Investigators have uncovered concerningly large gaps in evidence regarding the true benefits of opioids for pain relief in patients with cancer, according to a novel study published by Shaheed et al in CA: A Cancer Journal for Clinicians. The new findings could challenge the commonly held view that opioids are the most powerful pain relievers.
Morphine is often considered the standard treatment option for moderate to severe cancer pain because of its low cost and accessibility. Although many international guidelines such as those of the World Health Organization (WHO) currently recommend opioids—the most common treatment to manage background cancer pain (constant pain) and breakthrough cancer pain (temporary flare-ups in addition to background pain)—few studies have compared commonly used opioids like morphine, oxycodone, and methadone with placebo in this patient population.
Study Methods and Results
In the new study, the investigators examined the data of over 150 clinical trials involving patients treated with opioids for cancer pain. Among the placebo-controlled trials, the investigators found evidence of moderate certainty that tapentadol may be more effective than placebo at treating background pain. Opioids commonly thought of as weaker such as codeine; nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, piroxicam, ketorolac, and diclofenac; and the antidepressant imipramine may be just as effective at treating background pain, but with fewer side effects.
For breakthrough cancer pain, the investigators discovered that fentanyl administered as a nasal spray, under the tongue, between the gum and cheek, or as an oral spray may be more effective than placebo. However, the findings were not applicable to the regular use of fentanyl, and patients who received the drug experienced more side effects than those who received placebo.
The investigators noted that they did not find convincing evidence that morphine was better or safer than other opioids for background cancer pain outside of end-of-life care. Additionally, morphine and other opioids were found to potentially affect the body’s ability to fight cancer. Nonetheless, more research may be needed to determine whether there are negative interactions between opioids and cancer therapy or the immune system to ensure that pain management does not negatively impact survival.
Conclusions
“The lack of evidence comparing opioids to placebo for cancer pain probably reflects the ethical and logistical challenges associated with carrying out such trials. Yet, these trials are necessary to guide clinical decision-making,” explained lead study author Christina Abdel Shaheed, PhD, Faculty of Medicine and Health as well as Sydney Musculoskeletal Health at the University of Sydney School of Public Health.
The investigators noted that the results from their study suggested there may be no “one-size-fits-all” approach to treating cancer pain—urging health-care professionals and patients to carefully weigh new evidence during the decision-making process for pain management. Despite being indispensable for intractable pain and distress in end-of-life care, nonopioids, particularly NSAIDs, may be effective for some cancer pain and may help avoid issues like dependency and waning opioid analgesia over time. The investigators indicated that patients with background pain may have an improved quality of life with less focus on opioids.
“The hope is that the findings can help guide [physicians] and patients to choose between different opioid treatments for cancer pain and empower [patients] to consider alternatives if they are unable to tolerate opioid medicines or choose not to take them,” concluded senior study author Mark Sidhom, MBBS, of the Cancer Therapy Centre at the Liverpool Hospital in Australia.
Disclosure: For full disclosures of the study authors, visit acsjournals.onlinelibrary.wiley.com.
