scholarly journals Pain response in a population-based study of radium-223 (Ra223) for metastatic castration-resistant prostate cancer

2018 ◽  
Vol 13 (10) ◽  
pp. E311-6
Author(s):  
Sunil Parimi ◽  
Suraya Bondy ◽  
Erica Tsang ◽  
Michael Ross McKenzie ◽  
Francois Bachand ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
External Beam Radiotherapy ◽  
Brief Pain Inventory ◽  
Population Based ◽  
Response Threshold ◽  
Injection Pain ◽  
Pain Response ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223

Introduction: Clinical trials have shown that radium-223 (Ra223) can prolong survival and improve quality of life in patients with metastatic castration-resistant prostate cancer (mCRPC). The objectives of this study were to evaluate pain responses with Ra223 at a population-based level and to determine if there is an association between pain response and alkaline phosphatase (ALP) response. Methods: All patients from the Vancouver and Kelowna Cancer Centers (CC) in British Columbia who were treated with Ra223 between June 2015 and December 2016 were identified. Patients completed the Brief Pain Inventory (BPI) just prior to each Ra223 injection. Pain response was defined as a two or more point improvement in worst pain relative to baseline, without an increase in pain medication level. ALP was determined at each visit, with a response threshold defined as a 30% decrease from baseline, consistent with the definition of response used in the ALSYMPCA trial. Results: A total of 65 patients in Vancouver and Kelowna CC received Ra223 during the study period and 56 patients had at least one BPI record, of which 44 (79%) patients were assessable for change in worst pain. Of the assessable patients, 23 (52%, 95% confidence interval [CI] 38–67) had a pain response, although the use of concurrent external beam radiotherapy was a confounder in four cases. Of the 44 patients assessable for change in worst pain, 59% had ALP responses greater than 30%. An ALP response was seen in 56% of pain-responders vs. 43% of non-pain-responders. There was no association between pain response and ALP response (Phi =-0.05; p=0.77). Conclusions: Ra223 administration was associated with a meaningful pain response rate in this cohort. There was no correlation between pain response and ALP response.

A meta-analysis on individual data of bone-targeting radio-isotopes in men with bone metastases from castration-resistant prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 352-352
Author(s):  
Safae Aarab Terrisse ◽  
Chris C. Parker ◽  
Karamouza Eleni ◽  
A. Oliver Sartor ◽  
Nicholas James ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Meta Analysis ◽  
External Beam Radiotherapy ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
Significant Difference ◽  
Radio Isotopes

352 Background: Among bone-targeted radio-isotopes (RI), Radium-223 (an α-emitter) is the only one with clearly demonstrated overall survival (OS) benefit in men with castration-resistant prostate cancer (CRPC). The aim of this meta-analysis is to estimate the OS impact of RI in men with CRPC. Methods: An individual patient data meta-analysis was carried out from randomized trials with inclusion period 1993-2013. Eligible trials included more than 50 patients, mandated bone metastases from CRPC and randomly evaluated RI. Endpoints were OS (primary), symptomatic skeletal events (SSE) and toxicity. A fixed-effect model was used. The log-rank test stratified by trial was used to estimate individual and overall hazard ratios (HR). Subset analyses were performed by the type of radiation (α vs. β emission) and by trial comparison: RI + Chemotherapy (CT) vs. CT, RI+ External beam radiotherapy (EBRT) vs. EBRT, RI vs. EBRT. Results: From 9 identified trials, data from 6 trials comprising 2081 patients (min: 64, max: 921) were collected with 2 trials representing 80% of data. The data from 3 trials (n = 341) were not available. The overall effect on OS favoured RI with HR = 0.86 [0.77-0.95] but high heterogeneity between trials (p < 0.001, I2= 79.6%). The overall effect of α- emitters on OS (HR = 0.70 [0.58; 0.83], 2 trials, n = 985) significantly differed from that of β-emitters (HR = 0.96 [0.84; 1.10], n = 4 trials, n = 1096) (interaction p = 0.0041). The overall effect on SSE favoured RI with HR = 0.81 [0.69-0.93] (4 trials, n = 1806) with marked between trial heterogeneity (p = 0.08, I² = 55.3%) and a significant difference (p = 0.02) by the type of RI (α-emitters: HR = 0.65 [0.52-0.82]-2 trials, β-emitters: HR = 0.93 [0.77-1.13]-2 trials). Conclusions: In men with metastatic CRPC a significant improvement of OS and SSE was obtained with bone targeted α-emitter radio isotopes, but not with β-emitter. However, some between trial heterogeneity of effects on OS need further investigations.

