Trial Methods No. of patients Technique Outcomes 89Sr compared to placebo Lewington et al. (Phase III cross over) [4]. 89Sr vs.placebo 32 150 MBq week 1and 150 MBq in week 6 if needed Pain reduction for 89Sr arm (p<0.01) Buchali et al. (Phase I/II) [15]. 89Srvs. placebo 49 75 MBqqmonths x 3 months NSD# after 1-3 years improved 2years OS (46% vs. 4%) in 89Sr arm Adjuvant 89Sr compared to placebo Porter et al. (Phase III) [16] 89Sras adjunctive therapy to local XRT compared with placebo 126 Involved field XRT and 10.8 mCi (400MBq) injection Fewer new pain sites in 89Sr group NSD pain relief or median survival. 89Sr arm better in need of analgesics, time to further XRT and further quality of life. Smeland et al. (phase III) [17]. EBRT + 89Srvs. EBRT + placebo 95 (64 prostate) 150 MBq No adjuvant benefit to 89Sr with EBRT No survival or QOL, PSA difference 89Sr compared to EBRT Quilty et al. (stratum I)Phase III [19]. 89Sr with EBRT (involved field) 148 200MBq NSD in pain relief or survival, decreased new sites and further XRT. Quilty et al. (stratum II) Phase III [19] 89Sr with EBRT (hemibody RT) 157 200MBqvs. 6 Gy upper , 8 Gy lower NSD in pain relief or median survival 89Sr reduced new pain sites Oosterhof et al., Phase III [20]. EBRT vs.89Sr 203 150MBq (4mCi) Better OS with XRT (11months vs. 7.2 months) No difference in PSA response 89Sr vs.153Sm Baczyk et al. [21] 89Sr vs. 153Sm 50 89Sr(150 MBq)vs. 153Sm(37 MBq per kg) NSD pain relief. Better response for blastic metastasis than mixed. 89Sr vs. chemotherapy alone Tu et al.[22] Induction chemo followed by randomisation todoxorubicin with or without 6 weekly 89Sr 89 72 2·035 MBq per kg Significant survival advantage for addition of 89Sr (27.7 vs. 16.8 mo) Nilsson et al. [23] 89Sr (18) vs. 5-FU, epirubicin, mitomycin-C 35 150 MBq (4mCi) At 3 weeks, pain reduced in both groups (p = 0.01 and 0.001 respectively) No differences in Karnofsky performance status or analgesic use More side effects in the chemo arm. 153Sm vs. placebo Serafini et al.[24] 153Sm vs. placebo 118 0.5-1 mCi/kg (18.5-37 MBq/kg) 62–72% of patients had \pain relief with 1.0 mCi/ kg during first 4 weeks and 31% had complete/ marked relief by week 4 Sartor et al. [25] 153Sm (101) vs. placebo (51) 152 1 mCi/kg (37 MBq/kg) Significant improvement in bone pain and analgesic use with Sm-153 (p<0.05) 153Sm 0.5 vs. 1.0 Resche et al. [26] 153Sm at 0.5 mCi/ kg (55) vs. 1.0 mCi/ kg (59) 114 (67 prostate) 153Sm at 0.5 mCi/ kg (55) vs. 1.0 mCi/ kg (59) 55% vs. 70% pain relief between 0.5 mc9 and 1.0 mci at week 4 (p = 0.0476) OS not differentbetween groups 186Re vs. placebo Han et al. Phase III [27] (PLACORHEN study) 186Re vs. Placebo 79 1,295 to 2,960 MBq (35–80 mCi) Mean percentage of pain response days 27% (186Re) vs. 13% (placebo), p<0.05 Median survival 37.2 weeks(placebo) vs. 30.4 weeks (186Re), p > 0.05 Radiotherapy for pain required in 44% (186Re) vs. 67% (placebo) Maxon et al. Phase III crossover [28] 186Re (6) vs. Placebo 20 (9 prostate) 30-35 mCi (1110-1295 MBq) Significantly greater relief in pain with 186Re (p<0.05). Higher leukopenia in Re arm 223Ra vs. placebo Parker et al. [29] Phase III (ALSYMPCA trial) 223Ra (541) vs. placebo (268) 809 (50 kBq/kg IV) q4weeks OS: 14 months (223Ra) vs.11.2 months (placebo), HR 0.695, p = 0.001 HR time to total ALP progression: 0.163 (p<0.00001), HR for time to PSA progression: 0.671(p = 0.0002),

Table 2: Table demonstrating the various randomised trials in bone seeking radionuclide therapy. #No significant difference.