Combine modalities to enhance efficacy and minimize toxicity; monitor for cumulative adverse effects.
Core Pharmacologic Toolkit (WHO Ladder)
Non-opioids: acetaminophen; NSAIDs if platelet/renal/GI risk acceptable [4]
Opioids: titrate short-acting to effect; convert to long-acting with rescue for breakthrough; monitor sedation/constipation/nausea [4]
Neuropathic pain adjuvants: gabapentin/pregabalin; duloxetine/venlafaxine; TCAs (anticholinergic caution) [4]
Bone pain: bisphosphonates or denosumab; consider corticosteroids for capsular/edema-related pain [4]
Visceral/colicky pain: antispasmodics; consider celiac/splanchnic block for upper abdominal malignancy pain when refractory [4]
Nonpharmacologic Therapies (combine with drugs)
Cognitive-behavioral therapy and mindfulness: additive pain reduction vs pharmacotherapy alone in cancer pain [1]
Physical therapy/exercise and pacing; manual therapies as adjuncts [1]
Acupuncture and relaxation-based techniques where available [1]
Education, goal setting, and self-management skills; caregiver training [1]
Perioperative Multimodal Analgesia (Cancer Surgery)
Regional anesthesia and nerve blocks; local anesthetic infiltration [6], [2]
Scheduled acetaminophen/NSAIDs unless contraindicated; gabapentinoids with caution [6], [2]
Opioid-sparing adjuncts (ketamine, dexmedetomidine) per protocol [6]
Structured pathways in head & neck cancer surgery: reduced OMEs with maintained or improved pain control [2]
Opioid Stewardship and Safety
Set functional goals; use lowest effective dose; avoid rapid escalation [4]
Prophylaxis: stimulant laxatives ± softener; antiemetics as needed [4]
Assess risk (sleep apnea, renal/hepatic impairment, concurrent sedatives); consider naloxone when risk high [4]
Monitor for hyperalgesia, cognitive effects; plan taper during remission or after procedures [4]
When to Escalate/Refer
Uncontrolled pain despite optimized multimodal therapy
Suspected neuropathic or plexus involvement needing interventional evaluation
High toxicity burden limiting systemic options
Complex psychosocial distress requiring specialized behavioral interventions [3], [5]
Follow-up and Reassessment
Frequent early reassessment (24–72 hours after changes); adjust for effect and adverse events
Document pain intensity, function, sleep, mood, and breakthrough episodes
Revisit goals-of-care and deprescribe when possible; maintain bowel and antiemetic plans
Integrate survivorship and end-of-life needs across the trajectory [4]