Cancer Pain Management Clinical Practice Guidelines (2018)

European Society for Medical Oncology

Reviewed and summarized by Medscape editors

August 09, 2018

The clinical practice guidelines on cancer pain management were released on July 24, 2018, by the ESMO.[1]

Initial and ongoing assessment of pain should be an integral part of cancer care and indicates when additional comprehensive assessment is needed. The regular self-reporting of PI with the help of validated assessment tools is the first step toward effective and individualized treatment. The most frequently used standardized scales are the visual analogue scale (VAS), the verbal rating scale (VRS), and the numerical rating scale (NRS).

Assessment of the pain descriptors improves the choice of therapy. Pain can be nociceptive (caused by ongoing tissue damage, either somatic such as bone pain or visceral such as gut or hepatic pain) or neuropathic (caused by damage or dysfunction in the nervous system, such as in brachial plexopathy or in spinal cord compression by tumor).

Initial assessment of cancer-related pain for all patients should include the following:

Ask a key screening question, which is not paraphrased and is used consistently. That question should be, “What has been your worst pain in the last 24 hours on a scale of 0–10, where 0 is no pain and 10 is the worst imaginable?”

Monitor if the pain is <3.

Move to a more detailed assessment if the worst pain is ≥3 or if the patient is distressed by pain. This should also include average pain and pain “right now.”

Administer appropriate analgesic and reassess both pain and analgesic side effects.

Review analgesic regimen if side effects to prescribed analgesics are present and/or pain persists.

The onset of pain should be prevented by means of around-the-clock 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.


Analgesic drugs are only one part of cancer pain management, and an integrated approach to cancer pain management should be adopted, including primary antitumor treatments; interventional analgesic therapy and a variety of non-invasive techniques such as psychological and rehabilitative interventions.

Analgesic treatment should start with drugs indicated by the WHO analgesic ladder appropriate for the severity of pain. (Paracetamol is the mainstay of the first two steps of the WHO analgesic ladder in many countries.)

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.

There are few options to treat mild to moderate cancer pain before moving to strong opioids such as morphine. Tramadol, dihydrocodeine, and codeine are the widely available options.


There is widespread use of tramadol in palliative care, even though the data on its use are limited and adverse effects can be severe. Tramadol has a potential role on step 2 of the analgesic ladder, particularly if other step 2 drugs are not tolerated, but adequate studies comparing tramadol with other step 2 drugs (eg, codeine or dihydrocodeine) are missing.

Tramadol can have significant side effects, such as dizziness, nausea, vomiting and constipation. Tramadol affects serotonin metabolism or availability, potentially leading to serotonin toxicity, particularly in the elderly, and can lower seizure thresholds. Tramadol has a much-reduced analgesic effect in cytochrome P450 2D6 (CYP2D6) poor metabolizers.


Dihydrocodeine is also a substrate for CYP2D6; its partial metabolism is limited in poor metabolizers and is blocked by CYP2D6 inhibitors. However, there is no evidence that such inhibition reduces its analgesic effect.


Codeine has no or little analgesic effect until metabolized to morphine, mainly via CYP2D6. In poor metabolizers, it is therefore essentially ineffective, while in ultrarapid metabolizers, it is potentially toxic.

Moderate to Severe Pain

Strong opioids are the mainstay of analgesic therapy in treating moderate to severe cancer-related pain. Although a variety of strong opioids exist and there is no superiority of one over another, morphine is the most widely available and prescribed. The average relative potency ratio of oral to IV morphine is between 1:2 and 1:3. The average relative potency ratio of oral to SC morphine is between 1:2 and 1:3.

Oxycodone or hydromorphone, in both immediate-release and modified-release formulations for oral administration, and oral methadone are effective alternatives to oral morphine.

Transdermal (TD) fentanyl and TD buprenorphine are best reserved for patients with stable opioid requirements; however, the use of lower strength TD fentanyl preparations in patients with unstable opioid requirements requires examination. The TD route is usually contraindicated during the titration phase, in opioid-naive patients, or to control breakthrough cancer pain (BTcP). TD fentanyl can be useful in patients with nausea, vomiting, problems with swallowing, constipation and poor compliance.

For advanced cancer patients with pain not fully alleviated by opioid therapy, the additive effect of nabiximols to the ongoing opioid treatment remains unclear. There is a need for further double-blind, placebo-controlled clinical trials with large sample sizes in order to establish the optimal dosage and efficacy of different cannabis-based therapies.


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