PURPOSE: Neuropathic pain is an unavoidable treatment-related adverse event among patients with head and neck cancer who are undergoing radiotherapy. We aimed to test the efficacy and safety of pregabalin versus placebo in the treatment of radiotherapy-related neuropathic pain.
PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled trial was conducted in four centers in China. Eligible patients with a mean pain intensity score of 4 or more on an 11-point numeric rating scale were randomly assigned to receive either active treatment with a flexible dose of pregabalin or placebo for 16 weeks. The primary efficacy outcome was pain reduction measured on the numeric rating scale.
RESULT: There were 128 patients who received treatment as randomly assigned. Pain intensity reduction was 2.44 in the pregabalin arm and 1.58 in the placebo arm at week 16, yielding an adjusted mean difference of 0.87 (95% CI, 0.30 to 1.44; P = .003). In the pregabalin arm, 38 patients (59.4%) achieved at least 30% pain relief versus 21 (32.8%) in the placebo arm ( P = .006). Nineteen patients (29.7%) in the pregabalin group and five (7.8%) in the placebo group achieved 50% or greater pain relief ( P = .003). Total scores on the Profile of Mood States-Short Form, pain severity and functional interference of Brief Pain Inventory-Short Form, as well as the physiology and psychology domain of the WHO Quality of Life-BREF all were reduced significantly at week 16 in patients who received pregabalin compared with those who received placebo. There was no significant difference ( P = .29) in the incidence of experiencing at least one adverse event in the pregabalin arm (n = 35; 54.7%) versus the placebo arm (n = 29; 45.3%).
CONCLUSION: Patients treated with pregabalin with radiotherapy-related neuropathic pain had greater pain alleviation, better mood states, and higher quality of life compared with patients in the placebo group, with a good tolerability.
This is an important randomized study, demonstrating the value of Pregabalin as treatment for long-term postradiation neuropathic pain. The patients were followed for 16 weeks, without evidence of lessening of effect. Postradiation pain is often persistent, once it occurs, and it will be important to determine whether the effect of Pregabalin is maintained, and/or patients develop side effects from long-term use of the drug.
This is an interesting and important article given the lack of high-quality data regarding the treatment of radiation-induced neuropathic pain. Despite this being a positive study, it is important to note that only 30% of patients in the prebalin group had a 50% reduction in pain. Also given the cost differential, it would have been nice to have data on gabapentin.
Management of neuropathic pain (NP), including treatment-related NP, in cancer patients is a complex task and a well-recognized unmet medical need. Strengths: patients were followed and evaluated over time by the Neuropathy Pain Scale after a careful NP diagnosis through a validated tool. The authors also followed the IMMPACT recommendations for chronic pain as they evaluated multiple outcome measures. Limitation: the authors did not emphasize well that over half the patients experienced at least one adverse effect.