Opioid Epidemic Poses Complex Problem for Cancer Care

Maurie Markman, MD

News reports of the opioid addiction epidemic are startling and profoundly distressing. The devastating impact of addiction on families and communities cannot be overstated or even fully comprehended. For example, more than 11 million Americans are inappropriately using opioids, according to a 2016 estimate.¹ Further, compared with 1999, the number of deaths related to opioids has increased more than 4-fold.¹ One estimate suggested that more than 90 Americans die every day from opioid overdoses.²

The cause, or more appropriately causes, of this massive societal problem are extensively debated. Although the extent of the dilemma mandates that the focus be on the rapid development and implementation of effective and workable solutions, much of the discussion continues to be political in nature, including attempts to find individuals or groups to blame. The “blame game” is not difficult to play in retrospect. Consider, for example, the laudable efforts of many, including the Joint Commission on Accreditation of Healthcare Organizations, to institute a clinically relevant focus on the successful management of pain for hospitalized patients as an indication of overall quality. It is reasonable to speculate that a substantial number of individuals who initiated opioids within the hospital environment, continued on discharge, and subsequently became addicted to narcotics received prescriptions from clinicians who were seeking to respond to patientreported complaints.³ There was never ill-intent here, only a most unfortunate lack of understanding of the distressing negative potential of such actions.

Then there is, in retrospect, the simply stunning assumption that addiction in the setting of routine medical care was unlikely to occur despite a lack of evidence supporting that belief. For example, 1 commonly cited source in this arena was simply a letter to the editor that contended—with a paucity of objective data to support its conclusions—that hospital patients treated with narcotics rarely developed addictions.³

Finally, one must acknowledge the absence of studies designed to determine the relative efficacy and toxicity (both short term and long term) of narcotic versus non-narcotic pain medications in a variety of common clinical settings. Many apparently assumed that in certain circumstances where pain was present an opioid would be considered the most appropriate first-line therapeutic option.

Recently reported phase III randomized trial data have provided striking evidence that certain beliefs are simply incorrect. For example, an evaluation of the use of an opioid versus a nonopioid strategy in the management of chronic back pain or hip/knee osteoarthritic pain over a 12-month period found the nonopioid approach resulted in both superior efficacy and reduced toxicity.⁴ Similarly, a study examining a single dose of a nonopioid versus an opioid medication employed in an emergency room for the management of acute extremity pain found no efficacy differences between the approaches.⁵

Of course, the use of opioids in the population of patients with cancer has long been recognized to be unique, playing an often essential role in palliative and end-of-life care. However, there also has been an apparent belief that patients with an advanced cancer have a low addiction risk potential, an assumption seriously challenged by recent evidence.⁶ In fact, oncology publications have begun to focus on the problem of individuals with cancer who exhibit behaviors suggesting addiction to pain medications.⁶

Further, provocative retrospective data have suggested that newly diagnosed patients with cancer receiving a relatively large dose of opioid medications (more than 5-mg oral morphine equivalents per day) consume more health-related resources and experience inferior overall survival compared with patients who receive fewer opioids.⁷ The investigators found this association to be relevant even after correcting for patient age, gender, and prognostic grouping. Of course, one must be very cautious in assuming there is a direct cause-and-effect relationship between the use of opioids and these specific outcomes as the administration of large quantities of narcotic medication may simply reflect the presence and appropriate management of a more advanced progressive malignancy. However, the potential for a direct impact of opioid use on the cost of cancer care and survival requires further examination.

Finally, recent data have revealed a similar concern with the potentially inappropriate use of narcotic pain medications in the setting of cancer surgery with curative intent, as has been observed in the noncancer setting.⁸ In an analysis of 68,463 such patients undergoing surgery between 2010 and 2014 who filled a prescription for an opioid medication, 10.4% of previously narcotic-naïve individuals continued to fill a prescription 90 to 180 days following surgery, a percentage similar to that of patients undergoing noncancer-related surgical procedures.⁸

Of note, the authors of this analysis concluded that 1 year after surgery patients with persistent narcotic use (as defined above) received daily doses equivalent to that of individuals classified as chronic opioid users. Further, individuals who received adjuvant chemotherapy following surgery were more likely to be persistent opioid users, suggesting narcotics were being utilized for the management of systemic therapy—related adverse effects, a questionable strategy that may result in a serious potential for subsequent addiction.

Although the continued use of opioid medications may have been appropriate for many of these patients on clinical grounds, the magnitude of persistent use is concerning and efforts to minimize— or completely avoid—wherever possible the administration of narcotics should be appropriately encouraged.

References

1. Blendon RJ, Benson JM. The public and the opioid-abuse epidemic. N Engl J Med. 2018; 378(5):407-411. doi: 10.1056/NEJMp1714529.
2. Volkow ND, Collins FS. The role of science in addressing the opioid crisis. N Engl J Med. 2017;377(4):391-394. doi: 10.1056/NEJMsr1706626.
3. Baker DW. History of The Joint Commission’s pain standards: lessons for today’s prescription opioid epidemic. JAMA. 2017;317(11):1117-1118. doi: 10.1001/jama.2017.0935.
4. Krebs EE, Gravely A, Nugent S, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: the SPACE randomized clinical trial. JAMA. 2018;319(9):872-882. doi: 10.1001/jama.2018.0899.
5. Chang AK, Bijur PE, Esses D, Barnaby DP, Baer J. Effect of a single dose of oral opioid and nonopioid analgesics on acute extremity pain in the emergency department. JAMA. 2017; 318(17):1661-1667. doi: 10.1001/jama.2017.16190.
6. Arthur J, Edwards T, Reddy S, et al. Outcomes of a specialized interdisciplinary approach for patients with cancer with aberrant opioid-related behavior. Oncologist. 2018;23(2):263-270. doi: 10.1634/theoncologist.2017-0248.
7. Zylla D, Steele G, Shapiro A, Richter S, Gupta P. Impact of opioid use on health care utilization and survival in patients with newly diagnosed stage IV malignancies [published online February 2, 2018]. Support Care Cancer. doi: 10.1007/s00520-018-4062-z.
8. Lee JS, Hu HM, Edelman AL, et al. New persistent opioid use among patients with cancer after curative-intent surgery. J Clin Oncol. 2017;35(36):4042- 4049. doi: 10.1200/JCO.2017.74.1363.