Disclosures: Balkrishnan reports a consultant/advisory role with Merck. Davis, Hashmi, Park and Roberts report no relevant disclosures.
September 24, 2020
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Opioid use among cancer survivors: Striking a balance

Disclosures: Balkrishnan reports a consultant/advisory role with Merck. Davis, Hashmi, Park and Roberts report no relevant disclosures.
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Opioids are a potent pharmacologic option for managing recurrent pain experienced by cancer survivors.

Due to the persistence and severity of cancer-associated pain, clinicians historically have not prioritized limiting prescriptions for these patients. However, concerns about inappropriate opioid use and addiction have led to increased caution in this regard.

Although physicians agree such caution is appropriate, some believe it is important that the pendulum not swing too far in that direction.

“There has been a paradigm shift in the thought process of clinicians, from never undertreating patients with cancer to restricting opioids, and I am afraid we may end up undertreating some patients who genuinely require opioids,” Sharukh K. Hashmi, MD, MPH, hematologist and public health specialist at Mayo Clinic in Rochester, Minn., and chair of the department of hematology/oncology at Sheikh Shakhbout Medical City in Abu Dhabi, United Arab Emirates, said in an interview with Healio. “There are reasons behind the rationales on both extremes. However, as an oncology medical community, we have fallen in the trap of availability heuristics by extrapolating the current national opioid crisis into a cancer opioid crisis.”

A ‘huge’ problem

Although some survivors may require opioids to cope with pain, inappropriate use of these drugs is “a huge and an underestimated problem,” Hashmi said.

Sharukh K. Hashmi, MD, MPH
Sarukh K. Hashmi

“Up to half of cancer survivors have been prescribed opioids at one time during their cancer survivorship, which starts at diagnosis,” he said.

Hashmi emphasized the need to distinguish opioid use from abuse. He said opioid use is the proper utilization of prescription medication for a physical illness that requires treatment.

“The term ‘abuse’ commonly refers to addiction, or more precisely substance use disorder [SUD] as defined by the DSM-5 [Diagnostic and Statistical Manual of Mental Disorders, fifth edition] criteria,” he said. “Now is the time for the medical community to avoid the word ‘abuse’ and refer to it by the DSM-5 terminology SUD, just as we replaced the word ‘narcotics’ with ‘opioids.’”

Hashmi said this change in terminology is important, because the word abuse is not only inaccurate but also humiliating to patients and taboo in some cultures.

“Notably, SUD refers to a reversible condition and, therefore, we should screen and evaluate for this condition routinely,” he said. “Equally important is to differentiate between physical dependency and addiction, as quite commonly these coexist, but sometimes only one is present, and the management may differ.”

A precise quantification of the prevalence and extent of SUD vs. appropriate use of opioids has been difficult, given limitations in our ability to measure provider intent and other unique patient circumstances.

A cross-sectional study by Jairam and colleagues assessed use and misuse of prescription opioids among 169,162 survey respondents, including 5,139 adult cancer survivors. The study showed higher rates of prescription opioid use, compared with a reference group of cancer-free adults, among both more recent cancer survivors (54.3% vs. 30.5%; OR = 1.86; 95% CI, 1.57-2.2) and less recent cancer survivors (39.2% vs. 30.5%; OR = 1.18; 95% CI, 1.08-1.28). Researchers observed similar rates of prescription opioid misuse among more recent (3.5%) and less recent survivors (3%) and the reference group (4.3%).

Prescription opioid misuse among survivors appeared to be associated with younger age (18-34 years vs. 65 years; OR = 7.06; 95% CI, 3.03-16.41), alcohol use disorder (OR = 3.22; 95% CI, 1.45-7.14) and nonopioid drug use disorder (OR = 14.76; 95% CI, 7.4-29.44).

Additionally, the study showed survivors of gallbladder, liver, pancreatic, larynx, windpipe, lung and cervical cancer reported the highest rates of opioid use or misuse, possibly due to several factors, according to senior study author Henry S. Park, MD, MPH, assistant professor of therapeutic radiology at Yale School of Medicine.

Henry S. Park, MD, MPH
Henry S. Park

“The cancers themselves may cause more pain, and the treatment required may also cause more pain,” Park told Healio. “Our data also suggest that patients diagnosed with a nonopioid substance use disorder may be more predisposed to misusing opioids, although this certainly is not the case for each individual patient.”

Park said overall, the study showed “a very low percentage of patients with cancer are using their prescription opioids inappropriately.” He said that in a separate project his group found prescriptions of opioids by oncologists and other clinicians have decreased significantly over the past several years.

“This may have to do with legislation, as well as physician guidelines and awareness of the dangers of prescription opioid misuse,” he said. “We are concerned that these limitations, which are often designed for patients without cancer, may be applied inappropriately to patients with cancer.”

Other potential risks

Prolonged opioid use may carry several potential health risks other than SUD, particularly for breast cancer survivors.

“One of the problems with adjuvant hormone treatment [for breast cancer survivors], and many of these survivorship treatments, is that they can be associated with musculoskeletal side effects,” Rajesh Balkrishnan, PhD, professor of public health sciences at the University of Virginia School of Medicine, told Healio. “It is often recommended that women take some type of commonly available painkiller and exercise to improve muscle tone. But many women require short courses of opioids to manage their pain.”

Balkrishnan said his research showed that a significant number of survivors used opioids much longer than normally recommended, and that these women had a tendency to discontinue adjuvant hormone treatment.

