Dexamethasone for the Prevention of a Pain Flare After Palliative Radiation Therapy for Painful Bone Metastases: The Multicenter Double-Blind Placebo-Controlled 3-Armed Randomized Dutch DEXA Study

Int J Radiat Oncol Biol Phys. 2020 Nov 1;108(3):546-553. doi: 10.1016/j.ijrobp.2020.05.007. Epub 2020 May 22.

Abstract

Purpose: After radiation therapy for painful bone metastases, up to 44% of patients report a pain flare (PF). Our study compared 2 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 8 mg dexamethasone before radiation therapy followed by 3 daily doses (group A), 8 mg dexamethasone followed by 3 doses of placebo (group B), or 4 doses of placebo (group C). 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 2-point increase on a 0 to 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 lower. The primary analysis was by intention to treat with patients who had missing data classified as having a PF.

Results: From January 2012 to April 2016, 295 patients were randomized. PF incidence was 38% for group A, 27% for group B, and 39% for group C (P = .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 group A, 4.5 days for group B, and 3.3 days for group C (P = .0567). Dexamethasone postponed PF occurrence; in group A 52% occurred on days 2 to 5 versus 73% in group B and 99% in group C (P = .02). Patients in group A reported lower mean pain scores on days 2 to 5 than those in group B or C (P < .001). Side effects were similar.

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 days 2 to 5.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Bone Neoplasms / radiotherapy*
  • Bone Neoplasms / secondary
  • Cancer Pain / drug therapy
  • Cancer Pain / epidemiology
  • Cancer Pain / prevention & control*
  • Dexamethasone / administration & dosage*
  • Disease Progression
  • Double-Blind Method
  • Female
  • Glucocorticoids / administration & dosage*
  • Humans
  • Intention to Treat Analysis
  • Male
  • Middle Aged
  • Netherlands
  • Outcome Assessment, Health Care
  • Pain Measurement
  • Palliative Care / methods
  • Placebos / administration & dosage
  • Symptom Flare Up*
  • Time Factors

Substances

  • Analgesics, Opioid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Glucocorticoids
  • Placebos
  • Dexamethasone