Cancer pain is often the most debilitating and invasive aspect of cancer that a patient has to deal with, and is a very common occurrence especially in people with advanced cancer. Analysis from one study concludes that the prevalence of cancer pain is higher in head and neck, lung and breast cancers, in comparison to other cancers, and more than one-third of patients graded their pain as moderate or severe (van den Beuken-van Everdingen et al 2016).
Effective cancer pain management has a huge impact on the quality of life of people living through cancer, as well as on the perceived value of cancer treatment itself. Therefore, it is important for physicians to get it right when assessing pain and monitoring response to treatment.
Cancer pain can result from the cancer itself, interventions to treat the disease, or other underlying conditions, and can be classed as somatic, visceral, neuropathic, or a mix of both. Pain perception is not a purely physical experience, and so trying to get an accurate assessment of a person’s overall pain state is tricky. The Cancer Pain PDQ® (PDQ Supportive and Palliative Care Editorial Board) recommends the assessment of the physical, psychological, social, and spiritual components of pain in order to make a proper assessment. Once a physician establishes pain type, severity and whether cancer pain is acute, chronic or breakthrough, cancer pain management consists of the use of opioid, non-opioid, and adjuvant therapies (in addition to treating the primary disease). While cancer treatment options are becoming less reliant on the ‘blunderbuss’ chemotherapeutic approaches and moving towards more targeted therapies guided by molecular profiling of cancer, pain management relies to some extent on a blanket approach to treating pain. This is not entirely a bad thing, as current medications are reasonably effective in treating pain and are relatively inexpensive to administer.
Opioid treatment of cancer pain
For patients with moderate-to-severe pain, opioids occupy the second and third rung of the WHO’s analgesic ladder and have proven useful particularly in visceral and somatic cancer pain (neuropathic pain is thought to be less responsive to opioids), when non-opioid options such as paracetamol or NSAIDs don’t produce the desired effect. The first port of call is opioids like tramadol, codeine or low doses of strong opioids such as morphine or oxycodone. For more severe pain, morphine, oxycodone, fentanyl and methadone are amongst those available.
There are over 10 different opiate derivatives available, varying in potency, receptor selectivity and side effect profile, and a wide variety of administration routes have been developed, allowing opioid use to be tailored to the needs of the patient. Some oral formulations have seen opioids paired with an opioid antagonist (such as oxycodone/naloxone) to offset the constipating effects of opiates. Selecting the best opioid for the job seems to rely on clinicians experience with using the drug, patient factors such as the age group being treated and renal function, and cost (Patel et al 2014). Due to the fact that opioids target both the pain and reward systems in the central nervous system, opioid addiction and misuse are always a factor to consider, particularly with long-term use. Volkow and McLellan (2016) examine the opioid epidemic in the US and cover the misconceptions regarding opioids and addiction in the case of non-cancer chronic pain. Mitigating against risks of addiction, overdose, and opioid diversion involves engaging in regular monitoring, overdose risk assessment and participating in prescription drug monitoring programmes. As the level of physician interaction that cancer patients receive is justifiably greater than those with non-cancer pain, it may be easier to monitor cancer patients and prevent these risks from developing.
The development of opioid formulations that prevent abuse are already available (overviewed in Volkow and McLellan 2016), and it is likely that this type of drug development will continue. Trying to treat pain using a pharmacological approach, without identifying the molecular cause of that pain, falls short of addressing the root cause. For now, current pharmacologic treatment options are a good fit for many patients, but we have yet to fully un-muddy the waters surrounding cancer pain causes. Cancer-related neuropathic pain in particular appears to be difficult to reach with current opioid therapies, and treatment relies of other agents such as tricyclic antidepressants or gabapentin. As we learn more about the molecular states which perpetuate cancer pain (such as tumour-related growth factor expression, neuro-immune interactions and cytokine expression), molecular diagnoses will hopefully allow us to further target the sources of pain. Research into pain management is driven for those who don’t get relief from conventional treatment approaches, and so while the efficacy of opioids is a welcome ally in controlling cancer pain, this should not slow us from researching more targeted pain management drugs in future.