Table 3.
Summary of studies describing therapeutic efficacy of samarium-153 in metastatic prostate cancer.
| Study | Treatment (# patients) | Primary endpoint | Results | Other outcomes | Adverse effects | Comments |
|---|---|---|---|---|---|---|
| Collins et al. [75] Phase I/II | Escalated doses of Sm-153 from 1.0 mCi/kg to 2.5 mCi/kg (52) | Pain response | Overall pain response 76% | Median OS better with higher dose (9 mos vs. 6 mos, p = 0.03) | Increased hematological toxicity with higher dose | Higher dose experienced greater reduction in opioid use |
| Valicenti et al. [73] Phase I | Escalated doses of Sm-153 from 0.2 mCi/kg to 2.0 mCi/kg (29) | Grade ≥ 3 toxicity | – | – | Grade-3 anemia and/or thrombocytopenia in 3.57% of patients | Significant dose-response in nadir platelet count at 4 wks |
| Sandeman et al. [74] Phase I | Escalated dose of Sm-153 from 1.5 Gy to 4.5 Gy (9) | Pain relief | 88.8% patients had at least some relief of pain | – | Thrombocytopenia in 44.4% patients | Pain relief delayed for 2 wks but maximal 4 wks |
| Dolezal et al. [76] Phase I | Sm-153 at dose of 40 MBq/kg (32) | Pain relief | At 3 mos, significant pain relief in 38% patients and some pain relief in 72% | – | 2 patients had grade-3 hematological toxicity, no grade-4 toxicities | Reduction in analgesic requirement |
| Morris et al. [79] Phase I | Escalated doses of Sm-153 from 0.5 to 1.0 mCi/kg and docetaxel from 65 to 75 mg/m2 (28) | Safety | 15 patients had >50% decline in PSA | – | No dose-limiting toxicity | Significant changes in urine and serum N-telopeptides, and osteocalcin |
| Fizazi et al. [80] Phase II | Sm-153 with docetaxel (43) | PSA-PFS | Median PSA-PFS was 6.4 mos | Median OS was 29 mos | 2 patients (5%) had grade-3 thrombocytopenia | PSA response in 77%, pain response rate 69% |
| Serafini et al. [77] Phase III | Sm-153 at 0.5 mCi/kg (40) or 1.0 mCi/kg (39) vs. placebo (39) | Pain relief | 62–72% of patients had pain relief with 1.0 mCi/kg during first 4 wks and 31% had complete/marked relief by wk 4 | – | With 1.0 mCi/kg: grade-3/4 anemia in 6%, thrombocytopenia in 3% and leukopenia in 14% (compared to 35%, 0% and 0% respectively with placebo) | Significant correlation between reduction of analgesic use and pain scores (with 1.0 mCi/kg) |
| Sartor et al. [78] Phase III | Sm-153 (101) vs. placebo (51) | Pain relief | Significant improvement in bone pain and analgesic use with Sm-153 (p < 0.05) | – | With Sm-153: grade-3 thrombocytopenia in 3% and leukopenia in 5% (vs. none in placebo) | – |
| Resche et al. [72] Phase III | Sm-153 at 0.5 mCi/kg (55) vs. 1.0 mCi/kg (59) | Pain relief | Significant difference in pain scores between doses at wk 4 (p = 0.0476) | OS not different between groups | Mean leukocyte nadir and platelets lower with 1.0 mCi/kg than 0.5 mCi/kg | At wk 4, pain relief achieved in 55% for 0.5 mCi/kg and 70% with 1.0 mCi/kg |
Abbreviations: mos: months; OS: overall survival; wks: weeks: PSA-PFS: Prostate-specific antigen-progression-free survival.