Radiopharmaceuticals for the palliation of painful bone metastases - a systematic review

Background and Purpose: The purpose was to develop a systematic review that would address the following question: what is the role of radiopharmaceuticals in the palliation of metastatic bone pain in adults with uncomplicated, multifocal painful bone metastases whose pain is not controlled with conventional analgesic regimens? The outcomes of interest are pain response, analgesic consumption, overall survival, adverse effects and quality of life. Materials and methods: A systematic review of the English published literature was undertaken to provide evidence relevant to the above outcomes. Results: Six randomized phase III trials, two randomized phase 11 trials and one randomized crossover trial of strontium-89 were reviewed. A randomized phase III trial comparing strontium-89 plus cisplatin with strontium-89 plus placebo reported a significantly higher proportion of patients experiencing pain relief for a significantly longer duration with strontium-89 plus cisplatin. A randomized phase III trial comparing adjuvant strontium-89 with placebo following radiotherapy reported a higher proportion of pain-free patients with strontium-89. Patients who received strontium-89 also experienced fewer new sites of bone pain. A second, but underpowered study failed to confirm these results. In one randomized trial of strontium-89 versus radiotherapy (hemibody or local), patients treated with strontium-89 developed fewer new sites of pain. In a second trial comparing strontium-89 versus local radiotherapy, median overall survival was improved with radiotherapy, while pain response and time-to-progression were similar in the two groups. One randomized phase III trial reported no difference in pain relief between strontium-89 and placebo. Three randomized phase III trials and two randomized phase 11 trials investigating samarium-153 were reviewed. In a randomized phase III trial of three different doses of samarium-153, the pain responses were similar for all three doses. In a randomized phase III trial of two different doses of samarium-153 versus placebo, the complete pain response rate was significantly higher with the higher dose of samarium-153 compared with placebo. In a randomized phase III trial comparing samarium-153 with placebo, significant differences favouring samarium-153 were reported for pain and opiate use. In addition, one randomized phase III trial, two randomized phase 11 trials, one randomized crossover trial and 13 phase 11 or phase I trials of rhenium, one phase I trial of tin-117 m and one phase 11 trial of phosphorus-32 were reviewed. The majority of patients treated in trials of radiopharmaceuticals where histology was specified had metastatic breast cancer (approximately 5-10% of patients reported), metastatic hormone-refractory prostate cancer (80-90% of patients reported) or metastatic lung cancer (5-10% of patients reported). Information on histologic subtype was not available for a significant proportion of patients treated on trials (30-40% of patients reported). Conclusions: Use of single-agent radiopharmaceuticals (strontium-89 and samarium-153) should be considered as a possible option for the palliation of multiple sites of bone pain from metastatic cancer where pain control with conventional analgesic regimens is unsatisfactory and where activity on a bone scan of the painful lesions is demonstrated. Ongoing clinical research should seek to establish the benefit of newer radiopharmaceuticals and radiopharmaceuticals in combination with other systemic therapies. (C) 2005 Elsevier Ireland Ltd. All rights reserved.