Adjusted Indirect and Mixed Comparisons of Drug Therapy for Neuropathic Cancer Pain

Treatments for neuropathic cancer pain (NCP) are often based on guidelines or treatment data for neuropathic pain of noncancer origin. Therefore, their relative efficacy and safety are not well characterized and should be determined. This study aimed to compare the efficacy and safety of various pharmacological interventions for NCP.

We systematically searched PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for relevant randomized controlled trials (RCTs) from inception to June 13, 2024; 36 studies were included. The primary outcome was pain intensity; secondary outcomes included the effective pain relief rate, nausea and vomiting, and overall adverse events. The certainty of evidence was assessed using the CINeMA web application.

The combination of opioids, antiepileptics, and nonsteroidal anti-inflammatory drugs (NSAIDs) appeared to be the most effective treatment to reduce pain intensity (surface under the cumulative ranking [SUCRA] curve: 0.91), followed by the combination of antiepileptics and antidepressants (SUCRA: 0.90). For secondary outcomes, the combination of opioids and neurotropin was associated with the highest probability of achieving the best pain relief rate (SUCRA: 0.81), whereas vitamin B12 appeared to be relatively ineffective. Regarding safety, vitamin B12 was associated with the highest probability of being the safest treatment for nausea and vomiting (SUCRA: 0.90), followed by antiepileptic drugs (SUCRA: 0.87). For overall adverse events, antidepressants were associated with the highest probability of being the safest treatment (SUCRA: 0.86). For the primary outcome, 84.8% of the comparisons were rated as being of low or very low confidence according to the CINeMA method.

Antiepileptics and antidepressants, alone or in combination, and certain opioid-based combinations may be effective for NCP based on current evidence, although the certainty of this evidence is low. Some plant-derived compounds also demonstrated potential analgesic effects, although these findings are exploratory and based on a limited number of trials, and further evidence is needed to verify their efficacy. Given the low certainty of most comparisons, clinicians should interpret these results cautiously and balance potential benefits with safety profiles when selecting treatments for NCP.