Dexamethasone for the prevention of a pain flare after palliative radiotherapy for painful bone metastases: a multicenter double-blind placebo-controlled randomized trial.

Paulien G Westhoff,Jenske I Geerling,Alexander De Graeff,Yvette M Van Der Linden,Anna Kl Reyners

doi:10.1186/1471-2407-14-347

Abstract

BackgroundRadiotherapy has a good effect in palliation of painful bone metastases, with a pain response rate of more than 60%. However, shortly after treatment, in approximately 40% of patients a temporary pain flare occurs, which is defined as a two-point increase of the worst pain score on an 11-point rating scale compared to baseline, without a decrease in analgesic intake, or a 25% increase in analgesic intake without a decrease in worst pain score, compared to baseline. A pain flare has a negative impact on daily functioning and mood of patients. It is thought to be caused by periostial edema after radiotherapy. Dexamethasone might diminish this edema and thereby reduce the incidence of pain flare. Two non-randomized studies suggest that dexamethasone reduces the incidence of a pain flare by 50%. The aim of this trial is to study the effectiveness of dexamethasone to prevent a pain flare after palliative radiotherapy for painful bone metastases and to determine the optimal dose schedule.Methods and designThis study is a three-armed, double-blind, placebo-controlled multicenter trial. We aim to include 411 patients with uncomplicated painful bone metastases from any type of primary solid tumor who receive short schedule radiotherapy (all conventional treatment schedules from one to six fractions). Arm 1 consists of daily placebo for four days, arm 2 starts with 8 mg dexamethasone before the (first) radiotherapy and three days placebo thereafter. Arm 3 consists of four days 8 mg dexamethasone. The primary endpoint is the occurrence of a pain flare. Secondary endpoints are pain, quality of life and side-effects of dexamethasone versus placebo. Patients complete a questionnaire (Brief Pain Inventory with two added questions about side-effects of medication, the EORTC QLQ-C15-PAL and QLQ-BM22 for quality of life) at baseline, daily for two weeks and lastly at four weeks.DiscussionThis study will show whether dexamethasone is effective in preventing a pain flare after palliative radiotherapy for painful bone metastases and, if so, to determine the optimal dose.Trial registrationThis study is registered at ClinicalTrials.gov: NCT01669499

Highlights

This study will show whether dexamethasone is effective in preventing a pain flare after palliative radiotherapy for painful bone metastases and, if so, to determine the optimal dose
Earlier publications suggest an effect of dexamethasone on the incidence of pain flare [6,7]
Side-effects of a short course and relative low dosage of dexamethasone are considered minimal, the beneficial effect in this patient population should be proven before integrating dexamethasone medication into daily clinical radiotherapy practice

Summary

Introduction

Radiotherapy has a good effect in palliation of painful bone metastases, with a pain response rate of more than 60%. Two non-randomized studies suggest that dexamethasone reduces the incidence of a pain flare by 50% The aim of this trial is to study the effectiveness of dexamethasone to prevent a pain flare after palliative radiotherapy for painful bone metastases and to determine the optimal dose schedule. Radiotherapy, with a single fraction of 8 Gray as the gold standard, has a good effect in palliation of painful bone metastases, with a pain response rate of more than 60%. Hird studied 111 patients with uncomplicated painful bone metastases and showed an incidence of pain flare of 40%, with no difference between single or multiple fractions. Loblaw studied 44 patients and found, with an adjusted, underestimating definition of a pain flare, an incidence of 41%, with a significant difference between single and multiple fractions (57% and 24% respectively) [4]

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