Radium-223 in metastatic castration resistant prostate cancer: Progression free survival and pain scores—Real-world single-institution experience.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 250-250
Author(s):  
Amarnath Challapalli ◽  
Serena Hilman ◽  
Sue Cowley ◽  
Susan Masson ◽  
Dorothy Grifiths ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Serum Alkaline Phosphatase ◽  
Progression Free Survival ◽  
Discontinuation Rate ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Pain Scores ◽  
Radium 223

250 Background: Radium-223 (Ra223) is a novel alpha-emitting radiopharmaceutical agent approved for use in patients with metastatic castration resistant prostate cancer (mCRPC) and bone metastases based on ALSYMPCA results. We report our early experience in this setting. Methods: 36 patients were treated with Ra223 from Feb 2014 - Aug 2015. The patients were planned to receive 6 injections at a dose of 50 kBq/kg every 4 weekly. The pain was assessed using the visual analogue score (VAS). The effect of 6 cycles of Ra223 on blood counts, serum alkaline phosphatase (SAP), PSA, VAS and progression free survival (PFS) were evaluated. Results: At baseline (BL) median age was 79years; 66% of patients were ECOG 0-1; median VAS was 6. 53% had received prior docetaxel. 18 patients (50%) received all the scheduled 6 cycles of Ra223. In these patients there was a significant reduction in the pain scores both after the first cycle and after 6 cycles compared to the BL score (p < 0.05 & p < 0.001, respectively). A 30% reduction in the SAP levels was seen (p = 0.03). The reduction in pain scores was independent of the PSA response. The treatment was well tolerated with no grade 3,4 toxicity. Discontinuation rate was 50% (18/36) and was due to disease progression. Prior docetaxel use was associated with a higher discontinuation rate (12/18), as was albumin level < 34g/dL (60% vs. 43%). 7 (19%) required blood transfusions during the course. The median PFS was 6.1 months. It was significantly longer in those who completed 6 cycles of treatment and in patients with SAP < 220 U/L (10.97vs.5.2 & 10.33vs.6.4 months, respectively: p < 0.0001). There was a non-significant trend towards longer PFS in patients who had no prior docetaxel (10.33vs.6.5m; p = 0.05) and in patients with Albumin > 34 (8.9vs.6.4m; p = 0.06). Conclusions: Ra223 is a safe and effective treatment for mCRPC with bone metastases. Completion of 6 cycles is associated with a significantly better PFS, reduction in pain scores and in SAP levels. Prior docetaxel use and lower albumin levels were associated with a higher discontinuation rate and this should be considered in the decision process for optimising therapy sequencing.

Radium-223 in metastatic castration-resistant prostate cancer: Effect of performance score and albumin levels.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e594-e594
Author(s):  
Amarnath Challapalli ◽  
Sue Cowley ◽  
Dorothy Griffiths ◽  
Eleanor Compton ◽  
Rajendra Persad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Serum Alkaline Phosphatase ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Performance Score ◽  
Castration Resistant ◽  
Pain Scores ◽  
Radium 223 ◽  
Ecog Ps

e594 Background: Radium-223 (Ra223) is a novel alpha-emitting radiopharmaceutical agent approved for use in patients with metastatic castration resistant prostate cancer (mCRPC) and bone metastases based on ALSYMPCA results. However, its optimal sequencing in the treatment of mCRPC remains unclear. We evaluated the relevance of albumin (A) levels to aid in optimal selection and timing for Ra223 treatment. Methods: Eighty-eight patients had completed treatment with Ra223 from Feb 2014 - Sep 2016. The patients were planned to receive 6 injections at a dose of 55 kBq/kg every 4 weeks. Visual analogue score (VAS) was used to assess pain. The effect of serum alkaline phosphatase (SAP), docetaxel chemotherapy, A levels and performance score (ECOG-PS) on progression free survival (PFS) and overall survival (OS) were evaluated. Results: At baseline (BL) median age was 74.5years; 68% of patients were ECOG-PS-0/1; median VAS was 4.5 & median A level was 34g/dL. 48% had received prior docetaxel. 45 patients (51%) received all the scheduled 6 cycles with significant reduction in the pain scores after 6 cycles compared to the BL score (p < 0.05). The reduction in pain scores was independent of the PSA response and ECOG-PS. A 34% reduction in the SAP levels was seen (p = 0.003). The treatment was well tolerated with no grade 3,4 toxicity. Discontinuation rate was 49% (43/88) due to disease progression. In PS-0/1 patients who completed 6 cycles, PFS & OS were significantly longer compared to those who didn't (7.8vs.4.2& 21vs.7.6 months, respectively). Patients with SAP ≤ 220 U/L & A ≥ 34 g/dL also had significantly prolonged OS (16.2vs.8.6 & 16.1vs.9.5 months, respectively). Patients with PS-2/3 also had significantly longer PFS and OS with completion of 6 cycles and prolonged OS with SAP ≤ 220 U/L, but not with A levels. Conclusions: Ra223 is a safe and effective treatment for mCRPC with bone metastases. Completion of 6 cycles improved outcome. Lower SAP and high A levels significantly prolonged OS in PS-1/2 patients. Whilst the level of SAP can be a reflection of disease activity, monitoring A levels and ensuring that Ra223 is started before A level goes below 34, especially in PS-1/2 patients will aid in the benefit from this treatment in mCRPC.

