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 II 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 II 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 II trials, one randomized crossover trial and 13 phase II or phase I trials of
rhenium, one phase I trial of
tin-117 m and one phase II 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: