the pain has neuropathic features (common with nerve compression from tumor), add adjuvant analgesics in combination with opioids:

• Gabapentin: Start 100-300 mg at bedtime, increase by 50-100% every few days to target dose of 900-3600 mg daily in 2-3 divided doses. Adjust for renal insufficiency. 1
• Pregabalin: Start 50 mg three times daily, increase to 100 mg three times daily (up to 600 mg daily). More efficiently absorbed than gabapentin. Adjust for renal insufficiency. 1
• Antidepressants (duloxetine 30-60 mg daily up to 120 mg, or venlafaxine 50-75 mg daily up to 225 mg) for neuropathic pain. 1

Special Considerations for Bone Metastases

Bone metastases cause both baseline pain and incident (movement-related) breakthrough pain:

• Increase baseline opioid doses above what controls pain at rest to prevent movement-related pain flares—this requires higher doses than traditional titration. 5
• Consider radiotherapy for localized bone pain—this has specific efficacy and is essential for pain relief. 1
• Add bisphosphonates or denosumab for bone pain management. 2, 6
• Rapid-onset fentanyl (buccal or nasal) is strongly recommended for breakthrough cancer pain due to faster onset than oral morphine. 6

Managing Opioid Side Effects Proactively

Anticipate and prevent common side effects:

• Constipation (occurs in nearly all patients): Start prophylactic stimulant laxatives (senna) plus stool softener immediately when starting opioids. 1, 2
• Nausea/vomiting: Prescribe antiemetics (metoclopramide, ondansetron) for the first week. 1
• CNS toxicity (drowsiness, confusion, hallucinations, myoclonus): If intolerable despite dose adjustment, perform opioid rotation (switch to alternative opioid at 50-75% equianalgesic dose). 1, 6

Alternative Routes When Oral Route Fails

If the patient cannot take oral medications:

• Parenteral morphine: Use 1/3 of the oral dose (e.g., 5-10 mg IV/SC starting dose). 1
• Transdermal fentanyl: Reserve for patients with stable opioid requirements ≥60 mg oral morphine daily (start 25 mcg/hr patch). Do not use for rapid titration. 1, 7
• Continuous subcutaneous infusion: Medically preferred invasive route if needed. 8

Psychosocial Support and Patient Education

Essential messages to convey:

• Relief of pain is medically important—there is no benefit to suffering. 1
• When opioids are used to treat cancer pain, addiction is rarely a problem. 1
• Pain medications work better when taken on a regular schedule for persistent pain. 1
• Many options are available if initial treatment doesn't work. 1
• Pain management is a team effort involving oncology, palliative care, pain specialists, and other disciplines. 1

Common Pitfalls to Avoid

• Do not delay strong opioids in patients with severe pain or metastatic disease—weak opioids are often inadequate. 1
• Do not use transdermal fentanyl for initial opioid titration—it is only for stable pain requirements. 1
• Do not prescribe opioids without breakthrough doses—cancer pain has unpredictable exacerbations. 1, 2
• Do not forget prophylactic laxatives—constipation is nearly universal and undertreated. 1
• Do not use methadone as first-line—reserve for difficult pain syndromes due to complex pharmacology and variable half-life. 1, 6

Monitoring and Rapid Adjustment

• Reassess pain intensity daily during titration using the same numerical scale. 2, 9
• Adjust opioid doses every 1-3 days based on breakthrough dose requirements and pain scores. 1, 2, 4
• If pain remains inadequately controlled despite optimal pharmacologic therapy, consider interventional approaches (nerve blocks, spinal analgesia, vertebral augmentation for spine metastases). 2, 9