SAN ANTONIO—A five-day course of dexamethasone reduced radiation-induced pain flare from 35 percent to 26 percent among patients who had received palliative radiotherapy for bone metastases, according to a placebo-controlled, randomized, multi-institutional study presented here at the American Society for Radiation Oncology Annual Meeting (Abstract LBA 1).
In the National Cancer Institute of Canada Clinical Trials Group study, which was funded by the Canadian Cancer Society Research Institute, patients in the dexamethasone arm also had improvement in function and appetite and decreased nausea.
Pain flare was defined as at least a two-point increase in patient-rated worst pain on a scale of 0 to 10, with no decrease in analgesic intake; or a 25 percent or greater increase in analgesic intake with no decrease in the worst pain score from days zero to 10.
As explained by the principal investigator, Edward Chow, MBBS, PhD, Professor in the Department of Radiation Oncology at the University of Toronto and Chair of the Rapid Response Radiotherapy Program and Bone Metastases Site Group at Sunnybrook Health Sciences Centre in Toronto, the 298 patients enrolled from 23 centers throughout Canada received a single 8 Gy fraction of radiotherapy to one or two bone metastases, and were randomly assigned to receive 8 mg of oral dexamethasone daily for five days beginning on the first day of radiation (148 patients) or an oral placebo (150).
Patients reported their worst pain scores before radiotherapy and daily for 10 days after. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) C15-PAL, the EORTC-QLQ BM22 (both), and the Dexamethasone Symptom Questionnaire at baseline and at 10 and 42 days after treatment.
The questionnaire completion rate was 99 percent for the baseline questionnaire and 82 percent for the ones completed at days 10 and 42. The intention-to-treat analysis showed that 39 of 148 patients (26%) in the dexamethasone group had a pain flare, compared with 53 of 150 patients (35%) in the placebo group.
In the sensitivity analysis, which treated those with missing data as not evaluable, pain flare occurred in 26 patients (18%) who received dexamethasone, compared with 44 patients (29%) on placebo.
Also, at 10 days after treatment, patients in the dexamethasone arm were statistically significantly improved compared with patients in the placebo arm for nausea relief, interference with daily functioning, and appetite, compared with baseline.
There were two grade 3 and one grade 4 biochemical hyperglycemic events in the dexamethasone group, although without any apparent clinical effects, compared with none in the placebo group. The most common adverse events were bone pain (41% vs. 48%, respectively); fatigue (39% vs. 34%); constipation (32% vs. 26%); and nausea (23% vs. 24%). Most of the adverse events were mild—i.e., grade 1 or 2.
The study was published simultaneously in Lancet Oncology (2015;16:1463-1472).
Pain Flare Common
Speaking at an ASTRO news conference on “Improving Value and Elevating the Patient Care Experience” that featured the study, another of the coauthors, Alysa Fairchild, MD, a radiation oncologist at Cross Cancer Institute and the University of Alberta, noted that up to 45 percent of patients receiving palliative radiotherapy for bone metastases will experience an acute pain flare, with the pain usually resolving within 10 days.
“Pain flare is temporary, but it can be quite severe. It decreases quality of life, can increase the need for pain medication, and potentially contributes to aversion to future radiation.”
The flare may be caused by increasing inflammation, she said. Dexamethasone, an oral anti-inflammatory agent, has analgesic properties, and furthermore, is inexpensive.
“The potential side effects of radiation treatment for bone metastases can be well managed in the majority of people, and pain flare should not be viewed as a barrier to receiving this highly effective therapy for symptom control,” Fairchild said.
“A short course of dexamethasone to reduce the risk of experiencing an acute pain flare should be recommended as standard of care for all patients receiving radiation for bone metastases.”
‘Stitch in Time’
The moderator of the news conference, Brian Kavanagh, MD, Interim Chair of the Department of Radiation Oncology at the University of Colorado School of Medicine, said the study is an illustration of “a stitch in time saves nine—It's better to prevent the problem and avoid the issue rather than try to play catch up.”
He said patients might typically be advised to increase the doses of pain medication for pain flare, which would carry with it increased opioid side effects, which can be troublesome to manage—“These researchers were able to avoid extra pain medication down the road if they used only a few doses of a very well tolerated medication.
“This study reminds us that sometimes we don't need to use extremely high-tech modalities—sometimes the appropriate use of a good medication that's even been around for a while can augment the efficacy of treatment and avoid some temporary side effects.”