Table 2.
Summary of trials of strontium-89 for metastatic prostate cancer.
| Study | Treatment description (# patients) | Primary endpoint | Results | Other outcomes | Adverse events | Comments |
|---|---|---|---|---|---|---|
| Pagliaro et al. [66] Phase I/II | Sr-89 with gemcitabine (4 patients received 600 mg/m2, 11 received 800 mg/m2) | PSA response | No patient achieved partial response (>80% reduction in PSA) | Overall survival (OS) 8 mos | Dose level 2 (neutropenia in 26.7%, thrombocytopenia 53.3%, anemia in 26.7%) | – |
| Laing et al. [53] Phase I/II | Sr-89 (83) | Pain response using non-standardized scale at 12 weeks | 75% with some pain relief and 22% pain-free | – | No grade-3/4 hematological adverse effects | Pain relief began in 6 weeks and lasting for 4–15 months |
| Buchali et al. [56] Phase I/II | Sr-89 (25) vs. placebo (24) | Pain response | 36.8% pain response in Sr-89 vs. 50% placebo | 2 year survival was 46% in Sr-89 vs. 4% placebo (p < 0.05) | Leukopenia, 12% in Sr-89 vs. 4.2% in placebo; thrombocytopenia, 50% in Sr-89 vs. 23.5% in placebo | – |
| Nilsson et al. [68] Phase II | Sr-89 (18) vs. 5-FU, epirubicin, mitomycin-C (17) | Pain response using a verbal scale | At 3 wks, pain reduced in both groups (p = 0.01 and 0.001 respectively) | No difference in Karnofsky performance status or analgesic use | More severe side-effects in chemotherapy group (p < 0.05) | – |
| Porteret al. [61] Phase III | Local XRT plus Sr-89 (68) vs. Local XRT plus placebo (58) | Pain response using RTOG criteria. Analgesic use. QoL using Visual analog scale | At 3 mos, complete pain relief 50% (Sr-89) vs. 36% (placebo); discontinuation of analgesics 17.1% (Sr-89) vs. 2.4% (placebo), p < 0.05 | Greater improvement in pain and physical activity with Sr-89 (p < 0.05); OS: 6.3 mos (Sr-89) vs. 7.9 mos (placebo), p = 0.6 | Leukopenia grade-3/4: 12% in Sr-89 vs. 0% in placebo; thrombocytopenia grade-3/4: 32.8% in Sr-89 vs. 3.4% in placebo | Time to further XRT 35.3 mos (Sr-89) vs. 20.3 mos (placebo), p = 0.006; # new painful sites 0.59 (Sr-89) vs. 1.21 (placebo), p < 0.002 |
| Turner et al. [48] Phase III | Sr-89 (93) | Pain response using RTOG criteria; QoL using FLIC index | At 3 mos, complete pain relief in 17.6% and some pain relief in 62.4% | At 3 mos, median increase of 12.8 points on FLIC index | Leukopenia grade ≥ 2: 12%; Thrombocytopenia grade ≥ 2: 22% | Patients with any pain response had improved QoL (p = 0.013) |
| Smeland et al. [62] Phase III | Sr-89 plus EBRT (46) vs. Placebo plus EBRT (49) | Progression of disease (using QLQ C-30 questionnaire, pain score, analgesic requirement, WHO performance status) | No difference in disease progression rates | No statistical difference in QoL index in the two groups; No difference in OS | Leukopenia grade-1/2: 36.4% in Sr-89 vs. 13.3% in placebo (p = 0.02); Thrombocytopenia grade-1/2: 15.9% in Sr-89 vs. 4.4% in placebo | – |
| Scuito et al. [67] Phase III | Sr-89 plus cisplatin (35) vs. Sr-89 plus placebo (35) | Pain response and duration of response | Pain response in 91% (Sr-89) vs. 63% (placebo), p < 0.01; duration of pain relief 120 d (Sr-89) vs. 60 d (placebo), p0.002 | OS: 9 mos (Sr-89) vs. 6 mos (placebo), p = 0.30 | Anemia grade-3/4: 8.5% in Sr-89 vs. 11.4%; leukopenia grade-1/2: 22.9% in Sr-89 vs. 5.7% in placebo; thrombocytopenia grade1/2: 2.8% in Sr-89 vs. 5.7% in placebo | Bone disease progression in 27% (Sr-89) vs. 64% (placebo), p = 0.01 |
| Quilty et al. [64] Phase III crossover | Sr-89 (76) vs. local XRT (72) Sr-89 (77) vs. hemibody XRT (80) | Pain response, mobility and analgesic use | At 3 mos, 65.1% patients with relief in pain with Sr-89 vs. 66.7% with local XRT; 70% in Sr-89 vs. 67.4% with hemibody XRT | OS: 33 wks (Sr-89) vs. 28 wks (XRT), p = 0.1 | Leukopenia grade-3: 3.1% in Sr-89 vs. 0% XRT; thrombocytopenia grade-3/4: 6.9% in Sr-89 vs. 3.4% in XRT | Fewer new painful sites after Sr-89 (p < 0.05) |
| Oosterhof et al. [63] Phase III | Sr-89 (101) vs. Local field XRT (102) | Subjective response using pain score, analgesic use or performance status | Subjective response in 34.7% of Sr-89 group vs. 33.3% of XRT | OS: 11 mos (XRT) vs. 7.2 mos (Sr-89), p = 0.0457 | No grade-3/4 leukopenia; 1 patient in Sr-89 with grade III toxicity | >50% decline in PSA in 13% with Sr-89 vs. 10% wiith XRT |
| Lewington et al. [55] Phase III crossover | Sr-89 vs. placebo (26) | Pain response | Complete pain response only in Sr-89; clinical response with Sr-89 better than placebo at first assessment (p < 0.01) and second assessment (p < 0.03) | – | Thrombocytopenia: grade- 3 toxicity in 12%, and grade-4 in 15.4% | – |
Abbreviations: d: days; FLIC: Functional Living Index Cancer Instrument; mos: months; OS: Overall survival; QoL: Quality of life; RTOG: Radiation Therapy Oncology Group; XRT: External radiation therapy.