scholarly journals Bone pain palliation outcomes and possibility of Radium-223 re-treatment in mCRPC

2020 ◽  
Vol 92 (3) ◽  
Author(s):  
Viviana Frantellizzi ◽  
Julia Lazri ◽  
Mariano Pontico ◽  
Arianna Pani ◽  
Giuseppe De Vincentis
Keyword(s):  
Prostate Cancer ◽  
Bone Scan ◽  
Bone Pain ◽  
Brief Pain Inventory ◽  
Pain Palliation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Bone Pain Palliation ◽  
Radium 223 ◽  
Pain Symptoms

Objective. Bone secondary localizations from metastatic castration-resistant prostate cancer are associated with an increase in mortality and a reduction in the patient’s quality of life. Radium-223 is a targeted alpha-therapy approved for the treatment of mCRPC (metastatic castration resistant prostate cancer) patients with symptomatic bone metastases. To our knowledge, no previous study has been performed assessing the bone pain palliation outcomes following Radium-223 therapy. Materials and Methods. A mCRPC patient with symptomatic bone localizations and relevant bone pain symptoms has been subjected to Radium-223 treatment. Pain was assessed over time from the first administration of Radium-223 to follow-up. Results. After Radium-223 treatment, patient showed a significant BPI (Brief Pain Inventory) decline from 7 to 4 and a concomitant partial regression of multiple bone hot spots in the bone scan exam. Three months after the last infusion of Radium-223, further BPI decline (from 4 to 2) with bone scan depicting stable disease was observed. However, after 6 months from Radium-223 treatment end, BPI increased from 2 to 10. Conclusions. Taking into account the effectiveness on bone pain relief and the low toxicity profile showed by Radium-223 treatment, we encourage further analysis on large cohort to investigate the clinical outcome after Radium-223 treatment, in terms of bone pain palliation, together with the possibility of Radium-223 re-treatment in selected patients..

scholarly journals Early alkaline phosphatase dynamics as biomarker of survival in metastatic castration-resistant prostate cancer patients treated with radium-223

2021 ◽  
Author(s):  
Maarten J. van der Doelen ◽  
Agnes Stockhaus ◽  
Yuanjun Ma ◽  
Niven Mehra ◽  
Jeffrey Yachnin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Alkaline Phosphatase ◽  
Confidence Interval ◽  
Surrogate Marker ◽  
Response Monitoring ◽  
Castration Resistant Prostate Cancer ◽  
Related Event ◽  
Castration Resistant ◽  
Radium 223 ◽  
Skeletal Related Event

