Hoskin, P., Sundar, S., Reczko, K., Forsyth, S., Mithal, N., Sizer, B., . . . Hackshaw, A. (2015). A multicenter randomized trial of ibandronate compared with single-dose radiotherapy for localized metastatic bone pain in prostate cancer. Journal of the National Cancer Institute, 107, djv197. 

To compare a single, intravenous infusion of ibandronate with single-dose radiotherapy for metastatic bone pain

Patients referred for pain management were randomized to receive 6 mg ibandronate or a single dose of 8 Gy radiotherapy. Patients whose pain failed to respond to the treatment at four weeks were allowed to cross over to the opposite treatment within four to eight weeks. Assessments were done at baseline and at four, eight, 12, 26, and 52 weeks.

• N = 470
• MEDIAN AGE = 72.5 years (range = 47–97 years)
• MALES: 100%
• KEY DISEASE CHARACTERISTICS: All had prostate cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Patients who had previous treatment with radiotherapy or bisphosphonates within the last six months were excluded. Overall, 90% were receiving hormone therapy. The baseline median pain score was 7.

• SITE: Multi-site  
• SETTING TYPE: Outpatient  
• LOCATION: United Kingdom

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care 

Randomized noninferiority trial

• World Health Organization (WHO) criteria for analgesia
• Morphine equivalents for analgesia use
• Brief Pain Inventory (BPI)
• Effective Analgesic Score (EAS)
• Functional Assessment of Chronic Illness Therapy (FACIT) for quality of life
• Complete response was defined as a pain score of 0 with stable or reduced analgesic use.
• Partial response was defined as a two-point reduction in pain scores or a 25% reduction in analgesia with a stable pain score.

Overall, 31% of participants who began with ibandronate were crossed over, and 24% who began with radiotherapy were crossed over. There was no difference in WHO worst pain response between the groups at any study assessment period. There were no differences between the groups in worst pain response. At four weeks, those receiving radiotherapy had better responses (p = 0.04), but there was no difference at 12 weeks. There were no differences in quality of life between groups. Twice as many patients in the radiotherapy group had diarrhea (p = 0.014), and more had nausea (p = 0.058).

Single-dose radiotherapy and a single infusion of ibandronate had similar results on pain caused by bone metastases in men with prostate cancer. Radiotherapy was associated with more short-term adverse effects.

• Risk of bias (no blinding)
• Unintended interventions or applicable interventions not described that would influence results
• Other limitations/explanation: No information was provided regarding analgesics used, and data regarding any changes in analgesia were not provided.

This study showed similar results for pain reduction with single-dose radiotherapy and a single infusion of ibandronate. Ibandronate is a newer bone modifying agent, so it is not clear if all bone modifying agents would provide equivalent results in comparison to radiotherapy. Bone modifying agents may have fewer side effects, which can be of importance depending upon the site of radiotherapy.