***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Radium-223 dichloride ( radium-223 ) is the first targeted alpha therapy approved for the treatment of castration-resistant prostate cancer ( CRPC ) with bone metastases . This study investigated the efficacy and safety of radium-223 in Japanese patients with symptomatic CRPC and bone metastases . Methods In this open-label , multicenter , phase II study , patients with progressive , symptomatic CRPC and bone metastases were treated with radium-223 ( 55 kBq/kg , intravenously ) in a 4-week cycle for six cycles . The primary endpoint was the percent change in total alkaline phosphatase ( ALP ) from baseline at 12 weeks . Secondary endpoints included the percent ALP change from baseline to end of treatment ( EOT ) , ALP response rates , percent change in prostate-specific antigen ( PSA ) from baseline to 12 weeks and EOT , PSA response rates , overall survival ( OS ) , and time to symptomatic skeletal events ( SSEs ) . Adverse events were monitored throughout the study period . Results Of the 49 Japanese patients ( median age 74 years ) , 28 completed all infusions . Mean percent change in total ALP and PSA from baseline to 12 weeks was −19.3 and + 97.4 % , respectively . One-year OS and SSE-free rate at the end of active follow-up were 78 and 89 % , respectively . The ALP response rate was 31 % , while the PSA response rate was 6 % . Grade 3/4 treatment-emergent adverse events observed in ≥10 % of patients included decreased lymphocyte count ( 14 % ) , anemia ( 14 % ) , anorexia ( 10 % ) , and bone pain ( 10 % ) . Conclusions Radium-223 is effective and well tolerated in Japanese patients with CRPC and bone metastases . Results were comparable with the Alpharadin in Symptomatic Prostate Cancer Patients ( ALSYMPCA ) trial . Clinical trial registration Clinical Trials.gov NCT01929655 Background Multiple castration‐resistant prostate cancer ( CRPC ) therapies are approved by the United States Food and Drug Administration . Radium‐223 dichloride ( Ra‐223 ) with abiraterone acetate plus prednisone have different mechanisms of action and distinct off‐target side‐effect profiles . We prospect ively investigated their combined safety , tolerability , and patient‐reported outcome measures . Patients and Methods eRADicAte , an investigator‐initiated , phase II trial , studied 31 patients with metastatic CRPC , from 5 United States uro‐oncology research sites . Patients completed 6 cycles of Ra‐223 with concurrent abiraterone therapy .  Quality of life and pain were assessed using the Functional Assessment of Cancer Therapy‐Prostate and the Brief Pain Inventory‐Short Form question naires and their subscales ; we reported the number of subjects meeting st and ardized criteria for clinical ly meaningful improvements on each scale . Safety assessment included Eastern Cooperative Oncology Group performance status , laboratory changes , opioid use , radiographic responses , and adverse events ( AEs ) . Results Twenty of 31 ( 65 % ) experienced positive clinical ly meaningful improvement changes on the Functional Assessment of Cancer Therapy‐Prostate , and 25 ( 81 % ) of 31 on the Prostate Cancer Subscale . Eighteen ( 58 % ) of 31 demonstrated reduced pain intensity and 12 ( 39 % ) of 31 demonstrated reduction of pain interference in their lives . At baseline , subjects averaged 11.6 ± 2.8 bone lesions ; at the end of treatment , subjects averaged 5.6 ± 2.4 bone lesions ( P = .0002 ) . The most frequent AEs were diarrhea ( 17 % ) , nausea ( 17 % ) , and fatigue ( 14 % ) . There were 6 serious AEs ; 1 led to study withdrawal . Conclusions Patients experienced clinical ly meaningful improvements in quality of life and pain , without unexpected adverse toxicities . Phase III combination trials of Ra‐223 with novel oral hormonal agents are ongoing to further evaluate radiographic progression and overall survival benefit . Micro‐ Abstract This is the first study to prospect ively evaluate the combined use of radium‐223 dichloride and a novel oral hormonal therapy , abiraterone acetate , in men with metastatic castration‐resistant prostate cancer . The eRADicAte study showed that patients with metastatic castration‐resistant prostate cancer experienced clinical ly meaningful improvements in quality of life with decreased pain , reduction in bone lesions , and an acceptable safety and toxicity profile Purpose / Objectives : Radium-223 is a first-in-class radiopharmaceutical recently approved for the treatment of castration-resistant prostate cancer in patients with symptomatic bone metastases . Initial studies investigating Radium-223 primarily used nonsteroidal first-generation anti and rogens . Since that time , newer anti and rogen therapies have demonstrated improved survival in patients with castration-resistant prostate cancer . It has been suggested that the rational combination of these newly approved agents with Radium-223 may lead to improved response rates and clinical outcomes . Currently , there is lack of information regarding the safety of concurrent administration of these agents with radiopharmaceuticals . Here , we report on hematologic toxicity findings from our institution in patients receiving concurrent Radium-223 and next-generation anti and rogen therapies with either enzalutamide or abiraterone . Material s/ Methods : In a retrospective study , we analyzed patients who received Radium-223 as part of an early-access trial , and following FDA approval in May 2013 , patients receiving Radium-223 as part of st and ard care . Radium-223 was given at st and ard dosing of 50 kBq/kg each month for 6 total cycles . Complete blood counts were performed before treatment monthly and following each injection . Blood counts from patients receiving Radium alone and concurrently with next-generation anti and rogens were compared . To date , 25 total patients were analyzed , with a median of 5 monthly doses received per patient . Fourteen