“We’ve done several studies over a period of time that have shown that women who adhere to adjuvant hormone therapy show greater survival and a lower incidence of tumor recurrence,” he said. “It’s a very effective treatment for most women after their first course of treatment for breast cancer. The idea of women discontinuing this treatment is a scary concept.”

In some cases, opioid use may even worsen or extend the pain it is meant to relieve.

“[Opioids] can increase the unpleasantness of pain and produce hyperalgesia to certain pain sensations, such as the cold,” Mellar P. Davis, MD, FCCP, FAAHPM, director of palliative care services at Geisinger Health System in Pennsylvania, told Healio. “There may be less tolerance to pain, and so people’s pain may improve by reducing their opioids.”

Mellar P. Davis, MD, FCCP, FAAHPM
Mellar P. Davis

Davis said opioids may interfere with internal mechanisms that help the body control pain. He said in animal models, an opioid antagonist may cause a resurgence of induced pain that had appeared to resolve.

“We have long-term mechanisms in our spinal cord and brain that control pain, and opioids may interfere with that,” he said.

Long-term opioid use also may increase a cancer survivor’s risk for mortality. According to Davis, patients who take 100 mg of morphine equivalent per day have a four to eight times higher risk for death. He said men who take long-term opioids may experience reductions in testosterone or hypogonadism, which can increase mortality risk. Sleep disordered breathing also may be worsened by opioids.

“During the day, people might look like they are perfectly fine,” he said. “However, they may have central sleep apnea or obstructive sleep apnea.”

Other potential risks include infection and wound dehiscence among women who have undergone gynecologic surgery, and pneumonia and ICU admission among patients with chronic obstructive lung disease, Davis said.

Opioid use in the year after completing active treatment has been linked to an immediate increased risk for serious adverse drug events related to opioid misuse, as well as other adverse events related to opioid use, he said (Davis et al.).

Opioid use by cancer type

The risk for inappropriate opioid use appears to vary by cancer type.

In a study of older survivors of breast, colorectal and prostate cancer, researchers found opioid overdose was a rare but statistically significant phenomenon among survivors of stage II to stage III colorectal cancer. Results showed colorectal cancer survivors had 2.3 times higher odds of opioid overdose than matched controls (adjusted OR = 2.33; 95% CI, 1.49-3.67).

“There have been a few studies, both from our group and others, that have shown differences in patterns of opioid use or opioid-related harms by cancer type,” Andrew W. Roberts, PharmD, PhD, first author of the study and assistant professor in the department of population health at University of Kansas School of Medicine, said. “In our study, the finding of some potential signal with opioid overdose risk in the colorectal cancer population is something we need to explore further.”

Roberts said although the reason for this apparent increased risk is not yet understood, it may be driven in part by the type and severity of pain experienced by this population.

“There are a lot of sources of pain [in colorectal cancer], and also the source of the pain can be experienced differently,” he told Healio. “Pain coming from your gut is different than surgical pain that is coming from a mastectomy, for example.”

Roberts added that previous studies have demonstrated mixed findings, suggesting an association between colorectal cancer and elevated risk for suicidal harm.

“This could be because the burden of treatment of the disease is different than that of other cancer types,” he said. “So, maybe what we’re seeing in part is the use of opioids as a sort of mechanism patients are using for self-harm, but we need to do a lot more work to substantiate that.”

Additionally, studies have suggested that lung and head and neck cancer survivors should be prioritized in efforts to improve opioid safety, since these patients may have a history of substance misuse.

“Individuals diagnosed with lung or head and neck cancers often have preexisting substance use going on, whether it’s smoking or alcohol use,” Roberts said. “So, it would make sense that you would see some increased risk for opioid-related harms in this population.”

‘An exit strategy’

According to Hashmi, a well-educated physician population is key to reducing opioid risks and harmful outcomes among cancer survivors. Whether the prescribing physician is an oncologist, a surgeon or a primary care provider, Hashmi said it is necessary to understand the complexities and nuances of pain.

“It is imperative that all clinicians dealing with [patients with cancer] have a deep understanding of all pain types and can differentiate between somatic vs. visceral vs. neuropathic pain syndromes,” he said. “Given that pain is an extremely common entity in most of our cancer survivors, we must evaluate and document the pain type, prior treatments, and short-and long-term plan, just as we do when staging cancers. This aspect of palliation is as important as the treatment of cancer itself.”

Davis said when discussing opioid treatment with a cancer survivor, it is important to clarify the finite nature of the regimen.

“If you are thinking of putting someone on [opioids], you ought to also have an exit strategy,” he said. “This discussion should occur when you’re starting opioid therapy, so that people understand it’s not an indefinite thing. I think that’s one part of the discussion on opioid therapy that has been largely missing.”

Hashmi added that if the clinician has carefully considered the patient’s potential risks for misuse and other risk factors, opioids should not be arbitrarily discontinued.

“As long as the physical issue is active, the treatments should be continued,” he said, “Otherwise, we have not done justice to the patient, and our understanding and efforts for pain management will be in vain.”

References:

For more information:

Rajesh Balkrishnan, PhD, can be reached at rb9ap@virginia.edu.

Mellar P. Davis, MD, FCCP, FAAHPM, can be reached at mdavis2@geisinger.edu.

Sharukh K. Hashmi, MD, is a member of the Navigating Survivorship Peer Perspective Board and can be reached at hashmi.shahrukh@mayo.edu.

Henry S. Park, MD, MPH, can be reached at henry.park@yale.edu.

Andrew W. Roberts, PharmD, PhD, can be reached at aroberts9@kumc.edu.