Randomized Study of Pregabalin in Patients with Cancer-Induced Bone Pain

Abstract

IntroductionImprovements are needed in the management of cancer-induced bone pain (CIBP). The objective of this study was to assess the efficacy and safety of pregabalin compared with placebo in the adjunctive treatment of patients with moderate to severe CIBP who were receiving opioids.MethodsIn this randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, 152 adults diagnosed with a malignant, solid tumor with metastases to bone were randomized to flexible-dose pregabalin (100, 150, 300, or 600 mg/day) or placebo, as add-on to stable opioid analgesic therapy, which was optimized prior to the start of the study. The primary efficacy endpoint was the duration-adjusted average change (DAAC) from baseline in the daily worst pain at the reference site (measured by 11-point numeric rating scale [NRS]) during the fixed-dosage phase. The study was terminated early following an interim analysis that indicated an increase in sample size would be needed to satisfy statistical assumptions for the primary endpoint. Given the early termination of the study, only descriptive analyses were performed.ResultsThe mean (standard deviation) DAAC from baseline in NRS score for the primary endpoint favored pregabalin treatment: −1.53 (1.81) in the pregabalin group and −1.23 (1.74) in the placebo group. Mean DAAC for average pain and sleep interference (NRS) also favored pregabalin. More patients treated with pregabalin reported improvement (“very much improved,” “much improved,” or “minimally improved”) based on Patient Global Impression of Change: 81.4% compared with 70.0% in the placebo group.ConclusionData from this study indicate that pregabalin use may reduce metastatic bone pain. Due to the incomplete analysis, further study of pregabalin in the management of CIBP is required.

Randomized Double-Blind Trial of Pregabalin Versus Placebo in Conjunction With Palliative Radiotherapy for Cancer-Induced Bone Pain

“…14 It was followed by a randomized trial of pregabalin versus placebo, which suggested potential value of pregabalin in CIBP, although firm conclusions could not be drawn. 15 Another study suggested pregabalin in combination with mirtazapine may be beneficial; however, it advised additional trials. 16 Nevertheless, despite the limited evidence, pregabalin is often prescribed for CIBP, with some reviews of CIBP management recommending the use of pregabalin if there is a neuropathic component to the pain.…”

Pharmacological Treatment of Pain in Cancer Patients: The Role of Adjuvant Analgesics, a Systematic Review

“…One RCT that compared the efficacy of pregabalin vs. placebo in patients with metastatic bone pain was aborted because of slow inclusion. The pain in the pregabalin group seemed to decrease more than in the placebo group.…”

“…Adjuvant analgesics in the treatment of cancer pain are usually, but not exclusively, used for the treatment of purely neuropathic or mixed cancer pain. Anticonvulsants and antidepressants are increasingly used for pain due to bone metastases, and NMDA receptor antagonists are mainly used when other therapies fail …”

Gabapentin as an Adjuvant Therapy for Prevention of Acute Phantom-Limb Pain in Pediatric Patients Undergoing Amputation for Malignant Bone Tumors: A Prospective Double-Blind Randomized Controlled Trial

“…8 Gabapentin is also known to increase the serotonin concentration in human blood, which may be linked to its neurobehavioral actions. 14 Krane and Heller 4 observed the natural history of PLP in pediatric patients who underwent amputation and found that both frequency and intensity of PLP were decreased within six months after amputation, and the rate of PLP remained unchanged significantly after six months to seven years. For patients who did not develop postoperative PLP, gabapentin can be discontinued six weeks after amputation.…”