Clinical experience with radium-223 in the treatment of patients with advanced castrate-resistant prostate cancer and symptomatic bone metastases

Hague, Christina; Logue, John P

doi:10.1177/1756287216629870

Cited by 19 publications

(15 citation statements)

References 15 publications

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“…The overall median survival of 10.5 months for Ra-223 patients observed here is inferior to that reported for both the Ra-223 and the placebo groups (14.9 vs. 11.3) in the ALSYMPCA trial. Other real world retrospective studies have reported median overall survival ranging from 8.3 months to 12.9 months [7][8][9], in-keeping with that observed in this cohort.…”

Section: Discussionsupporting

confidence: 90%

Real-world Outcomes and Factors Predicting Survival and Completion of Radium 223 in Metastatic Castrate-resistant Prostate Cancer

et al. 2018

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Section: Discussionsupporting

confidence: 90%

Real-world Outcomes and Factors Predicting Survival and Completion of Radium 223 in Metastatic Castrate-resistant Prostate Cancer

et al. 2018

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“…The advanced extent of disease of the study population could have been the reason for the high incidence of hematologic toxicity relative to that in the existing literature (14,(24)(25)(26). In particular, thrombocytopenia was frequent and was associated with a complete lack of recovery within 6 mo despite the discontinuation of 223 RaCl 2 .…”

Section: Discussionmentioning

confidence: 95%

²²³Ra Therapy of Advanced Metastatic Castration-Resistant Prostate Cancer: Quantitative Assessment of Skeletal Tumor Burden for Prognostication of Clinical Outcome and Hematologic Toxicity

et al. 2017

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The aim of this study was to investigate the prognostic value of the quantitative assessment of skeletal tumor burden on bone scintigraphy (Bone Scan Index [BSI]) in patients who have advanced metastatic castration-resistant prostate cancer (mCRPC) and are receiving RaCl We hypothesized that the BSI can serve as a prognostic biomarker of overall survival (OS) and hematologic toxicity and as a tool for response assessment in patients with mCRPC treated with RaCl This study was a retrospective investigation of a Danish cohort of mCRPC patients who received RaCl therapy between March 2014 and October 2015 and for whom baseline bone scintigraphy was available. Bone scintigraphy studies were reviewed and graded according to the extent of disease. Furthermore, an automated BSI (EXINI Bone) was obtained for baseline scintigraphy studies and follow-up scans after 3 cycles as well as at the end of therapy. Clinical outcomes were OS and occurrence of hematologic toxicity of grades 2-5. Associations between the BSI and clinical outcomes were investigated in multivariate regression models including the visual assessment of bone scintigraphy and other relevant covariates. A total of 88 patients were included. The median number of completedRaCl cycles was 4, and 27 patients (31%) completed 6 cycles. The BSI was significantly associated with OS in the multivariate analysis; the median OS for patients with a BSI of greater than 5 was 8.2 mo, and the median OS for patients with a BSI of less than or equal to 5 was 15.0 mo (hazard ratio, 2.65 [95% confidence interval, 1.5-4.71]; = 0.001). Likewise, the baseline BSI was prognostic for the occurrence of hematologic toxicity; patients with a BSI of greater than 5 had an odds ratio of 3.02 (95% confidence interval, 1.2-7.8; = 0.02) for toxicity. The BSI declined during therapy in 44% of the patients who completed 3 cycles of RaCl ( = 52) and in 84% of the patients after the end of therapy ( = 32). There was no significant association between a change in the BSI during therapy and OS. The BSI is a promising biomarker for prognostication of OS and hematologic toxicity in late-stage mCRPC patients receivingRaCl Further prospective studies are needed to evaluate the potential of the BSI for response assessment in RaCl therapy.

