Dexamethasone reduces radiation therapy–induced pain flare

SAN ANTONIO – Dexamethasone given before radiotherapy for bone metastases reduced the risk for subsequent pain flare by 8.9% when compared with placebo in a double blind, randomized phase III trial.

Of the 148 patients treated with the steroid, 26.4% experienced a pain flare up to 10 days after an 8-Gy dose of radiation was given versus 35.3% of the 150 patients who had received placebo (P = .05) in an intent-to-treat analysis. The first 8-mg oral dose of dexamethasone was given at least 1 hour before the single shot of palliative radiotherapy and continued for 4 days.

Sara Freeman/Frontline Medical News

“Bone metastases are very prevalent in advanced cancer,” Dr. Edward Chow of Sunnybrook Health Sciences Center in Toronto said at the annual meeting of the American Society for Radiation Oncology.

“Palliative radiotherapy is effective in the treatment of painful bone metastases but acute pain flare can occur,” he said. Previous research from three Canadian centers had shown that up to 40% of patients can experience an acute and temporary worsening of pain during, or for up to 10 days after, palliative radiotherapy.

As the impact of these pain flares can be severe, often interfering with patients’ daily activities and ability to function normally, as well as causing additional anxiety about the success of treatment, Dr. Chow and associates aimed to see if the anti-inflammatory action of dexamethasone might stop them from happening. Two prior pilot studies had suggested that it might, but a randomized controlled trial was needed.

The phase III trial (results also published in the Lancet Oncology to coincide with presentation at the meeting) was conducted between May 2011 and Dec 2014 at 23 Canadian centers. Just under 300 patients with a median age of 69 years who were due to undergo palliative radiation therapy were enrolled into the trial, of whom 28% had lung cancer, 25% had prostate cancer, and 22% had breast cancer. The remainder (25%) had other cancers, but these excluded hematologic malignancies since corticosteroids can be used as anticancer therapy in these patients.

Patients recorded their level of pain in a diary using a scale of 0, meaning no pain, to 10, meaning the worst possible pain, before radiation and then for 10 days after treatment. The primary endpoint was the per-patient incidence of pain flare, defined as either a two-point increase in the pain score without a reduction in analgesic use or a 25% or greater reduction in analgesic use without a reduction in the pain score.

Dr. Chow reported that pain flares occurring in the first 5 days of follow-up were significantly less common in the dexamethasone- than placebo-treated patients, at 19.5% and 30.7%, with an absolute difference of 11.1% (P = .03), but that there was no significant difference from days 6-10. Similar results were seen in a sensitivity analysis.

A secondary endpoint was the proportion of patients achieving an overall response to radiation therapy, which showed no difference between the groups. “Whether a patient developed a pain flare or not was not predictive of radiation response in either arm,” Dr. Chow reported.

Adverse effects were mostly grade 1 or 2 and there was no statistical difference between the two groups, he added. Three patients treated with dexamethasone experienced hyperglycemic events identified by biochemistry rather than clinical presentation, none of which required hospitalization. There were a similar number of deaths, 11 in the dexamethasone arm and 15 in the placebo arm, none of which were related to treatment.

Several validated measures were used to assess patient quality of life, including the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life QLQ-C15-PAL questionnaire, the EORTC QLQ-BM22 bone metastases module, and the Dexamethasone Symptom Questionnaire (DSQ). Results showed patients treated with dexamethasone had significant improvements in nausea, function interference, and appetite by day 10 and improved physical domains and sleep by day 42. There was also an indication of better DSQ depression scores at day 42 with the steroid treatment.

“Given how easy and inexpensive this treatment is we believe that it should become standard of care for patients getting palliative radiotherapy for painful bone metastases as it seems to improve both pain associated with radiation treatment and also quality of life,” said coinvestigator Dr. Alysa Fairchild of the Cross Cancer Institute in Edmonton in an interview.

“We believe that our study results are robust, and this is a fairly large sample size across many Canadian centers so we believe these results are practice changing,” she added. “Ideally it would be nice to be able to predict which of the patients treated with [radiation therapy] are going to experience a pain flare, but at present we are not able to do that, so we do believe that dexamethasone should be given to everybody undergoing this type of [radiation] treatment.”

In an editorial accompanying the published findings, however, Dr. Barry Laird and Dr. Marnie Fallon of the University of Edinburgh in Scotland, comment: “Although the findings are encouraging, caution is advised before dexamethasone is used routinely to prevent pain flares after radiotherapy.”

While they commend the research team for performing the trial in this advanced cancer patient population, they note that the small reduction in pain flares seen may not be sufficient to warrant routine treatment with dexamethasone. They point out that the number needed to treat (NNT) was high, at 9-11, and that other analgesics, such as strong opioids had lower NNT (3-4) and so could perhaps be used instead. Steroids can also have adverse effects on muscle mass and glycemic control, they observed.

Dr. Chow, Dr. Fairchild, and a third investigator reported having no disclosures. The study was funded by a grant from the Canadian Cancer Society Research Institute.

