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Opioids vs the Rest for Chronic Cancer Pain

Certain non-opioid analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) may help relieve chronic cancer pain as effectively as opioids and are not associated with any addiction risk, a network meta-analysis done by Chinese investigators found.

Having analyzed 81 randomized controlled trials (RCTs) involving 10,000 patients, the most effective drug classes compared with placebo for the primary outcome of global efficacy were non-opioid analgesics such as acetaminophen, followed by NSAIDs and then opioids, according to Xiaojing Wang, PhD, of Bengbu Medical College in China, and colleagues.

The most effective individual drugs were the non-opioid lidocaine, the opioid-NSAID combination of codeine plus aspirin, and the antiepileptic pregabalin (Lyrica), the study in the Journal of Clinical Oncology reported.

No medication class was superior to placebo for the secondary endpoint of reducing pain intensity on a standardized pain scale. The most effective individual treatments were intrathecal ziconotide (Prialt), the partial opioid dezocine (Dalgan), and the NSAID diclofenac (Voltaren).

“To our knowledge, this is the first network meta-analysis to comparatively evaluate the effectiveness of various therapeutic regimens for chronic cancer pain,” Wang’s group wrote. “In contrast to commonly held beliefs regarding the superiority of opioids as the mainstay of cancer pain therapy, our evidence suggests that certain non-opioid analgesics and NSAIDs can serve as effectively as opioid therapy in managing chronic cancer pain.”

In an accompanying editorial, however, Ellen Lavoie Smith, PhD, of the University of Michigan School of Nursing in Ann Arbor, questioned the legitimacy of some of the RCTs included in the meta-analysis. For example, the authors’ finding that lidocaine, typically administered topically, was the most effective drug for improving global efficacy, based on two small studies in which researchers tested intravenous lidocaine in patients with neuropathic and opioid-refractory pain.

Similarly, the suggestion that ziconotide and dezocine are two of the best drugs for treating chronic cancer pain was based on older studies: a 15-year old trial in the case of ziconotide (given intrathecally) and a 30-year-old trial in the case of dezocine (given intramuscularly).

“Results from such outdated, single studies should not serve as the foundation for modern clinical practice recommendations,” Lavoie Smith argued.

Furthermore, physicians have to consider the inconvenience of having to administer any drug intravenously, intrathecally, or intramuscularly, especially if symptoms have palliated over an extended period of time.

“For patients in home and hospice settings, drugs administered through oral, intransal, rectal, sublingual, and transdermal routes are preferred because they are easy to self-administer, are noninvasive, and do not necessitate ongoing professional infusion services,” Lavoie Smith emphasized. “Attention to the triad of common sense clinical practice — efficacy, feasibility, and risk avoidance — will protect us from misinterpreting high-level scientific evidence that could lead us down the wrong path.”

For the study, investigators defined global efficacy as treatment success versus failure compared with placebo. By medication class, pooled network ORs were 0.30 (95% CI 0.13-0.67) for the non-opioid analgesics, 0.44 (95% CI 0.22-0.90) for the NSAIDs, and 0.49 (95% CI 0.27-0.86) for the opioids.

By individual drug treatment, ORs were 0.04 (95% CI 0.01-0.18) for lidocaine, 0.22 (95% CI 0.08-0.63) for codeine plus aspirin, and 0.29 (95% CI 0.08-0.92) for pregabalin versus placebo.

For the secondary endpoint of reducing pain intensity, “no class was superior to placebo,” on a standardized 100-point pain scale, the investigators stressed. However, individual drugs were shown to be superior to placebo. The standardized mean differences (SMDs) between active and placebo controls were -24.98 (95% CI -32.62 to -17.35) for ziconotide, followed by -13.56 (95% CI -23.37 to -3.69) for dezocine and -11.22 (95% CI -15.91 to -5.80) for diclofenac.

“Chronic cancer pain is one of the most prevalent symptoms affecting patients with cancer, with greater than one-third of patients with cancer rating their pain as moderate to severe in nature,” researchers wrote. “Our findings indicate that there are significant differences in efficacy among current therapeutic regimens for chronic cancer pain.”

Study authors had no conflicts of interest to declare.

Lavoie Smith reported serving as a consultant or advisor to Mundipharma Research and Disarm Therapeutics.

Source: MedicalNewsToday.com