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Cancer pain is a very common symptom among cancer patients. Poorly controlled cancer pain leads to poor physical and emotional well being. Despite guidelines and availability of analgesia including opioids, under-treatment of cancer pain is common.

At a CME Talk, Dr Kok Jaan Yang, Senior Consultant in Palliative Medicine at Parkway Cancer Centre, discussed general principles of cancer pain management, the use of WHO (World Health Organisation)’s 3-step analgesic ladder for cancer pain as a guide, and some practical tips when using common analgesics.

General Principles of Cancer Pain Management for the Primary Doctor

Cancer pain management begins with a comprehensive assessment to determine the cause(s) and the severity of the pain, treating the underlying cause(s) of the cancer pain where possible, and selecting the appropriate analgesic based on the WHO’s 3-step Ladder. It is also important to maintain good communication with the patient and their family, explaining the management plan and addressing their concerns. Frequent reviews are also needed to monitor side-effects and to titrate the analgesics.

In cancer pain, it is useful to distinguish between nociceptive pain and neuropathic pain, as the choice of analgesic will be different. Nociceptive pain is usually opioids responsive while neuropathic pain is usually opioids semi-responsive. Adjuvants for neuropathic pain may be added if the neuropathic pain is not well controlled with opioids.

Using WHO’s 3-Step Ladder Analgesic for Cancer Pain

This guideline is still very useful for healthcare workers to choose the appropriate analgesia based on pain intensity. Up to 90% of cancer pain can be controlled using this guideline.

Step 1 – Use non opioid drugs such as paracetamol and Non-Steroidal Anti-Inflammatory Drugs (NSAID)s for mild cancer pain.

Step 2 – Use weak opioids such as tramadol or codeine for moderate cancer pain.

Step 3 – Use strong opioids such as morphine, oxycodone or fentanyl for severe cancer pain.

Adjuvants for neuropathic pain can be added at any of the 3 steps. Analgesics should preferably be given round the clock (maintenance analgesia) and during spikes in pain (rescue dose for breakthrough pain). The analgesia should preferably be given via oral route.

Another way to use the WHO’s 3-Step Ladder is by the multi-modal approach. It begins with the use of both Step 1 drugs, paracetamol and NSAIDs, for all cancer pain if there is no contra-indication. Step 2 drugs like tramadol are added if pain is not well controlled despite optimal doses of Step 1 drugs. If adding optimal doses of tramadol still does not control the pain, this Step 2 drug is replaced with a Step 3 drug of strong opioids such as morphine, oxycodone or fentanyl.

Practical Tips for the Common Analgesic

Paracetamol may provide additional pain relief when added to other classes of analgesic (multi-modal approach) so do not dismiss it. NSAIDs are a very useful class of analgesic but should be used with care in patients with gastric ulcer/bleeding, renal impairment and thrombocytopenia. Tramadol is preferred over codeine as the weak opioid of choice in cancer pain management and it has dual actions – opioid receptor agonist for nociceptive pain and as a Noradrenaline Serotonin Reupdate Inhibitor (SNRI) for neuropathic pain. Avoid Tramadol if the patient is on certain anti-depressants due to a potential for the development of Serotonin Syndrome.

For strong opioids, Morphine is considered the gold standard and is available in Singapore in all 3 types - immediate release oral liquid, sustained release oral tablet and injection formulation. Oxycodone is a good alternative strong opioids and is also available in 3 types: immediate release oral capsule OxyNorm®, sustained release oral tablet OxyContin-Neo® and injection OxyNorm®. Targin® tablet is a combination drug of OxyContin-Neo® and naloxone. Targin® is recommended in patients with opioid-induced constipation but should be used with caution in patients with liver impairment.

Targin® and OxyContin-Neo® are a sustain-release formulation and should not be used as a rescue dose. Use OxyNorm® or other immediate release strong opioids as a rescue dose. Fentanyl is another good strong opioid, which comes in a transdermal patch and an injection formulation. Fentanyl is the opioid of choice for patients with chronic kidney disease stage 4 or 5 and for those with swallowing and compliance issues. Avoid Pethidine injection totally in the management of cancer pain.

Dr Tan Tee Yong, Consultant Anaesthesiologist at Mount Elizabeth Hospital, followed up with further discussion on neuropathic cancer pain management. This is one of the most difficult types of pain to treat as it cannot be explained by a single aetiology, mechanism or anatomical lesion. Nearly 70% of this type of pain is caused by the malignancy while around 43% is caused by the cancer treatment.

Principles in managing Neuropathic Cancer Pain can be summarised in the following three ways:

1. Dampening down the peripheral sensitisation in the damaged axon with sodium channel blockers,
2. Dampening down central sensitisation with NMDA antagonists or calcium channel blockers, and
3. Enhancing descending inhibitory pathways with Tricyclics or Tramadol.

TCAs and gabapentin / pregabalin are both recommended first-line treatments for neuropathic pain.

As pain progresses, the use of multimodal analgesia techniques have been found to improve pain outcomes.

Using opioid rotation

Opioid rotation can be achieved by rotating the choice of opioid or/and mode of opioid administration. Such therapeutic changes have been shown to provide up to 70% improvement in therapeutic benefit, as it enhances drug efficacy and reduces the side effects experienced by the patient.

Intravenous infusion therapies

Intravenous Ketamine, Lignocaine and Dexmedetomidine intravenous infusion therapies can be used together with opioids during inpatient scenarios to improve cancer pain management.

Ketamine is a non-competitive inhibitor of NMDA receptors. Its role is mainly an "anti-hyperalgeic" and an "anti-opioid tolerant" agent, rather than an analgesic per se. Overall, use of intravenous ketamine can lead to an improvement in pain score and reduction in total opioid consumption in patients with opioid refractory cancer pain.

Lidocaine blocks sodium channels in the neuronal cell membrane to manage neuropathic and inflammatory pain.

Dexmedetomidine is a highly selective a2 adrenoceptor agonist. It is 8 times more specific for a2 adrenoceptors compared to Clonidine. Dexmedetomidine can be used in refractory cancer pain and allows patients to be sedated but communicative and cooperative. It is also an effective analgesic, allowing for the reduction in opioid consumption and pain intensity.

Dexmedetomidine infusion also helps to reduce anxiety, causes no respiratory depression and mimics natural sleep among other benefits. Its most common adverse effects are bradycardia and possibly concomitant hypotension.

Cancer pain can and should be treated. Doctors treating patients experiencing uncontrolled cancer pain should refer them to cancer pain specialists for better pain treatment options.