SAN ANTONIO – Dexamethasone given before radiotherapy for bone metastases reduced the risk for subsequent pain flare by 8.9% when compared with placebo in a double blind, randomized phase III trial.

Of the 148 patients treated with the steroid, 26.4% experienced a pain flare up to 10 days after an 8-Gy dose of radiation was given versus 35.3% of the 150 patients who had received placebo (P = .05) in an intent-to-treat analysis. The first 8-mg oral dose of dexamethasone was given at least 1 hour before the single shot of palliative radiotherapy and continued for 4 days.

Sara Freeman/Frontline Medical News

“Bone metastases are very prevalent in advanced cancer,” Dr. Edward Chow of Sunnybrook Health Sciences Center in Toronto said at the annual meeting of the American Society for Radiation Oncology.

“Palliative radiotherapy is effective in the treatment of painful bone metastases but acute pain flare can occur,” he said. Previous research from three Canadian centers had shown that up to 40% of patients can experience an acute and temporary worsening of pain during, or for up to 10 days after, palliative radiotherapy.

As the impact of these pain flares can be severe, often interfering with patients’ daily activities and ability to function normally, as well as causing additional anxiety about the success of treatment, Dr. Chow and associates aimed to see if the anti-inflammatory action of dexamethasone might stop them from happening. Two prior pilot studies had suggested that it might, but a randomized controlled trial was needed.

The phase III trial (results also published in the Lancet Oncology to coincide with presentation at the meeting) was conducted between May 2011 and Dec 2014 at 23 Canadian centers. Just under 300 patients with a median age of 69 years who were due to undergo palliative radiation therapy were enrolled into the trial, of whom 28% had lung cancer, 25% had prostate cancer, and 22% had breast cancer. The remainder (25%) had other cancers, but these excluded hematologic malignancies since corticosteroids can be used as anticancer therapy in these patients.

Patients recorded their level of pain in a diary using a scale of 0, meaning no pain, to 10, meaning the worst possible pain, before radiation and then for 10 days after treatment. The primary endpoint was the per-patient incidence of pain flare, defined as either a two-point increase in the pain score without a reduction in analgesic use or a 25% or greater reduction in analgesic use without a reduction in the pain score.

Dr. Chow reported that pain flares occurring in the first 5 days of follow-up were significantly less common in the dexamethasone- than placebo-treated patients, at 19.5% and 30.7%, with an absolute difference of 11.1% (P = .03), but that there was no significant difference from days 6-10. Similar results were seen in a sensitivity analysis.

A secondary endpoint was the proportion of patients achieving an overall response to radiation therapy, which showed no difference between the groups. “Whether a patient developed a pain flare or not was not predictive of radiation response in either arm,” Dr. Chow reported.

Adverse effects were mostly grade 1 or 2 and there was no statistical difference between the two groups, he added. Three patients treated with dexamethasone experienced hyperglycemic events identified by biochemistry rather than clinical presentation, none of which required hospitalization. There were a similar number of deaths, 11 in the dexamethasone arm and 15 in the placebo arm, none of which were related to treatment.

Several validated measures were used to assess patient quality of life, including the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life QLQ-C15-PAL questionnaire, the EORTC QLQ-BM22 bone metastases module, and the Dexamethasone Symptom Questionnaire (DSQ). Results showed patients treated with dexamethasone had significant improvements in nausea, function interference, and appetite by day 10 and improved physical domains and sleep by day 42. There was also an indication of better DSQ depression scores at day 42 with the steroid treatment.

“Given how easy and inexpensive this treatment is we believe that it should become standard of care for patients getting palliative radiotherapy for painful bone metastases as it seems to improve both pain associated with radiation treatment and also quality of life,” said coinvestigator Dr. Alysa Fairchild of the Cross Cancer Institute in Edmonton in an interview.

“We believe that our study results are robust, and this is a fairly large sample size across many Canadian centers so we believe these results are practice changing,” she added. “Ideally it would be nice to be able to predict which of the patients treated with [radiation therapy] are going to experience a pain flare, but at present we are not able to do that, so we do believe that dexamethasone should be given to everybody undergoing this type of [radiation] treatment.”

In an editorial accompanying the published findings, however, Dr. Barry Laird and Dr. Marnie Fallon of the University of Edinburgh in Scotland, comment: “Although the findings are encouraging, caution is advised before dexamethasone is used routinely to prevent pain flares after radiotherapy.”

While they commend the research team for performing the trial in this advanced cancer patient population, they note that the small reduction in pain flares seen may not be sufficient to warrant routine treatment with dexamethasone. They point out that the number needed to treat (NNT) was high, at 9-11, and that other analgesics, such as strong opioids had lower NNT (3-4) and so could perhaps be used instead. Steroids can also have adverse effects on muscle mass and glycemic control, they observed.

Dr. Chow, Dr. Fairchild, and a third investigator reported having no disclosures. The study was funded by a grant from the Canadian Cancer Society Research Institute.