Correlation of 18F-fluoride PET response to dasatinib in castration-resistant prostate cancer bone metastases with progression-free survival: Preliminary results from ACRIN 6687.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5003-5003
Author(s):  
Evan Y. Yu ◽  
Fenghai Duan ◽  
Mark Muzi ◽  
Jeremy Gorelick ◽  
Bennett Chin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Pet Imaging ◽  
Progression Free Survival ◽  
Post Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Normal Bone ◽  
Castration Resistant ◽  
Pre Treatment

5003 Background: Dasatinib is a SRC kinase inhibitor that decreases bone turnover in men with metastatic castration-resistant prostate cancer (mCRPC). 18F-fluoride PET was used to evaluate differential response between normal and tumor bone to dasatinib. Methods: Patients with bone mCRPC underwent dynamic 18F-flouride PET imaging prior to and 12 weeks after dasatinib treatment. Up to 5 bone metastases with matching normal bone regions were selected for analysis by SUVmax, Ki, K1and Patlak flux. Their pre-treatment values and change from pre-treatment to post-treatment values were evaluated via generalized estimating equations to predict skeletal-related events (SRE) and via Cox proportional hazards modeling to predict progression-free survival (PFS) with Prostate Cancer Working Group 2 criteria, overall survival and time to SRE. Results: Eighteen patients treated with dasatinib underwent baseline 18F-flouride PET imaging; 12 had follow-up scans allowing assessment of changes due to therapy. Median age for all patients was 69 (range 48-86) years. Significant decrease in SUVmax (p=0.0002) occurred in bone metastases with dasatinib while significant increases in Patlak flux (p=0.0033) occurred in normal bone. Significant differences in changes from tumor bone compared to normal bone in response to dasatinib were noted for SUVmax (p<0.0001). Of 18 patients, 17 have either met progression criteria or death by the time of this analysis. Decrease in tumor bone SUVmax (p=0.019), Ki(p=0.022), and Patlak flux (p=0.034) from pre-treatment to post-treatment correlates with longer PFS. Conclusions: 18F-fluoride PET indicates differential effect of dasatinib on tumor compared to normal bone in men with mCRPC. In patients undergoing pre- and post-dasatinib 18F-fluoride PET imaging a decrease in bone mCRPC fluoride uptake in response to treatment correlates with PFS. Clinical trial information: NCT00936975.

scholarly journals Interim and end-treatment 18F-Fluorocholine PET/CT and bone scan in prostate cancer patients treated with Radium 223 dichloride

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ana María García Vicente ◽  
Mariano Amo-Salas ◽  
Javier Cassinello Espinosa ◽  
Roberto Gómez Díaz ◽  
Ángel Soriano Castrejón
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Therapeutic Failure ◽  
Castration Resistant Prostate Cancer ◽  
Clinical Progression ◽  
Free Survival ◽  
Castration Resistant ◽  
Radium 223 ◽  
Pet Ct ◽  
Biochemical Progression

AbstractTo assess the predictive and prognostic aim of interim and end-treatment 18F-fluorocholine PET/CT (FCH-PET/CT) and 99mTc-methilen diphosphonate bone scintigraphy (BS) in patients with castration-resistant prostate cancer and bone metastases (CRPC-BM) treated with Radium 223 dichloride (223Ra). Prospective and multicentre ChoPET-Rad study including 82 patients with CRPC-BM. Baseline, after 3 (interim) and 6 doses (end-treatment) BS and FCH PET/CT were performed in patients who meet the study criteria. Clinical variables, imaging and clinical progression were obtained and their association with progression free survival (PFS), and overall survival (OS) was studied. Agreement between BS and FCH PET/CT response was assessed using Kappa (K) analysis. Median of PFS and OS was 3 and 16 months, respectively. Agreement between interim BS and FCH PET/CT was weak (K: 0.28; p = 0.004). No agreement was observed between end-treatment diagnostic studies. Interim and end-treatment FCH PET/CT were related to PFS (p = 0.011 and p < 0.001, respectively). Therapeutic failure and interim BS and FCH PET/CT showed association with OS (p < 0.001, p = 0.037 and p = 0.008, respectively). Interim and end-treatment FCH PET/CT were good predictors of biochemical progression in patients treated with 223Ra. Therapeutic failure and progression in interim BS or FCH PET/CT were adverse factors for OS.

