Underprescription of Opioids in Cancer Patients During End of Life

Researchers have provided the first detailed analysis of the relatively late onset and short duration of strong opioid treatment in cancer patients before death, lending support to the hypothesis that — despite opioid prescribing increasing exponentially for other types of pain, raising concerns of an international opioid prescribing epidemic — cancer-related pain is being undertreated.¹

“For patients with cancer, opioid prescribing has not increased to the same extent and still represents only 16.1% of all opioid prescriptions issued in the United Kingdom,” wrote Lucy Ziegler, PhD, from the University of Leeds, UK and colleagues, citing National Health Service data.² “Our [study] data suggest that many more patients with advanced cancer and pain may benefit from a strong opioid analgesic.”

Dr Ziegler and colleagues linked UK cancer registry data with corresponding electronic primary care records of 6080 patients who died of cancer over a 7-year period (2005-2012) in Leeds, the third largest city in the United Kingdom. The cohort was deemed to be representative of all UK cancer patients in terms of cancer prevalence and mortality.

Patients in the cohort were stratified into 3 analgesic groups: those who received no analgesics; those who received at least 1 prescription for nonopioids/weak opioids, but no strong opioids; and those who received at least 1 prescription for a strong opioid.

The group that received a strong opioid was further divided into early receivers (given ≥10 weeks before death) and late receivers (given ≤9 weeks before death) to determine factors affecting prescription timing.  

“This study is the first to accurately determine the median interval between first prescription of a strong opioid and death in a large population by charting analgesic prescribing daily over the last year of life,” the authors wrote. “[It is also] the first study to explore the relationship between opioid prescribing for cancer pain in relation to place of death.”

Among the cohort, 1470 patients had received no analgesics and the remaining 4610 cumulatively received 96 810 analgesic prescriptions, with 31.5% being for nonopioids, 25.2% being for weak opioids, and 43.3% being for strong opioids. Approximately 48% of patients received at least 1 prescription for a strong opioid, but only 30% received a strong opioid at 6 weeks before death. When examining opioid prescriptions, the investigators found 36.7% were for morphine, 15.9% for diamorphine, 11.2% for oxycodone, 10.4% for fentanyl, 3.7% for buprenorphine, and 0.3% for other agents.

Patients who died in the hospital versus in a hospice setting were 60% less likely to receive a strong opioid in the community in the last year of life (relative risk ratio [RRR], 0.4; 95% confidence interval [CI], 0.3-0.5; P <.001), whereas patients who received chemotherapy in the last year of life were 30% more likely to receive a strong opioid than those who did not receive chemotherapy (RRR, 1.3; 95% CI, 1.1-1.6; P value was not specified).

When examining factors associated with timing and duration of strong opioid prescriptions, the authors found the median interval between first prescription for any strong opioid and death to be 9 weeks (range, 3-23 weeks). Diamorphine was the opioid prescribed closest to death, with a median interval before death of 1 week (range, 1-3 weeks). “[This] is consistent with its typical clinical use in the United Kingdom as a subcutaneous infusion in the last days of life,” the authors wrote.

Factors associated with being a late receiver of a strong opioid included age >60 years versus age <50 years, dying in a hospital versus dying at home or a care home, and having surgery. In contrast, patients who received chemotherapy or radiotherapy were 30% more likely to receive an early prescription for a strong opioid. Cancer site and patient sex did not appear to significantly affect strong opioid prescribing or timing.

Summary & Clinical Applicability

“The clinical implications of this study are clear; within the advanced cancer population, there is a need to develop mechanisms to improve pain assessment and initiate a more proactive approach to prescribing, particularly for older patients,” the authors wrote. “One mechanism to achieve this is through earlier integration of palliative care to improve pain control and begin to address the inequalities evidenced here,” they concluded.