Nonopioids as Effective as Opioids for Some Cancer Patients

In some cases, nonopioid analgesics and nonsteroidal anti-inﬂammatory drugs (NSAIDs) may be as effective as opioids in managing chronic cancer pain, according to the findings of a new meta-analysis.

The review examined the effectiveness of several therapeutic classes of drugs and individual treatments of chronic cancer pain in a total of 10,003 patients with cancer who participated in 81 randomized clinical trials.

With respect to global efficacy, nonopioid analgesics, NSAIDs, and opioids were the most effective classes. For individual treatments, the nonopioid analgesic lidocaine (multiple brands), the opioid-NSAID combination therapy of codeine plus aspirin, and the antiepileptic pregabalin (Lyrica, PF Prism CV) appeared to offer the most relief.

No medication class significantly improved pain intensity as compared with placebo, but the nonopioid analgesic ziconotide (Prialt, TerSera Therapeutics), the opioid dezocine (Dalgan, AstraZeneca), and the NSAID diclofenac (multiple brands) were the most effective individual treatments.

The meta-analysis was published online April 2 in the Journal of Clinical Oncology.

In light of concern over the opioid epidemic and the passage of legislation to curtail unnecessary opioid use, oncologists and cancer patients have expressed fear that access to adequate pain relief could be restricted. However, in an unusual move, the Centers for Disease Control and Prevention (CDC) recently issued a clarification letter to reassure the cancer community that appropriate pain medication will not be denied to them. The CDC stated, "The agency does not want to deny clinically appropriate opioid therapy to cancer and sickle cell disease patients, particularly those who are undergoing cancer treatment and survivors with chronic pain."

Do All Cancer Patients Need Opioids?

The study authors, led by Rongzhong Huang, PhD, of the First People's Hospital of Yunnan Province, Kunming, People's Republic of China, conclude that their evidence indicates that there are significant differences in efficacy in the current regimens used to treat chronic cancer pain.

"Our evidence also suggests that certain nonopioid analgesics and NSAIDs can serve as effectively as opioid therapy in managing chronic cancer pain," they write.

However, in an accompanying editorial, Ellen M. Lavoie Smith, PhD, of the University of Michigan School of Nursing, Ann Arbor, cautions that although it is "important to identify effective and safe nonopioid treatments for cancer pain, avoiding opioids altogether may not be in the best interest of every patient."

Avoiding opioids altogether may not be in the best interest of every patient. Dr Ellen Lavoie Smith

More research is needed to develop "innovative, patient centric, multidimensional solutions that target numerous biopsychosocial factors," she suggests. In addition, incorporating the common sense clinical practice of efﬁcacy, feasibility, and risk avoidance "will protect us from misinterpreting high-level scientiﬁc evidence that could lead us down the wrong path.

"Future collaboration among diverse stakeholders (eg, patients, clinicians, scientists, policymakers) will be important as we strive to ﬁnd mechanism-targeted approaches, identify and manage high-risk populations, and enforce principle-based policies that maximize the safety, comfort, and quality of life of people with cancer," Smith writes.

Varied Efficacy Among Drug Classes

Opioids remain the primary choice for managing chronic cancer pain, the authors note. At the same time, various nonopioid agents are currently being prescribed, although few studies have compared efficacy. Huang and colleagues conducted a meta-analysis of randomized controlled trials that compared any systemic pharmaceutical intervention or combination used in treating patients with chronic cancer pain. The primary outcome was global efficacy, reported as an odds ratio (OR). A secondary endpoint was change in pain intensity, reported as a standardized mean difference.

The investigators found that nonopioid analgesics (network OR, 0.30; 95% credibility interval [CrI], 0.13 – 0.67), NSAIDs (network OR, 0.44; 95% CrI, 0.22 – 0.90), and opioids (network OR, 0.49; 95% CrI, 0.27 – 0.86) were significantly superior in global efficacy in comparison to placebo.

Surface under the cumulative ranking curve analysis (SUCRA) was used to rank each medication class according to its global efficacy. The top-ranked classes for global efficacy were nonopioid analgesics (SUCRA score, 76.3), NSAIDs (SUCRA score, 55.9), and opioids (class O; SUCRA score, 49.7).

Regarding individual treatments, pooled network OR values showed that lidocaine (network OR, 0.04; 95% CrI, 0.01 – 0.18), codeine plus aspirin (network OR, 0.22; 95% CrI, 0.08 – 0.63), pregabalin (network OR, 0.29; 95% CrI, 0.08 – 0.92), ketorolac tromethamine (multiple brands) (network OR, 0.29; 95% CrI, 0.08 – 0.99), and ketoprofen (multiple brands) (network OR, 0.32; 95% CrI, 0.10 – 0.97) were significantly superior in global efficacy compared to placebo. The top-ranked interventions for global efficacy were lidocaine (SUCRA score, 98.1), codeine plus aspirin (SUCRA score, 81.1), and pregabalin (SUCRA score, 73.8).

The authors assessed pain intensity with each medication class and for individual intervention. A pairwise meta-analysis that compared each class against placebo showed that none were significantly superior to placebo. Although all were equivalent to placebo, the top-ranked classes for reducing pain intensity were nonopioid analgesics (class A; SUCRA score, 78.2), NSAIDs (class N; SUCRA score, 72.8), and antidepressants (class D; SUCRA score, 52.0).

For individual intervention, the top-ranked interventions were nonopioid analgesics (SUCRA score, 78.2), NSAIDs (SUCRA score, 72.8), and antidepressants (SUCRA score, 52.0).

"To our knowledge, this is the first network meta-analysis to comparatively evaluate the effectiveness of various therapeutic regimens for chronic cancer pain," they write. "Our findings indicate that there are significant differences in efficacy among current therapeutic regimens for chronic cancer pain."

The study was supported by grants from the National Natural Science Foundation of China and the Special Foundation for Science and Technology Development of Anhui Province. The authors have disclosed no relevant financial relationships. Smith has a consulting/advisory role for Mundipharma and Disarm Therapeutics and has received institutional research funding from the National Institutes of Health/National Cancer Institute.

J Clin Oncol. Published online April 2, 2019. Full text

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