Pirayesh, E., Amoui, M., Mirzaee, H.R., Tabei, F., Rakhsha, A., Kalantari, B.A., . . . Asli, I.N. (2013). Phase 2 study of a high dose of 186Re-HEDP for bone pain palliation in patients with widespread skeletal metastases. Journal of Nuclear Medicine Technology, 41, 192–196. 

To investigate the efficacy and side effects of the 186Re-hydroxyethylidene diphosphonate (HEDP) radiopharmaceutical for the treatment of pain from skeletal metastases in patients with different types of cancer

Whole-body scans and assessments were done, and patients' symptoms were evaluated to determine whether they had simple metastatic bone pain. Patients were admitted to the day-care unit and received 1,480–3,330 MBq of 186Re-HEDP in saline intravenously over 10 minutes. All patients received oral or intravenous hydration before and after infusion. Whole-body scanning was done 4–24 hours later, and external dosimetry was done at zero, one, two, four to six, and 24 hours after injection.

• N = 20  
• MEAN AGE = 55 years (range = 30–75 years)
• MALES: 40%, FEMALES: 60%
• KEY DISEASE CHARACTERISTICS: Breast, prostate, colon, renal cell, neuroendocrine, and synovial sarcoma
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were excluded if they had impending or actual fracture, impending or existing spinal cord compression, or had received hemi- or whole-body radiation in the previous three months.

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: Iran

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

Phase-II observational study

• Visual Analogue Scale (VAS, 0–10)
• Dosage and type of pain medication graded from 0 (non opioids) to 3 (strong opioids) 
• Bone-scan index calculated as sum of scores of anatomic regions

The mean dose administered was 2,882 ± 675 MBq. The distribution of the tracer was seen within 4–24 hours and was correlated with the pretreatment whole-body scan. Pain relief began at around seven days after treatment. Response was observed for at least one week in 78.9% of patients and for two weeks in 63.2%. The mean duration of pain relief was 5.26 weeks (range = 1–8 weeks). There was a significant reduction of greater than three points in the first week (p = .0001) and, on average, the pain scale rating remained about 3 points below baseline at week 8 (p = .007). A transient decrease in platelets, white blood cells (WBC), and hemoglobin counts was seen. Four patients showed grade-3 platelet toxicity, 56% had at least grade-1 WBC toxicity, and 14.3% had at least a grade-2 decline in hemoglobin. A flare reaction, with a short-term worsening of bone pain, was seen in 53.5% of those who responded to the treatment and appeared to be dose-related.

186Re-HEDP may be an effective radiopharmaceutical for the palliation of metastatic bone pain.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Other limitations/explanation: The toxicity grading used was not described. Pain medications used are not described, and prior approaches in bone pain management are not described.

Pain from bone metastases is one of the most challenging areas in patients with advanced cancer. This radiopharmaceutical may provide another alternative option for pain management; however, further research is needed to determine its efficacy and toxicities and to determine the actual duration of effects. Patients receiving this agent need to be observed for bone marrow toxicities.