Two-Year Survival Follow-Up of the Randomized, Double-Blind, Placebo-Controlled Phase II Study of Radium-223 Chloride in Patients With Castration-Resistant Prostate Cancer and Bone Metastases

Nilsson, Sten; Franzén, Lars; Parker, Christopher; Tyrrell, C.J.; Blom, René; Tennvall, Jan; Lennernäs, Bo; Petersson, Ulf; Johannessen, Dag Clement; Sokal, M.; Pigott, K.; O'Bryan-Tear, C. Gillies; Thuresson, Marcus; Bolstad, B.; Bruland, Øyvind S.

doi:10.1016/j.clgc.2012.07.002

Cited by 100 publications

(96 citation statements)

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“…The high linear energy transfer of α particles has been associated with greater biological effectiveness than that of β− particles (Pandit-Taskar et al 2014;Harrison et al 2013;Nilsson et al 2013). 223 Ra-dichloride has been shown to not only have a palliative effect but also a survival prolonging effect (Harrison et al 2013;Nilsson et al 2013).…”

Section: < Figure 5 Should Be Inserted Around Here > IV Discussion Amentioning

confidence: 99%

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Computational modeling of radiobiological effects in bone metastases for different radionuclides

Liberal

Tavares

2017

International Journal of Radiation Biology

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Purpose: Computational simulation is a simple and practical way to study and to compare a variety of radioisotopes for different medical applications, including the palliative treatment of bone metastases. This study aimed to evaluate and compare cellular effects modelled for different radioisotopes currently in use or under research for treatment of bone metastases using computational methods. Methods:Computational models were used to estimate the radiation-induced cellular effects (Virtual Conclusions:223 Ra alpha particles induced the highest cell death of all investigated particles on metastatic prostate cells in comparison to irradiation with β − radionuclides, two of the most frequently used radionuclides in the palliative treatment of bone metastases in clinical routine practice. Moreover, the data obtained suggest that the used computational methods might provide some perception about cellular effects following irradiation with different radionuclides.

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Section: < Figure 5 Should Be Inserted Around Here > IV Discussion Amentioning

confidence: 99%

“…Furthermore, typically α emitters induce less hematologic toxicity for a given bone surface dose than β − emitters (Pandit-Taskar et al 2014;Harrison et al 2013;Nilsson et al 2013). …”

Section: < Figure 5 Should Be Inserted Around Here > IV Discussion Amentioning

confidence: 99%

Computational modeling of radiobiological effects in bone metastases for different radionuclides

Liberal

Tavares

2017

International Journal of Radiation Biology

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“…223 Ra α particle emission is an appealing strategy for the treatment of bone micrometastases, owing to the short tissue range penetration associated with these radioactive particles that can allow for a more circumscribed irradiation surface. Consequently, α emitters induce typically less hematologic toxicity for a given bone surface dose than β -emitters (Harrison et al, 2013;Nilsson et al, 2013b;PanditTaskar et al, 2014). Furthermore, the high LET of α particles has been associated with greater biological effectiveness than β -particles (Harrison et al, 2013;Nilsson et al, 2013b;PanditTaskar et al, 2014).…”

Section: Iij Radium-223mentioning

confidence: 99%

“…223 RaCl 2 (Xofigo TM , Bayer Pharmaceuticals) is the first alpha particle-emitting radiopharmaceutical approved for routine clinical use by the FDA (Harrison et al, 2013). To date, 223 Ra-dicloride is the only radiopharmaceutical identified for treatment of palliative bone metastasis with shown ability to increase patients' life-expectancy (Harrison et al, 2013;Nilsson et al, 2013a).…”

Section: Iiii 223 Ra-chloridementioning

confidence: 99%

“…For example, the decay of 125 I has been shown to lead to the deposition of a very high dose (≈10 9 cGy/decaying atom) in the immediate vicinity (≈2 nm 3 ) of the decay site and a sharp and significant drop in the energy deposited (from ≈10 9 to ≈10 6 cGy) as a function of increasing distance (few nanometres) from the decaying 125 I atom (Kassis, 2011). For example, when 125 I is localized within the cytoplasm, the survival curve is of the low LET type and the number of decays needed to reduce survival is ≈80 times that of DNA-incorporated 125 I (Kassis, 2011 (Abbasi, 2012(Abbasi, , 2011Argyrou et al, 2013a;Bączyk, 2011;Bryan et al, 2009;Chakraborty et al, 2008;Daha et al, 2010;Das et al, 2009;Harrison et al, 2013;Lewington, 2005;Máthé et al, 2010;Neves et al, 2005;Nilsson et al, 2013bNilsson et al, , 2007Nilsson et al, , 2005aNilsson et al, , 2005bPandit-Taskar et al, 2014;Ramdahl et al, 2013;Sartor, 2004;Simón et al, 2012;Sivaprasad and Rajagopal, 2012;Tomblyn, 2012;Vigna et al, 2011;Volkert and Hoffman, 1999;Wang et al, 2011). Despite the growing number of radionuclides investigated for treatment of bone metastases, the use of 89 Sr and 153 Sm still accounts for the bulk of radiopharmaceutical bonetargeted therapeutics in the clinical context and the majority of the review articles available in the literature focus on those two radionuclides.…”

