Background Managing cancer-induced bone pain (CIBP) is challenging as background pain combined with more severe incident pain on movement makes balancing analgesia and side effects difficult. Pregabalin and gabapentin are indicated for neuropathic pain and pre-clinical studies suggest these drugs could modulate CIBP.
Aim To examine the effectiveness of pregabalin and gabapentin for management of CIBP.
Methods A systematic review of clinical trials investigating pregabalin or gabapentin as the intervention for CIBP, with change or reduction in pain scores as outcome. Embase, Medline, Cinahl and Cochrane databases were searched from inception to March 2016. Grey literature, reference lists, conference abstracts, and hand searching of key journals were undertaken.
Results Five of 35 screened studies met inclusion criteria. Pregabalin was investigated in three RCTs, and gabapentin in one RCT and one case series, including a total of 458 patients. All studies used numerical rating scales to assess worst or average pain over 5 days-4 weeks following pregabalin or gabapentin introduction. Two pregabalin versus placebo RCTs were methodologically strong and of these the largest and highest quality RCT showed no differences in average worst pain scores. The other RCT terminated early due to slow recruitment hence was underpowered, but indicated a small trend favouring pregabalin. A further pregabalin RCT showed significant reduction in pain scores but had methodological limitations. There was no difference in pain scores in the gabapentin versus placebo RCT, whereas the gabapentin case series reported six patients whose pain scores improved. Both gabapentin studies had design weaknesses. The drugs were well tolerated. Data heterogeneity meant meta-analysis was not possible.
Conclusion The strongest evidence to date suggests lack of effectiveness of pregabalin for CIBP. Future well conducted trials should incorporate subgroup analysis of differing primary tumour types and metastases location when evaluating these neuropathic agents in CIBP.
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