Jerry A. Barbee Jr., Pharm.D., Glenn Schulman, Pharm.D., Matthew Bailey, Meagan Balding

Unrelenting cancer pain cab be devastating. With the United States in the grips of an opioid crisis, substance abuse must not cloud the needs of patients with cancer who are genuinely seeking relief from pain and suffering. It has been shown that these patients are far less likely to exploit and overdose from opioids than those in the general population.

Nevertheless, clinicians have many legal restrictions when prescribing opioids, and some patients with cancer are hesitant to use this class of drugs because of the stigma of potential addiction. An estimated 14 million patients with cancer reside in the United States, and about 40% of those are afflicted with associated pain. The treatment paradigm is slowly shifting toward a multimodal approach (i.e., anticonvulsants, antidepressants and nonsteroidal anti- inflammatory drugs [NSAIDs]), but opioids remain the agent of choice for moderate to severe cancer pain treatment.

In the general population, when patients experience pain, it is usually the result of biological processes or injury. However, cancer pain is unique to those who are affected by either its manifestations or treatments.

As a tumor enlarges, it can damage or exert pressure on nerve endings within the surrounding affected area. Additionally, certain types of cancer cells and other cells that surround tumors can release damaging or irritating chemicals that result in pain, such as the peptides bradykinin, endothelin-1 and tumor necrosis factor-alpha and the protein known as nerve growth factor. Cancers or tumors are not solely responsible for inducing pain, as many patients experience discomfort related to their treatment (e.g., chemotherapy, radiation or surgery).

Patients have reported different types of pain, including mixed, neuropathic or nociceptive, over the course of their disease’s progression. Nociceptive pain is caused by stimuli or tissue injury that has the potential to cause additional damage, whereas neuropathic pain is characterized by damage or dysfunction of the nervous system.

Pain treatment should be individualized based on causes, characteristics, clinical condition and patient goals, according to the European Society for Medical Oncology guidelines. Patients’ pain intensity, signs and symptoms should dictate treatment decisions.

Pain may present as somatic pain, which can be related to disease manifestations, such as metastatic bone cancer and skeletal muscle inflammation. Standards for the treatment of somatic pain include acetaminophen, NSAIDs and skeletal muscle relaxants. Visceral pain is associated with internal organs and can be related to organ compression or tumor infiltration. Neuropathic pain can arise from nerve damage because of cancer treatment-related complications and tumor infiltration. Based on the suspected pathophysiology (abnormal function in the body due to disease or injury) and pharmacotherapy (treatment with medicines), anticonvulsants (gabapentin and pregabalin), antidepressants (duloxetine and tricyclic antidepressants) and NSAIDs can be used to target and ease disease-related suffering.

Prolonged opioid use causes increased risk and incidence of opioid-induced constipation, nausea, itching and neuro- toxicity. This constipation can significantly reduce quality of life and has proved challenging to treat. Symptoms of opioid- induced neurotoxicity include hallucinations, hyperalgesia (heightened sensitivity to pain) and myoclonus (muscle spasms), which can be severe but managed via opioid rotation and rehydration as deemed appropriate. Concomitant medications during cancer treatment, including those — like Adriamycin (doxorubicin) &mdash; that might inhibit the cytochrome P450 enzyme (made by the body), may complicate treatment by further inducing opioid toxicity or decreasing analgesic effects through drug-drug interactions.

Some patients at risk of developing opioid use disorders may be asked to participate in regular pain-management consults and can be overseen by multidisciplinary teams. These teams are formed according to the patient’s specific needs and can aid in psychological and social aspects of opioid use disorder to prevent further opioid dependence through education.

Despite their undesirable side effects, opioids remain first-line therapy for moderate to severe pain in patients with cancer. Neuropathic-targeted treatments continue to be at the forefront of cancer pain management and are the focus of new and improved drug regimens. Using drugs to target some of the body’s receptors, such as melatonin receptor types 1 and 2, and employing newer agents, such as the cannabinoids (found in marijuana), may be prospective advances in the treatment of neuropathic pain. Medications such as cannabidiol (CBD), melatonin and quetiapine (an antipsychotic drug) have had their treatment roles expanded.

The patient and prescriber are often intertwined in challenging clinical and personal battles to manage pain. Clinicians must optimize pharmacotherapy to improve patients’ quality of life, and patients are encouraged to report their pain and ask not only about their options for treating it but also about the anticipated pros and cons associated with each of these therapies.

This article originally appeared in Pharmacy Times®, a sister publication of CURE®.

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Despite a national addiction crisis, opioids remain an appropriate choice for treating severe cancer pain.

Jerry A. Barbee Jr., Pharm.D., Glenn Schulman, Pharm.D., Matthew Bailey, Meagan Balding

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