Section: Introductionmentioning

confidence: 99%

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Palliative treatment of metastatic bone pain with radiopharmaceuticals: A perspective beyond Strontium-89 and Samarium-153

Liberal

Tavares

2016

Applied Radiation and Isotopes

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Purpose: The present review article aims to provide an overview of the available radionuclides for palliative treatment of bone metastases beyond 89 Sr and 153 Sm. In addition, it aims to review and summarize the clinical outcomes associated with the palliative treatment of bone metastases using different radiopharmaceuticals. Materials and Methods: A literature search was conducted on Science Direct and PubMed databases (1990 -2015). The following search terms were combined in order to obtain relevant results: "bone", "metastases", "palliative", "care", "therapy", "treatment", "radiotherapy", "review", "radiopharmaceutical", "phosphorus-32", "strontium-89", "yttrium-90", "tin-117m", "samarium-153", "holmium-166", "thulium-170", "lutetium-177", "rhenium-186", "rhenium-188" and "radium-223". Studies were included if they provided information regarding the clinical outcomes. Results and Conclusions: A comparative analysis of the measured therapeutic response of different radiopharmaceuticals, based on previously published data, suggests that there is a lack of substantial differences in palliative efficacy among radiopharmaceuticals. However, when the comparative analysis adds factors such as patient's life expectancy, radionuclides' physical characteristics (e.g. tissue penetration range and half-life) and health economics to guide the rational selection of a radiopharmaceutical for palliative treatment of bone metastases, 177 Lu and 188 Re-labeled radiopharmaceuticals appear to be the most suitable radiopharmaceuticals for treatment of small and medium/large size bone lesions, respectively.

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Clinical outcomes and survival surrogacy studies of prostate‐specific antigen declines following enzalutamide in men with metastatic castration‐resistant prostate cancer previously treated with docetaxel

Armstrong

Saad

Phung

et al. 2017

Cancer

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BACKGROUNDIn the AFFIRM trial, enzalutamide significantly increased overall survival (OS) for men with metastatic castration‐resistant prostate cancer (mCRPC) after chemotherapy versus placebo and significantly decreased prostate‐specific antigen (PSA) levels. The goal of this post hoc analysis was to associate levels of PSA decline from baseline after enzalutamide with clinical outcomes in the postchemotherapy mCRPC setting.METHODSMen in the AFFIRM trial (n = 1199) were grouped by maximal PSA decline in the first 90 days of treatment. Kaplan‐Meier estimates evaluated the association of defined PSA changes from baseline with OS, progression‐free survival (PFS), radiographic PFS (rPFS), and pain response. Each PSA decline category was assessed for OS surrogacy using Prentice criteria, proportion of treatment effect explained (PTE), and proportion of variation explained.RESULTSMen treated with enzalutamide had improved OS (hazard ratio, 0.63; P < .001) and higher rates of PSA decline (odds ratio, >19.0; P < .001) versus placebo. PSA declines of any, ≥30%, ≥50%, and ≥90% with enzalutamide were strongly associated with greater OS, PSA PFS, rPFS (P < .001), and pain response (P < .026) versus PSA increase/no decline. Any, ≥30%, and ≥50% declines in PSA resulted in the PTE range of 1.07‐1.29, where treatment was no longer significant after adjustment for decline measures (P > .20).CONCLUSIONSPSA declines of any, ≥30%, and ≥50% following enzalutamide were associated with greater clinical and pain response and improvements in PFS and OS. Surrogacy of PSA decline for OS was not fully established, possibly due to lack of PSA declines with placebo, and discordant results between PSA and imaging responses over time, and because some declines were not durable due to rapid resistance development. However, a lack of PSA decline by 90 days following enzalutamide treatment was a poor prognosis indicator in this setting. Conclusions from sensitivity analyses of maximal PSA decline from baseline over the entire treatment period are consistent with PSA declines restricted to the first 90 days. Cancer 2017;123:2303–2311. © 2017 American Cancer Society.

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Two-Year Survival Follow-Up of the Randomized, Double-Blind, Placebo-Controlled Phase II Study of Radium-223 Chloride in Patients With Castration-Resistant Prostate Cancer and Bone Metastases

Cited by 100 publications

References 24 publications

Computational modeling of radiobiological effects in bone metastases for different radionuclides

Computational modeling of radiobiological effects in bone metastases for different radionuclides

Palliative treatment of metastatic bone pain with radiopharmaceuticals: A perspective beyond Strontium-89 and Samarium-153

Clinical outcomes and survival surrogacy studies of prostate‐specific antigen declines following enzalutamide in men with metastatic castration‐resistant prostate cancer previously treated with docetaxel

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