Yvette M van der Linden1, Paulien G Westhoff2, Rebecca K Stellato3, Angela van Baardwijk4, Kim de Vries5, Francisca Ong6, Ruud Wiggenraad7, Bonnie Bakri8, Gerda Wester9, Ilse de Pree10, Lieneke van Veelen11, Tom Budiharto12, Maaike Schippers13, Anna K L Reyners14, Alexander de Graeff15. 1. Department of Radiotherapy, Leiden University Medical Centre, Leiden, the Netherlands; Centre of Expertise in Palliative Care, Leiden University Medical Centre, Leiden, the Netherlands. Electronic address: ymvanderlinden@lumc.nl. 2. Department of Radiotherapy, University Medical Centre Utrecht, Utrecht, the Netherlands; Department of Radiotherapy, Radboud University Medical Centre, Nijmegen, the Netherlands. 3. Department of Biostatistics, Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands. 4. MAASTRO, Maastricht, the Netherlands. 5. Department of Radiotherapy, National Cancer Institute, Amsterdam, the Netherlands; Department of Radiotherapy, Erasmus Medical Centre, Rotterdam, the Netherlands. 6. Department of Radiotherapy, Medical Spectrum Twente, Enschede, the Netherlands. 7. Department of Radiotherapy, Haaglanden Medical Centre, The Hague, the Netherlands. 8. Department of Radiotherapy, Reinier de Graaf Hospital, Delft, the Netherlands. 9. Radiotherapy Group Arnhem, Arnhem, the Netherlands. 10. Department of Radiotherapy, Erasmus Medical Centre, Rotterdam, the Netherlands. 11. ZRTI, Vlissingen, the Netherlands. 12. Department of Radiotherapy, Catharina Hospital, Eindhoven, the Netherlands. 13. Bernard Verbeeten Institute, Tilburg, the Netherlands. 14. Department of Medical Oncology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands. 15. Department of Medical Oncology, University Medical Centre Utrecht, Utrecht, the Netherlands.
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.
RCT Entities:
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.