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Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study

Nilsson, Sten; Franzen, Lars; Parker, Christopher; Tyrrell, Christopher; Blom, Rene; Tennvall, Jan LU ; Lennernas, Bo; Petersson, Ulf; Johannessen, Dag C. and Sokal, Michael, et al. (2007) In The Lancet Oncology 8(7). p.587-594
Abstract
Background The alpha-emitter radium-223 (Ra-223) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer. We aimed to study mature outcomes from a randomised, multicentre, phase II study of Ra-223. Methods Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of Ra-223 (50 kBq/kg, 33 patients) or placebo (31 patients), given every 4 weeks. Primary endpoints were change in bone-alkaline phosphatase (ALP) concentration and time to skeletal-related events (SREs). Secondary endpoints included toxic effects, time to prostate-specific-antigen (PSA) progression, and overall survival.... (More)
Background The alpha-emitter radium-223 (Ra-223) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer. We aimed to study mature outcomes from a randomised, multicentre, phase II study of Ra-223. Methods Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of Ra-223 (50 kBq/kg, 33 patients) or placebo (31 patients), given every 4 weeks. Primary endpoints were change in bone-alkaline phosphatase (ALP) concentration and time to skeletal-related events (SREs). Secondary endpoints included toxic effects, time to prostate-specific-antigen (PSA) progression, and overall survival. All tests were done at a 5% significance level, based on intention to treat. Findings Median relative change in bone-ALP during treatment was -65.6% (95% CI -69.5 to -57.7) and 9.3% (3.8-60.9) in the Ra-223 group and placebo groups, respectively (p<0.0001, Wilcoxon ranked-sums test). Hazard ratio for time to first SRE, adjusted for baseline covariates, was 1.75 (0.96-3.19, p=0.065, Cox regression). Haematological toxic effects did not differ significantly between two groups. No patient discontinued Ra-223 because of treatment toxicity. Median time to PSA progression was 26 weeks (16-39) versus 8 weeks (4-42; p=0.048) for Ra-223 versus placebo, respectively. Median overall survival was 65.3 weeks (48.7-infinity) for Ra-223 and 46.4 weeks (32.1-77.4) for placebo (p=0.066, log rank). The hazard ratio for overall survival, adjusted for baseline covariates was 2.12 (1.13-3.98, p=0.020, Cox regression). Interpretation Ra-223 was well tolerated with minimum myelotoxicity, and had a significant effect on bone-ALP concentrations. Larger clinical trials are warranted to study Ra-223 on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer. Bone-targeting properties of Ra-223 could also potentially be used for treating skeletal metastasis from other primary cancers. (Less)
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The Lancet Oncology
volume
8
issue
7
pages
587 - 594
publisher
Elsevier
external identifiers
  • wos:000248061500022
  • scopus:34347244905
ISSN
1474-5488
DOI
10.1016/S1470-2045(07)70147-X
language
English
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yes
id
0652b170-3b29-40d4-af31-e0bfe91bee64 (old id 645562)
date added to LUP
2007-12-18 17:28:03
date last changed
2017-11-05 03:28:47
@article{0652b170-3b29-40d4-af31-e0bfe91bee64,
  abstract     = {Background The alpha-emitter radium-223 (Ra-223) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer. We aimed to study mature outcomes from a randomised, multicentre, phase II study of Ra-223. Methods Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of Ra-223 (50 kBq/kg, 33 patients) or placebo (31 patients), given every 4 weeks. Primary endpoints were change in bone-alkaline phosphatase (ALP) concentration and time to skeletal-related events (SREs). Secondary endpoints included toxic effects, time to prostate-specific-antigen (PSA) progression, and overall survival. All tests were done at a 5% significance level, based on intention to treat. Findings Median relative change in bone-ALP during treatment was -65.6% (95% CI -69.5 to -57.7) and 9.3% (3.8-60.9) in the Ra-223 group and placebo groups, respectively (p&lt;0.0001, Wilcoxon ranked-sums test). Hazard ratio for time to first SRE, adjusted for baseline covariates, was 1.75 (0.96-3.19, p=0.065, Cox regression). Haematological toxic effects did not differ significantly between two groups. No patient discontinued Ra-223 because of treatment toxicity. Median time to PSA progression was 26 weeks (16-39) versus 8 weeks (4-42; p=0.048) for Ra-223 versus placebo, respectively. Median overall survival was 65.3 weeks (48.7-infinity) for Ra-223 and 46.4 weeks (32.1-77.4) for placebo (p=0.066, log rank). The hazard ratio for overall survival, adjusted for baseline covariates was 2.12 (1.13-3.98, p=0.020, Cox regression). Interpretation Ra-223 was well tolerated with minimum myelotoxicity, and had a significant effect on bone-ALP concentrations. Larger clinical trials are warranted to study Ra-223 on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer. Bone-targeting properties of Ra-223 could also potentially be used for treating skeletal metastasis from other primary cancers.},
  author       = {Nilsson, Sten and Franzen, Lars and Parker, Christopher and Tyrrell, Christopher and Blom, Rene and Tennvall, Jan and Lennernas, Bo and Petersson, Ulf and Johannessen, Dag C. and Sokal, Michael and Pigott, Katharine and Yachnin, Jeffrey and Garkavij, Michael and Strang, Peter and Harmenberg, Johan and Bolstad, Bjorg and Bruland, Oyvind S.},
  issn         = {1474-5488},
  language     = {eng},
  number       = {7},
  pages        = {587--594},
  publisher    = {Elsevier},
  series       = {The Lancet Oncology},
  title        = {Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study},
  url          = {http://dx.doi.org/10.1016/S1470-2045(07)70147-X},
  volume       = {8},
  year         = {2007},
}