Dexamethasone Prophylaxis Potential for Radiation-Induced Pain Flare

Researchers suggest pretreatment with dexamethasone to prevent pain flares after radiotherapy for bone metastases

medwireNews: Patients who experience pain flare as a result of palliative radiotherapy for symptomatic bone metastases could benefit from prophylactic treatment with dexamethasone, suggest findings published in The Lancet Oncology.

Researcher Edward Chow, from Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada, and fellow investigators explain that although radiotherapy is an effective treatment option for painful bone metastases, 30–40% of patients experience acute pain flare.

In this double-blind phase III trial, they compared the efficacy of dexamethasone 8 mg with placebo for the attenuation of pain flare. Both dexamethasone and placebo were taken at least an hour prior to receiving a single fraction of palliative radiotherapy and subsequently every day for 4 days.

Twenty-six percent of 148 patients randomly assigned to receive dexamethasone experienced pain flare from the time of radiotherapy until 10 days after treatment (0–10 days). Among the 150 participants given placebo, the incidence of pain flare was 35%, with an absolute between-group difference of 8.9% (p=0.05).

Between days 0 and 5, a significantly smaller proportion of dexamethasone-treated compared with placebo-treated patients experienced pain flare, at 20% versus 31%, with an absolute difference between groups of 11.1%. However, the treatment arms were comparable with respect to pain flare incidence between days 6 and 10.

A sensitivity analysis that assumed that patients with missing data in either group did not have pain flare on days 0–10 found a significantly lower incidence of pain flare in the dexamethasone than in the placebo group, at 18% and 29%, respectively. The absolute difference between treatment arms was 11.8%.

The team reports that the number needed to treat increased from a hypothesised six to an observed 11 in the intention-to-treat analysis and nine in the sensitivity analysis.

Dexamethasone-treated patients reported significant reductions in nausea and functional interference, and improvements in appetite at day 10 compared with baseline. And significantly more patients in the dexamethasone than the placebo group reported these quality of life improvements, which were assessed using the bone metastases module of the EORTC Quality of Life QLQ-C15-PAL questionnaire.

Bone pain of grade 3 or higher occurred in 7% of patients in the dexamethasone arm and in 14% of those in the placebo arm. And 2% of dexamethasone-treated patients but none of their placebo-treated counterparts experienced grade 3 or worse hyperglycaemia.

The researchers suggest that “prophylactic use of dexamethasone should be adopted as standard of care for patients receiving palliative radiotherapy for treatment of painful bone metastases.”

Commentators Barry Laird and Marie Fallon, from the University of Edinburgh in the UK, commend the authors on their robust clinical trial in this setting.

But they point out that the number needed to treat is high, and other analgesics such as strong opioids with a lower number needed to treat (3–4) could be used instead.

Moreover, although the reported beneficial effects on quality of life are not in question, steroids can adversely affect muscle mass and glycaemic control, write the commentators.

“Therefore, although the findings are encouraging, caution is advised before dexamethasone is used routinely to prevent pain flares after radiotherapy.

“In relation to the mechanism of analgesic action, being mindful of the general effects of steroids is important, such as improved sense of wellbeing, which could arguably attenuate the subjective pain experience”, they conclude.


Chow E, Meyer RM, Ding K, et al. Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial. Lancet Oncol; Advance online publication 18 October 2015. doi:

Laird BJ, Fallon M. Attenuating pain flare: a new role for an old therapy? Lancet Oncol; Advance online publication 18 October 2015. doi:

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