scholarly journals A real-world evaluation of radium-223 in combination with abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253021
Author(s):  
Stephanie I. Kim ◽  
Andy H. Szeto ◽  
Katherine P. Morgan ◽  
Blaine Brower ◽  
Mary W. Dunn ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Serious Adverse Events ◽  
Free Survival ◽  
Castration Resistant ◽  
Radium 223 ◽  
Skeletal Event

Introduction Radium-223, abiraterone, and enzalutamide have each been shown to significantly improve survival as monotherapy in patients with metastatic castration-resistant prostate cancer. However, effects of combination radium-223 plus abiraterone or enzalutamide on survival and safety remain unclear. Patients and methods This single-center retrospective cohort study used electronic health record data of patients with metastatic castration-resistant prostate cancer and bone metastases who were treated with radium-223 between April 1, 2014 and February 19, 2019. Patients who received radium-223 monotherapy were compared to patients who received a combination of radium-223 plus either abiraterone or enzalutamide. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, time to symptomatic skeletal event, symptomatic skeletal event-free survival, and incidence of drug-related adverse events. Time-to-event analyses were estimated by log rank tests using Kaplan-Meier curves. Hazard ratios and 95% confidence intervals were derived from Cox proportional hazards models. Chi-square tests evaluated difference in serious adverse events between the two arms. Results A total of 60 patients met inclusion criteria (n = 41 in the monotherapy arm, n = 19 in the combination arm). Differences in median overall survival were not observed (12.7 vs. 12.8 months; HR 1.15, 95% CI 0.59–2.23; P = 0.68), but median progression-free survival was significantly longer in the combination arm (7.6 vs. 4.9 months; HR 1.94, 95% CI 1.11–3.40; P = 0.02). Significant differences were not observed in time to first SSE (P = 0.97), SSE-free survival (P = 0.16), or in the overall incidence of serious adverse events (P = 0.45). Conclusion Combination radium-223 plus abiraterone or enzalutamide did not improve overall survival, but prolonged progression-free survival without increasing the incidence of serious adverse events in metastatic castration-resistant prostate cancer patients with bone metastases. However, these results are limited by small numbers and patient selection inherent in retrospective analysis.

Interim and End-treatment 18F-Fluorocholine PET/CT and Bone Scan in Prostate Cancer Patients Treated with Radium 223 Dichloride

2021 ◽  
Author(s):  
Ana Maria Garcia Vicente ◽  
Mariano Amo-Salas ◽  
Javier Cassinello Espinosa ◽  
Roberto Gomez Diaz ◽  
Angel Soriano Castrejon
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Therapeutic Failure ◽  
Castration Resistant Prostate Cancer ◽  
Clinical Progression ◽  
Free Survival ◽  
Castration Resistant ◽  
Radium 223 ◽  
Pet Ct ◽  
Biochemical Progression

Abstract AimTo assess the predictive and prognostic aim of interim and end-treatment 18F-fluorocholine PET/CT (FCH-PET/CT) and 99mTc-methilen diphosphonate bone scintigraphy (BS) in patients with castration-resistant prostate cancer and bone metastases (CRPC-BM) treated with Radium 223 dichloride (223Ra). Methods: Prospective and multicentre ChoPET-Rad study including 82 patients with CRPC-BM. Baseline, after 3 (interim) and 6 doses (end-treatment) BS and FCH PET/CT were performed in patients who meet the study criteria. Clinical variables, imaging and clinical progression were obtained and their association with progression free survival (PFS), and overall survival (OS) was studied. Agreement between BS and FCH PET/CT response was assessed using Kappa (K) analysis.Results:Median of PFS and OS was 3 and 16 months, respectively. Agreement between interim BS and FCH PET/CT was weak (K: 0.28; p=0.004). No agreement was observed between end-treatment diagnostic studiesInterim and end-treatment FCH PET/CT were related to PFS (p=0.011 and p<0.001, respectively). Therapeutic failure and interim BS and FCH PET/CT showed association with OS (p<0.001, p=0.037 and p=0.008, respectively).Conclusions: Interim and end-treatment FCH PET/CT were good predictors of biochemical progression in patients treated with 223Ra. Therapeutic failure and progression in interim BS or FCH PET/CT were adverse factors for OS.