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“…223 Ra-Dichloride is a targeted alpha-emitter therapy that mimics calcium and targets areas of increased bone turnover. Alpha particles have a very short range (<100 μm), so damage to surrounding tissues is minimal [ 9 ]. Prior to the introduction of 223 Ra-dichloride, bone-targeting therapies did not lead to longer overall survival (OS); the benefits were primarily limited to pain relief and delay of skeletal events [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

223Ra-Dichloride in castration-resistant metastatic prostate cancer: improving outcomes and identifying predictors of survival in clinical practice

Dizdarevic

Jessop

Begley

et al. 2018

Eur J Nucl Med Mol Imaging

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PurposeWe first assessed whether the pattern of referrals to a nuclear medicine clinic improved as experience with 223Ra-dichloride increased, and whether referral patterns affected patient outcomes, and second assessed the value of bone scintigraphy, total alkaline phosphatase (tALP) and lymphadenopathy as prognostic factors in patients receiving 223Ra-dichloride.MethodsA total of 57 patients eligible to receive 223Ra-dichloride over a 2-year period (March 2014 to March 2016) were retrospectively assessed and prospectively followed (median follow up 298 days). 223Ra-Dichloride was administered at 4-week intervals for a maximum of six injections. The numbers of patients in years 1 and 2 referred in relation to extent of bone disease (EOBD) category and overall survival (OS) were determined. The prognostic factors EOBD category, baseline tALP (tALPBL), tALP response, greatest percentage reduction in tALP from baseline in any treatment cycle (ALPmax; among patients with elevated ALPBL), and the presence of lymphadenopathy were assessed as predictors of OS.ResultsThe proportion of patients with EOBD1 was higher in year 2 than in year 1 (29% and 4%, respectively), and in year 2 there was a lower rate of symptomatic skeleton-related events, a higher proportion of patients completing six cycles, and longer (albeit nonsignificant) OS (p = 0.55). There were significant differences in OS between EOBD4 patients and those in all other groups and between EOBD1 and EOBD3 patients (p < 0.05). OS was longer in patients with normal tALPBL than in those with elevated tALPBL (p = 0.01), in ALP responders than in nonresponders (p < 0.05), and in patients without lymphadenopathy than in those with lymphadenopathy (p = 0.29). OS was correlated with ALPmax (r2 = 0.24).ConclusionA collaborative multidisciplinary referrals pathway, together with increased experience with 223Ra-dichloride, led to improved outcomes. In patients with elevated tALPBL, tALP dynamics may be useful for monitoring response and predicting OS. Imaging and prognostic markers may therefore be of value for individualizing 223Ra-dichloride treatment and planning retreatment; however, further studies are required.

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Clinical experience with radium-223 in the treatment of patients with advanced castrate-resistant prostate cancer and symptomatic bone metastases

Cited by 19 publications

References 15 publications

Real-world Outcomes and Factors Predicting Survival and Completion of Radium 223 in Metastatic Castrate-resistant Prostate Cancer

Real-world Outcomes and Factors Predicting Survival and Completion of Radium 223 in Metastatic Castrate-resistant Prostate Cancer

²²³Ra Therapy of Advanced Metastatic Castration-Resistant Prostate Cancer: Quantitative Assessment of Skeletal Tumor Burden for Prognostication of Clinical Outcome and Hematologic Toxicity

223Ra-Dichloride in castration-resistant metastatic prostate cancer: improving outcomes and identifying predictors of survival in clinical practice

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Clinical experience with radium-223 in the treatment of patients with advanced castrate-resistant prostate cancer and symptomatic bone metastases

Cited by 19 publications

References 15 publications

Real-world Outcomes and Factors Predicting Survival and Completion of Radium 223 in Metastatic Castrate-resistant Prostate Cancer

Real-world Outcomes and Factors Predicting Survival and Completion of Radium 223 in Metastatic Castrate-resistant Prostate Cancer

223Ra Therapy of Advanced Metastatic Castration-Resistant Prostate Cancer: Quantitative Assessment of Skeletal Tumor Burden for Prognostication of Clinical Outcome and Hematologic Toxicity

223Ra-Dichloride in castration-resistant metastatic prostate cancer: improving outcomes and identifying predictors of survival in clinical practice

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²²³Ra Therapy of Advanced Metastatic Castration-Resistant Prostate Cancer: Quantitative Assessment of Skeletal Tumor Burden for Prognostication of Clinical Outcome and Hematologic Toxicity