patients received concurrent therapy during monthly Radium-223 with either enzalutamide ( n=8 ) or abiraterone ( n=6 ) . Results : Six patients expired due to disease progression . Two patients discontinued treatment due to grade 3 myelosuppression . For patients receiving either Radium alone and with concurrent next-generation anti and rogen therapy , there did not appear to be any statistically significant differences between initial and nadir blood counts . Mean change from initial neutrophil count to nadir was 1.9 × 106/L in patients receiving Radium alone , versus 2.3 × 106/L in patients receiving concurrent therapy ( P=0.77 ) . Mean change from initial hemoglobin value to nadir was 1.5 g/L in patients receiving Radium alone , versus 1.8 g/L in patients receiving concurrent therapy ( P=0.31 ) . Mean change from initial platelet count to nadir was 52.3 × 109 cells/L in patients receiving Radium alone versus 70.6 × 109 cells/L in patients receiving concurrent therapy ( P=0.39 ) . Individual blood counts for each measured laboratory are included in the supplemental data . PSA was stable or decreased in 22 % of patients receiving Radium alone versus 35 % of patients receiving combination treatment ( P=0.24 ) . Conclusions : Concurrent administration of Radium-223 and next-generation anti and rogen therapies appears to be well tolerated with similar toxicities to st and ard administration of Radium-223 alone . This particular cohort of patients represents a high-risk , heavily pretreated group of patients with advanced metastatic disease and significant marrow burden . Despite these risk factors , hematologic toxicity was modest and was in the range expected for this risk group based on previous trials . To date , this is the first study investigating the toxicity of combination treatment . Further studies investigating the safety and efficacy of combination treatments are warranted BACKGROUND The alpha-emitter radium-223 ( (223)Ra ) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer . We aim ed to study mature outcomes from a r and omised , multicentre , phase II study of (223)Ra . METHODS Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy  were assigned to four intravenous injections of (223)Ra ( 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 (223)Ra 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 (223)Ra because of treatment toxicity . Median time to PSA progression was 26 weeks ( 16 - 39 ) versus 8 weeks ( 4 - 12 ; p=0.048 ) for (223)Ra versus placebo , respectively . Median overall survival was 65.3 weeks ( 48.7-infinity ) for (223)Ra 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 (223)Ra was well tolerated with minimum myelotoxicity , and had a significant effect on bone-ALP concentrations . Larger clinical trials are warranted to study (223)Ra on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer . Bone-targeting properties of (223)Ra could also potentially be used for treating skeletal metastasis from other primary cancers Radium-223 dichloride ( radium-223 ) mimics calcium and emits high-energy , short-range alpha-particles result ing in an antitumor effect on bone metastases . This open-label , phase IIa nonr and omized study investigated safety and short-term efficacy of radium-223 in breast cancer patients with bone-dominant disease . Twenty-three advanced breast cancer patients with progressive bone-dominant disease , and no longer c and i date s for further endocrine therapy , were to receive radium-223 ( 50 kBq/kg IV ) every 4 weeks for 4 cycles . The co primary end points were change in urinary N-telopeptide of type 1 ( uNTX-1 ) and serum bone alkaline phosphatase ( bALP ) after 16 weeks of treatment . Exploratory end points included sequential 18F-fluorodeoxyglucose positron emission tomography and computed tomography ( FDG PET/CT ) to assess metabolic changes in osteoblastic bone metastases . Safety data were collected for all patients . Radium-223 significantly reduced uNTX-1 and bALP from baseline to end of treatment . Median uNTX-1 change was −10.1 nmol bone collagen equivalents/mmol creatinine ( −32.8 % ; P = 0.0124 ) ; median bALP change was −16.7 ng/mL ( −42.0 % ; P = 0.0045 ) . Twenty of twenty-three patients had FDG PET/CT identifying 155 hypermetabolic osteoblastic bone lesions at baseline : 50 lesions showed metabolic decrease ( ≥25 % reduction of maximum st and ardized uptake value from baseline ) after 2 radium-223 injections [ 32.3 % metabolic response rate ( mRR ) at week 9 ] , persisting after the treatment period ( 41.5 % mRR at week 17 ) . Radium-223 was safe and well tolerated . Radium-223 targets areas of increased bone metabolism and shows biological activity in advanced breast cancer patients with bone-dominant disease PURPOSE Study distribution , pharmacokinetics , and safety of intraperitoneal ( IP ) 212Pb-TCMC-trastuzumab in patients with HER-2-expressing malignancy . EXPERIMENTAL DESIGN IP 212Pb-TCMC-trastuzumab was delivered , after 4 mg/kg intravenous ( IV ) trastuzumab , to 3 patients with HER-2-expressing cancer who had failed st and ard therapies . Patients were monitored for toxicity and pharmacokinetics/dosimetry parameters . RESULTS Imaging studies after 0.2 mCi/m2 
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In clinical trials in mCRPC , 223RaCl2 monotherapy is well tolerated , with significantly longer overall survival than placebo and improved quality of life .
Clinical trial data have been reinforced by findings from real-world studies .
223RaCl2 has also shown promise in other tumour types with bone metastases , including advanced breast cancer and advanced renal cell carcinoma ( in combination with anti-vascular endothelial growth factor ) .
Several astatine-211- and bismuth-213-labelled molecules have demonstrated anti-tumour activity and acceptable toxicity in other tumour types .
Conclusions 223RaCl2 has demonstrated “ proof of concept ” for use of TAT in cancer in clinical practice .