Prognostic impact of prior local therapy in castration-resistant prostate cancer

2021 ◽  
Author(s):  
Mikifumi Koura ◽  
Masaki Shiota ◽  
Shohei Ueda ◽  
Takashi Matsumoto ◽  
Satoshi Kobayashi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Castration Resistant ◽  
Line Therapy

Abstract Objective This study aimed to reveal the prognostic values of prior local therapy in first-line therapy using androgen receptor-axis targeting agents (abiraterone or enzalutamide) or docetaxel for castration-resistant prostate cancer (CRPC). Methods The study included 303 patients treated with first-line therapy for non-metastatic and metastatic CRPC. The association between prior local therapy and therapeutic outcome including progression-free survival and overall survival was investigated by univariate and multivariate analyses as well as propensity score-matched analysis. Results In univariate analysis, local prior therapy was associated with a lower risk of all-cause mortality (hazard ratio, 0.56, 95% confidence interval, 0.40–0.79; P = 0.0009). Overall survival, but not progression-free survival, was better among patients with prior local therapy compared with patients without prior local therapy even after multivariate analysis and propensity score-matched analysis. Conclusions This study robustly indicated that prior local treatment was prognostic for overall survival among patients with CRPC. This finding is useful to predict patient prognosis in CRPC.

Phase II trial of opaganib in patients with metastatic castration-resistant prostate cancer progressing on abiraterone or enzalutamide (NCT04207255).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS191-TPS191
Author(s):  
Omer Kucuk ◽  
Charles Smith ◽  
Terry Plasse ◽  
Besim Ogretmen ◽  
Shikhar Mehrotra ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Modulation ◽  
Immune Cell ◽  
Progression Free Survival ◽  
Competitive Inhibitor ◽  
Cell Trafficking ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Sphingosine 1 Phosphate

TPS191 Background: Opaganib (Yeliva, ABC294640) is a first-in-class, sphingosine kinase-2 (SK2) selective inhibitor, with anticancer, anti-inflammatory and anti-viral activities. SK2, a lipid kinase catalyzes formation of the lipid signaling molecule sphingosine 1-phosphate (S1P). S1P promotes cancer growth, and proliferation and pathological inflammation, including inflammatory cytokine production. Specifically, by inhibiting the SK2 enzyme, opaganib blocks the synthesis of S1P which regulates fundamental biological processes such as cell proliferation, migration, immune cell trafficking and angiogenesis, and are also involved in immune-modulation and suppression of innate immune responses from T cells. Opaganib is a sphingosine-competitive inhibitor of SK2 and also inhibits dihydroceramide desaturase. Opaganib has antitumor activity against human and murine prostate cancer cell lines, and in xenograft (LNCaP) and syngeneic (MycCAP, TRAMP-C1) murine tumor models. In addition to its target effect of reducing sphingosine-1-phosphate, opaganib reduces both MYC and AR proteins through its kinase-blocking and desaturase-inhibiting properties, respectively. Methods: The study is open to patients with mCRPC who have been treated with at least one newer androgen antagonist (abiraterone or enzalutamide) and no prior chemotherapy for castration-resistant disease. Patients who are failing either abiraterone or enzalutamide may enroll, with the addition of opaganib. The trial design includes brief safety lead-in cohort 1a (abiraterone + opaganib 250 mg Q 12hr, 3/3 enrolled) and 1b (enzalutamide + opaganib 250 mg Q 12hr, 3/3 enrolled). These cohorts have been completed without any DLTs. We are now enrolling cohort 2 (abiraterone + opaganib 500 mg Q 12hr, 0/27 enrolled) and cohort 3 (enzalutamide + opaganib 500 mg Q 12hr, 8/27 enrolled). A total of 60 patients will be enrolled and response will be evaluated after 4 cycles (28 days/cycle) using a composite metric based on PSA, bone scan and RECIST measurements per PCWG3 criteria. Safety and tolerability will be monitored, and dose modifications will be allowed. Primary endpoint is disease control (stable disease or better) after 4 cycles. Secondary endpoints include overall survival, radiographic progression-free survival and PSA progression-free survival. Correlative studies include assessment of quality of life (QOL), circulating MDSCs, immune cells and clones with amplified AR or MYC. Supported by NIH grant P01 CA203628. Clinical trial information: NCT04207255.

scholarly journals Re‐treatment with radium‐223: 2‐year follow‐up from an international, open‐label, phase 1/2 study in patients with castration‐resistant prostate cancer and bone metastases

The Prostate ◽  
2019 ◽  
Vol 79 (14) ◽  
pp. 1683-1691 ◽  
Author(s):  
Oliver Sartor ◽  
Daniel Heinrich ◽  
Neil Mariados ◽  
Maria José Méndez Vidal ◽  
Daniel Keizman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Phase 1 ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Castration Resistant ◽  
Radium 223 ◽  
Open Label Phase
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