SAN ANTONIO – Dexamethasone given before radiotherapy for bone metastases reduced the risk for subsequent pain flare by 8.9% when compared with placebo in a double blind, randomized phase III trial.

Of the 148 patients treated with the steroid, 26.4% experienced a pain flare up to 10 days after an 8-Gy dose of radiation was given versus 35.3% of the 150 patients who had received placebo (P = .05) in an intent-to-treat analysis. The first 8-mg oral dose of dexamethasone was given at least 1 hour before the single shot of palliative radiotherapy and continued for 4 days.

Sara Freeman/Frontline Medical News

“Bone metastases are very prevalent in advanced cancer,” Dr. Edward Chow of Sunnybrook Health Sciences Center in Toronto said at the annual meeting of the American Society for Radiation Oncology.

“Palliative radiotherapy is effective in the treatment of painful bone metastases but acute pain flare can occur,” he said. Previous research from three Canadian centers had shown that up to 40% of patients can experience an acute and temporary worsening of pain during, or for up to 10 days after, palliative radiotherapy.

As the impact of these pain flares can be severe, often interfering with patients’ daily activities and ability to function normally, as well as causing additional anxiety about the success of treatment, Dr. Chow and associates aimed to see if the anti-inflammatory action of dexamethasone might stop them from happening. Two prior pilot studies had suggested that it might, but a randomized controlled trial was needed.

The phase III trial (results also published in the Lancet Oncology to coincide with presentation at the meeting) was conducted between May 2011 and Dec 2014 at 23 Canadian centers. Just under 300 patients with a median age of 69 years who were due to undergo palliative radiation therapy were enrolled into the trial, of whom 28% had lung cancer, 25% had prostate cancer, and 22% had breast cancer. The remainder (25%) had other cancers, but these excluded hematologic malignancies since corticosteroids can be used as anticancer therapy in these patients.

Patients recorded their level of pain in a diary using a scale of 0, meaning no pain, to 10, meaning the worst possible pain, before radiation and then for 10 days after treatment. The primary endpoint was the per-patient incidence of pain flare, defined as either a two-point increase in the pain score without a reduction in analgesic use or a 25% or greater reduction in analgesic use without a reduction in the pain score.

Dr. Chow reported that pain flares occurring in the first 5 days of follow-up were significantly less common in the dexamethasone- than placebo-treated patients, at 19.5% and 30.7%, with an absolute difference of 11.1% (P = .03), but that there was no significant difference from days 6-10. Similar results were seen in a sensitivity analysis.

A secondary endpoint was the proportion of patients achieving an overall response to radiation therapy, which showed no difference between the groups. “Whether a patient developed a pain flare or not was not predictive of radiation response in either arm,” Dr. Chow reported.

Adverse effects were mostly grade 1 or 2 and there was no statistical difference between the two groups, he added. Three patients treated with dexamethasone experienced hyperglycemic events identified by biochemistry rather than clinical presentation, none of which required hospitalization. There were a similar number of deaths, 11 in the dexamethasone arm and 15 in the placebo arm, none of which were related to treatment.

Several validated measures were used to assess patient quality of life, including the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life QLQ-C15-PAL questionnaire, the EORTC QLQ-BM22 bone metastases module, and the Dexamethasone Symptom Questionnaire (DSQ). Results showed patients treated with dexamethasone had significant improvements in nausea, function interference, and appetite by day 10 and improved physical domains and sleep by day 42. There was also an indication of better DSQ depression scores at day 42 with the steroid treatment.

“Given how easy and inexpensive this treatment is we believe that it should become standard of care for patients getting palliative radiotherapy for painful bone metastases as it seems to improve both pain associated with radiation treatment and also quality of life,” said coinvestigator Dr. Alysa Fairchild of the Cross Cancer Institute in Edmonton in an interview.

“We believe that our study results are robust, and this is a fairly large sample size across many Canadian centers so we believe these results are practice changing,” she added. “Ideally it would be nice to be able to predict which of the patients treated with [radiation therapy] are going to experience a pain flare, but at present we are not able to do that, so we do believe that dexamethasone should be given to everybody undergoing this type of [radiation] treatment.”

In an editorial accompanying the published findings, however, Dr. Barry Laird and Dr. Marnie Fallon of the University of Edinburgh in Scotland, comment: “Although the findings are encouraging, caution is advised before dexamethasone is used routinely to prevent pain flares after radiotherapy.”

While they commend the research team for performing the trial in this advanced cancer patient population, they note that the small reduction in pain flares seen may not be sufficient to warrant routine treatment with dexamethasone. They point out that the number needed to treat (NNT) was high, at 9-11, and that other analgesics, such as strong opioids had lower NNT (3-4) and so could perhaps be used instead. Steroids can also have adverse effects on muscle mass and glycemic control, they observed.

Dr. Chow, Dr. Fairchild, and a third investigator reported having no disclosures. The study was funded by a grant from the Canadian Cancer Society Research Institute.