Dexamethasone for the prevention of a pain flare after palliative radiotherapy for painful bone metastases: the multicenter double-blind placebo-controlled three-armed randomized Dutch DEXA study.

Abstract Purpose After radiotherapy for painful bone metastases up to 44% of patients report a pain flare (PF). Our study compared two dose schedules of dexamethasone versus placebo to prevent PF. Methods and materials This double-blind, randomized, placebo-controlled trial allocated patients with painful bone metastases from solid tumors randomly to receive A: 8 mg dexamethasone before radiotherapy, followed by three daily doses, B: 8 mg dexamethasone followed by three doses of placebo, or C: four doses of placebo. Patients reported worst pain scores, study medication side effects and opioid intake before treatment and thereafter daily for 14 days and on day 28. PF was defined as at least a two-point increase on a 0-10 pain scale with no decrease in opioid intake, or a 25% or greater increase in opioid intake with no decrease in pain score, followed by a return to baseline or below. The primary analysis was by intention-to-treat with patients with missing data classified as having a PF. Results From January 2012 to April 2016, 295 patients were randomized. PF incidence was 38% for A, 27% for B, and 39% for C (p= 0.07). Although patients in group B had the lowest PF-incidence, a relatively high percentage did not return to baseline pain levels indicating pain progression. The mean duration of PF was 2.1 days for A, 4.5 days for B and 3.3 days for C (p= 0.0567). Dexamethasone postponed PF occurrence: in A, 52% occurred on day 2-5 vs. 73% in B and 99% in C (p=0.02). Patients in group A reported lower mean pain scores on days 2-5 than in B or C (p Conclusions There was insufficient evidence that dexamethasone reduced the incidence of radiation-induced PF. However, dexamethasone postponed the occurrence of PF and led to lower mean pain scores on day 2-5.