Abstract Purpose Radium-223 is a life-prolonging therapy for castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. However, validated biomarkers for response monitoring are lacking. The study aim was to investigate whether early alkaline phosphatase (ALP) dynamics after the first radium-223 injection can act as surrogate marker for overall survival (OS). Methods This retrospective multicenter study included consecutive CRPC patients treated with radium-223. Patients were divided into four subgroups based on baseline ALP level (normal/elevated) and early ALP response, defined as ≥10% ALP decrease after the first radium-223 injection. Primary endpoint was OS among the subgroups. Secondary endpoints included time to first skeletal-related event, time to ALP progression, and treatment completion rate. Results A total of 180 patients were included for analysis. Median OS was 13.5 months (95% confidence interval 11.5–15.5). Patients with elevated baseline ALP without ALP response after the first injection had significantly worse OS when compared to all other patients (median OS 7.9 months versus 15.7 months, hazard ratio 2.56, 95% confidence interval 1.73–3.80, P < 0.001). Multivariate analysis demonstrated that elevated baseline ALP without ALP response after the first injection, the number of prior systemic therapies, baseline LDH level, and baseline ECOG performance status were prognostic factors of OS. Patients with elevated baseline ALP without ALP response after the first injection had significantly shorter times to ALP progression and first skeletal-related event, and more frequently discontinued radium-223 therapy when compared to other patients. Conclusion Early treatment–induced changes in ALP after one radium-223 injection were associated with OS in metastatic CRPC patients.

Decreased fracture rate by mandating bone protecting agents in the EORTC 1333/PEACEIII trial combining Ra223 with enzalutamide versus enzalutamide alone: An updated safety analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5002-5002
Author(s):  
Silke Gillessen ◽  
Ananya Choudhury ◽  
Alejo Rodriguez-Vida ◽  
Franco Nole ◽  
Enrique Gallardo Diaz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Safety Analysis ◽  
Phase Iii ◽  
Fracture Rate ◽  
Castration Resistant Prostate Cancer ◽  
Continuous Administration ◽  
Castration Resistant ◽  
Radium 223 ◽  
Safety Population

5002 Background: The randomized phase III EORTC-1333-GUCG (NCT02194842) trial compares enzalutamide vs. a combination of Radium 223 and enzalutamide in asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC) patients. The premature unblinding of ERA223 (NCT02043678) in Nov 2017 due to a significant increase in the rate of fractures in the combination of abiraterone and Ra223 arm led to the implementation of the mandatory use of bone protecting agents (BPA) in the EORTC-1333-GUCG trial. Skeletal fractures, pathological or not, are a frequent and underestimated adverse event of systemic treatment of advanced prostate cancer. Whether this mandated use of BPA (zoledronic acid or denosumab) would mitigate the risk of fractures in this patient population was unclear. An early safety analysis (Tombal, ASCO, 2019) suggested that the risk of fractures was well controlled in both arms when patients receive BPA. We present here an updated analysis of fracture incidence with longer follow-up. Methods: As of 28/01/2021, a total of 253 patients (134 after making BPA mandatory) were randomized between enzalutamide/Ra223 and enzalutamide. The fracture rate was estimated with the cumulative incidence method in the safety population of 237 (122 after making BPA mandatory) treated patients. Death in absence of fracture was analyzed as competing risk and censoring was applied at last follow-up. Results: Overall, 69.5% of enzalutamide/Ra223 patients (95.2% after making BPA mandatory) and 73.1% of enzalutamide patients (95% after making BPA mandatory) received BPA on treatment: 13.6% in the enzalutamide/Ra223 arm and 21.8% in the enzalutamide arm did not use BPA at registration, but started during protocol treatment and 55.9% and 51.3% respectively, received BPA since entry. At 36.7 months median follow-up in patients without BPA and 23.1 months median follow-up in patients receiving BPA, a total of 39 patients reported a fracture. Among them, 30 patients (20 in enzalutamide/Ra223 arm) did not receive BPA and 9 (4 in the enzalutamide/Ra223 arm) received BPA (see table). Conclusions: The updated safety analysis confirms the early fracture rate results. In the absence of BPA, the risk of fracture is increased when RA223 is added to enzalutamide. Strikingly, in both arms, the risk remains almost abolished by a preventive continuous administration of BPA, thus stressing the importance of complying to international recommendations in terms of giving BPA to mCRPC patients. This study is sponsored by EORTC and supported by Bayer and Astellas. Clinical trial information: NCT02194842. [Table: see text]

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