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ESMO Guidelines on management of cancer pain

ESMO Guidelines on management of cancer pain

The European Society for Medical Oncology (ESMO) has released clinical practice guidelines on the management of cancer pain in adult patients. The guidelines are published in the journal Annals of Oncology. 



  • The intensity of pain and the treatment outcomes should be assessed regularly and consistently using the visual analogue scale (VAS) or numerical rating scale (NRS) using the question: ‘What has been your worst pain in the last 24 hours?
  • Observation of pain-related behaviors and discomfort is indicated in patients with cognitive impairment to assess the presence of pain.
  • The assessment of all components of suffering, such as psychosocial distress, should be considered and evaluated.

Principles of pain management

  • Patients should be informed about pain and pain management and should be encouraged to take an active role in their pain management.
  • The onset of pain should be prevented by means of around-the-clock (ATC) administration, taking into account the half-life, bioavailability, and duration of action of different drugs.
  • Analgesics for chronic pain should be prescribed on a regular basis and not on an ‘as required’ schedule.
  • The oral route of administration of analgesic drugs should be advocated as the first choice.

Treatment of mild pain

  • Analgesic treatment should start with drugs indicated by the WHO analgesic ladder appropriate for the severity of pain.
  • There is no significant evidence to support or refute the use of paracetamol alone or in combination with opioids for mild to moderate pain.
  • There is no significant evidence to support or refute the use of NSAIDs alone or in combination with opioids for mild to moderate pain.

Treatment of mild to moderate pain

  • For mild to moderate pain, weak opioids such as tramadol, dihydrocodeine, and codeine can be given in combination with non-opioid analgesics.
  • As an alternative to weak opioids, low doses of strong opioids could be an option, although this recommendation is not currently part of WHO guidance.
  • There is no evidence of an increase in adverse effects from the use of low-dose strong opioids instead of the standard step 2 approach with weak opioids.

Also Read: Chronic Cancer Pain Management Guidelines

Treatment of moderate to severe pain

Strong opioids

  • The opioid of the first choice for moderate to severe cancer pain is oral morphine.
  • The average relative potency ratio of oral to i.v. morphine is between 1:2 and 1:3.
  • The average relative potency ratio of oral to s.c. morphine is between 1:2 and 1:3.
  • Fentanyl and buprenorphine (via the t.d. or i.v. route) are the safest opioids in patients with chronic kidney disease stages 4 or 5 (estimated glomerular filtration rate < 30 mL/min).
  • A different opioid should be considered in the absence of adequate analgesia (despite opioid dose escalation) or in the presence of unacceptable opioid side effects [III, C].
  • The subcutaneous (s.c.) route is simple and effective for the administration of morphine, diamorphine, and hydromorphone and it should be the first-choice alternative route for patients unable to receive opioids by oral or transdermal (t.d.) routes.
  • Intravenous (i.v.) infusion should be considered when s.c. administration is contraindicated (peripheral edema, coagulation disorders, poor peripheral circulation and need for high volumes and doses).
  • i.v. administration is an option for opioid titration when rapid pain control is needed [III, B].

Scheduling and titration

  • Individual titration, e.g. normal-release morphine administered every 4 hours plus rescue doses (up to hourly) for breakthrough cancer pain (BTcP), is recommended in clinical practice.
  • Immediate and slow-release oral morphine formulations can be used to titrate the dose. Titration schemes for both types of the formulation should be supplemented with immediate-release oral opioids, prescribed as required for BTcP.
  • The regular dose of slow-release opioids can be adjusted to take into account the total amount of rescue morphine.

Management of opioid side effects

  • Laxatives must be routinely prescribed for both the prophylaxis and the management of opioid-induced constipation (OIC).
  • The use of naloxone in association with oxycodone or methylnaltrexone to control OIC may be considered.
  • Naloxegol has been shown to be highly effective in OIC [II, B], but, to date, there is no specific reported experience in the cancer population.
  • Metoclopramide and antidopaminergic drugs should be recommended for treatment of opioid-related nausea/vomiting.
  • Psychostimulants (e.g. methylphenidate) to treat opioid-induced sedation are only advised when other methods to treat this have been tried (e.g. rationalize all medication with a sedative side effect).
  • Mu receptor antagonists (e.g. naloxone) must be used promptly in the treatment of opioid-induced respiratory depression.

Medical cannabis

  • Immediate-release opioids should be used to treat BTcP that is opioid-responsive and for which background cancer pain management has been optimized.
  • Transmucosal fentanyl formulations (oral, buccal, sublingual and intranasal) have a role in unpredictable and rapid-onset BTcP.
  • There are indications for standard normal-release oral opioids (e.g. morphine) that include a slow-onset BTcP or a pre-emptive administration of oral opioids ∼30 minutes before a predictable BTcP triggered by known events.

Bone pain

  • All patients with painful bone metastases should be offered external beam radiotherapy (EBRT) and the prescription should be 8 Gy single dose.
  • Patients with recurrent bone pain after previous irradiation should be offered re-irradiation with a further dose of 8 Gy.
  • Stereotactic body radiotherapy (SBRT) should be considered for patients with oligometastases having good performance status and well-controlled primary sites, preferably within clinical trials.


  • Early diagnosis and prompt therapy are powerful predictors of outcome in metastatic spinal cord compression (mSCC).
  • The majority of patients with mSCC should receive RT alone but surgery should be considered for selected cases.
  • Hypofractionated radiotherapy (HFRT) regimens, including a single dose of 8 Gy, can be considered the schedule of choice while more protracted RT regimens may be used in selected mSCC patients with a predicted longer life expectancy.
  • Dexamethasone should be prescribed in patients with mSCC in a dose of 8–16 mg daily.

Targeted therapy and bone pain


  • In castrate-resistant prostate cancer patients, radium-223 is effective in reducing skeletal-related events (SREs), decreasing pain and improving survival.
  • Radioisotope therapy with strontium, samarium or rhenium can be effective in some cases but may cause bone marrow toxicity.

Bisphosphonates (BPs)

  • BPs may be considered as part of the therapeutic regimen for the treatment of patients with bone metastases in patients with a good prognosis.
  • BPs should be considered especially when pain is not localized or radiotherapy (RT) is not readily accessible.
  • Preventive dental measures are necessary before starting BP administration.


  • Denosumab is indicated as an alternative to BPs for the treatment of patients with metastatic bone disease from solid tumors and myeloma.
  • Denosumab is effective in delaying bone pain recurrence.
  • Preventive dental measures are necessary before starting denosumab administration.

Neuropathic cancer pain 

  • Cancer-related NP can be treated using opioid combination therapies and carefully dosed adjuvants when opioids alone provide insufficient pain relief.
  • Patients with NP should be given either a tricyclic antidepressant (TCA) or an anticonvulsant and be monitored for side effects.
  • Gabapentin, pregabalin, duloxetine, and TCA (doses ≤ 75 mg/day) are strongly recommended as single agents for NP first-line treatment.
  • Interventional treatments of NP are based on weak or inconclusive evidence and should be restricted to patients with NP syndromes other than those related to cancer.
  • There is a lack of evidence to support the routine use of ketamine in cancer NP.

Invasive management of refractory pain

  • Intraspinal techniques delivered and monitored by a skilled team should be included as part of the cancer pain management strategy.
  • Coeliac plexus block (CPB) appears to be safe and effective for the reduction of pain in patients with pancreatic cancer, with a significant advantage over standard analgesic therapy until 6 months.
  • Cordotomy should be available to patients with otherwise poorly controlled cancer-related pain.

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Source: With inputs from Annals of Oncology

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