Flares of bone pain decreased significantly when the oral corticosteroid dexamethasone was added to radiation therapy in patients with metastatic cancer, according to a randomized, placebo-controlled trial.
Flares of bone pain decreased significantly when the oral corticosteroid dexamethasone was added to radiation therapy in patients with metastatic cancer, according to results of a randomized, placebo-controlled trial presented at the 2015 ASTRO Annual Meeting.
About a fourth of patients treated with dexamethasone had bone pain flares compared with 35% of those randomized to placebo. A sensitivity analysis that accounted for patients with missing data showed a similar difference in flare rate between the dexamethasone and placebo groups. Patients in the dexamethasone arm also had significant improvement in nausea, functional interference, and appetite as compared with the placebo group.
“We believe that pain flare should no longer be seen as a barrier to receiving a highly effective therapy for bone pain,” said Alysa M. Fairchild, MD, a radiation oncologist at Cross Cancer Institute in Edmonton, Alberta. “This inexpensive pill can help avoid debilitating pain due to treatment. It was well tolerated and improved patients’ quality of life.”
Bone metastases can cause severe, debilitating pain, which a single session of palliative radiation therapy can relieve in a majority of patients. However, in as many as 45% of cases, radiotherapy causes a temporary paradoxical exacerbation or flare of bone pain. The flare adversely affects quality of life, increases use of analgesic medication, and can lead some patients to develop an aversion to subsequent radiation therapy sessions, said Fairchild.
Data from preliminary studies have suggested that short-term administration of dexamethasone can reduce the frequency of flares in bone pain. The magnitude of benefit has ranged from 15% to 35% reductions in the frequency of bone pain flare. The observations had not been confirmed in a randomized trial, providing a rationale for the trial conducted by the National Cancer Institute of Canada.
The trial involved 298 patients scheduled to receive a single 8-Gy dose of radiation therapy for one or two bone metastases. Patients were randomized to placebo or to dexamethasone 8 mg/day for 5 days, beginning the day of the radiation treatment. The primary endpoint of the trial was incidence of bone pain flares. Secondary endpoints included toxicity and quality-of-life.
Patients reported their worst pain before radiation therapy and for 10 days afterward. Patients completed two quality-of-life questionnaires and the Dexamethasone Symptom Questionnaire at baseline and at 10 and 42 days after radiation therapy.
Investigators used two definitions of pain flare to evaluate the results: a minimum 2-point increase in patient-reported worst pain on a scale of 0 to 10 with no decrease in analgesic use; or at least a 25% increase in analgesic intake with no decrease in the worst-pain score.
By intention-to-treat (ITT) analysis, 26.4% of patients in the dexamethasone group had flares of bone pain versus 35.3% of patients in the placebo group (P= .05). Investigators performed a sensitivity analysis of the data, counting patients with incomplete data as not evaluable. This analysis showed a bone-pain flare incidence of 17.6% in the dexamethasone group and 29.3% in the placebo group (P= .01).
The overall benefit seen across the full study was largely driven by a reduction in pain flares during the first 5 days, said co-investigator Edward Chow, MD, a professor of radiation oncology at Sunnybrook Odette Cancer Center in Toronto. In fact, during the first 5 days, the ITT analysis showed a flare incidence of just 19.6% in the dexamethasone group versus 30.7% with placebo (P= .03). From day 6 to 10, flare incidence was virtually identical in the two groups: 18.9% with dexamethasone and 18.7% with placebo.
The sensitivity analysis confirmed the early benefit of dexamethasone therapy. Flare incidence was 8.8% and 20.7% during days 0 to 5 in the dexamethasone and placebo groups, respectively. During days 6 to 10, flare incidence was 8.8% with placebo and 8.7% with placebo.
The most notable toxicity consisted of three cases of grade 3/4 hyperglycemia, none of which led to known clinical consequences, said Fairchild.
Assessment of secondary endpoints showed that patients assigned to dexamethasone had significant improvement from baseline to 10 days after radiotherapy in nausea, interference with normal activities, and appetite as compared with the placebo group.