Who is a bone-predominant patient to maximize clinical benefits of radium-223 dichloride?

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 47-47
Author(s):  
Kohei Hashimoto ◽  
Yasuhide Miyoshi ◽  
Tetsuya Shindo ◽  
Naotaka Nishiyama ◽  
Shintaro Miyamoto ◽  
...  
Keyword(s):  
De Novo ◽  
Treatment Time ◽  
Subsequent Treatment ◽  
Optimal Decision ◽  
Castration Resistant Prostate Cancer ◽  
Visceral Metastasis ◽  
Dynamic Changes ◽  
Diagnostic Uncertainty ◽  
Radium 223 ◽  
Clinical Benefits

47 Background: Radium-223 dichloride (Ra-223) is used for patients with castration-resistant prostate cancer (CRPC) and bone metastasis (BM). However, some patients often have disease progression of non-BM during Ra-223 and may enable to receive no more other life-prolonging therapies. Thus, diagnostic uncertainty in bone-predominant CRPC yet needs to be determined. To maximize clinical benefits of Ra-223, we clarified how to identify patients with bone-predominant metastatic CRPC. Methods: This was a multi-center retrospective study. The 136 CRPC patients who received Ra-223 between 2012 and 2019 were reviewed. Patients without visceral metastasis and lymph node metastasis of more than 3 cm received Ra-223, 55kBq/kg, every 4 weeks for up to 6 cycles, and were required to continue androgen deprivation therapy alone. All patients were divided into 3 groups by the types of dynamic changes of BM compared to BM at diagnosis: i) only known lesions; ii) new progressive lesions; iii) de novo BM at CRPC. Time from initiation of Ra-223 to failure of subsequent treatment (time to FST), radiographic progression-free survival (rPFS) and overall survival (OS) were evaluated. Results: The median age was 76 years. Of all, 68% received all 6 planned cycles of Ra-223. Overall, PSA responses were observed in 26 (19%). During follow-up of 12 months, the median time of FST, rPFS and OS were 8.3, 10.6 and 16.4 months, respectively. The type of dynamic changes of BM (HR 3.65, p=0.004) and PSA doubling time (PSADT) just before Ra-223 (HR 4.35, p=0.006) were significantly associated with time to FST. The dynamic changes of BM combined with PSADT highlighted an optimal decision of Ra-223. Patients with only known lesions of BM had longer time to FST, better rPFS and OS regardless of PSADT. The same was true for patients with de novo or new progressive lesions of BM and a long PSADT. In contrast, patients with new progressive lesions of BM and PSADT< 3 months were presumably more likely to have the risk of FST and progression of visceral metastasis. Conclusions: Our findings suggest that the risk assessment with the type of dynamic changes of BM and PSADT could determine an ideal patient for Ra-223.

Clinical outcomes of a Dutch prospective observational registry of metastatic castration resistant prostate cancer (mCRPC) patients treated with radium-223 (Ra-223).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 323-323
Author(s):  
Rebecca Louhanepessy ◽  
Sushil Badrising ◽  
Vincent van der Noort ◽  
Jules L. L. M. Coenen ◽  
Paul Hamberg ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Clinical Outcomes ◽  
Spinal Cord Compression ◽  
Survival Data ◽  
Cord Compression ◽  
Subsequent Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Bone Surgery ◽  
Radium 223 ◽  
Pathologic Fractures

323 Background: In 2012 the ALSYMPCA study established a 3.6 month Overall Survival (OS) benefit of mCRPC patients treated with Ra-223 over placebo. To date clinical outcomes of Ra-223 treatment in a non-study population have not been prospectively evaluated. Methods: The ROTOR registry aimed to include 300 patients in 20 Dutch hospitals prior to Ra-223 treatment at the physician’s discretion. Clinical parameters collected included: positioning of Ra-223, Adverse Events (AE’s; CTCAE v4.03), Skeletal Related Events (SRE) and survival data. SRE was defined as radiotherapy to a bone metastasis, a new pathological fracture, spinal cord compression and/or bone surgery. Progression-Free Survival (PFS) was defined as survival until radiological or clinical progression, subsequent treatment or death. Results: Between April 2014 and September 2017, 305 patients were included of whom 300 were evaluable. The mean age of patients was 72.6 (range 46.3-91.5) years, 255 (85%) had ≥ 6 bone metastases and 197 (65.5%) were pretreated with taxanes and/or abiraterone or enzalutamide (214 (71.3%)). Two-hundred and ninety (96.7%) patients were treated with Ra-223. Twenty-nine (9.7%), 104 (34.7%), 96 (32%) and 66 (22%) patients received Ra-223 as a first, second, third, ≥ fourth mCRPC treatment line, respectively. Patients received an average of 4.6 (SD 1.8) cycles of Ra-223, while 140 (46.7%) completed all six cycles. After a median follow-up of 13.2 months, PFS was 5.1 (CI 4.5-5.8) months and OS 15.2 (CI 12.8-17.6) months. Eighty-two (27.3%) patients were hospitalized during Ra-223 treatment (Serious AE). Grade ≥ 3 anemia, neutropenia and thrombocytopenia was found in 54 (18.0%), 8 (2.7%) and 11 (3.7%) patients, respectively. Other frequent AE’s (all grades) were nausea (90 (30%)), diarrhea (83 (27.7%)) and fatigue (178 (59.3%)). SREs were observed in 46 (15.3%) patients; 22 (7.3%) received radiotherapy, 6 (2%) developed pathologic fractures, 17 (5.6%) spinal cord compression and 1 (0.3%) received bone surgery during Ra-223 therapy. Conclusions: The non-study ROTOR population had characteristics, all grade AEs and OS comparable with the treatment arm of ALSYMPCA. Clinical trial information: NCT03223597.

scholarly journals Progress in the Treatment of Advanced Prostate Cancer

2014 ◽  
pp. 117-131 ◽  
Author(s):  
Cora N. Sternberg ◽  
Daniel P. Petrylak ◽  
Ravi A. Madan ◽  
Chris Parker
Keyword(s):  
Prostate Cancer ◽  
Large Scale ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Cross Resistance ◽  
Tumor Escape ◽  
Castration Resistant Prostate Cancer ◽  
Hormonal Manipulation ◽  
Radium 223 ◽  
Clinical Benefits

The androgen receptor (AR) is the most significant target for patients with metastatic castration-resistant prostate cancer (mCRPC). There is now irrefutable evidence that the AR axis is functional in most patients throughout the history of prostate cancer, is crucial from diagnosis to death, even in patients who have received hormonal manipulation, and represents a relevant therapeutic target in all phases of the disease. The potential mechanisms of tumor escape after castration are multifold, with each mechanism today representing a therapeutic opportunity. Phase III trials have been able to demonstrate improved overall survival (OS), improved quality of life, decreased skeletal-related events, and other important clinical benefits in young and elderly patients. After the initial positive results with docetaxel chemotherapy in improving OS, further research has resulted in five new treatments in the past few years. Immunotherapy with sipuleucel-T, cabazitaxel chemotherapy, the androgen biosynthesis inhibitor abiraterone acetate, the antiandrogen enzalutamide, and the radioisotope radium-223 have all been shown to improve OS in large-scale, well-conducted clinical trials. Proper understanding of mechanisms of resistance and of cross-resistance among these agents, sequencing, and combinations is now a priority.

scholarly journals Dynamic changes of bone metastasis predict bone‐predominant status to benefit from radium‐223 dichloride for patients with castration‐resistant prostate cancer

2020 ◽  
Vol 9 (22) ◽  
pp. 8579-8588
Author(s):  
Kohei Hashimoto ◽  
Yasuhide Miyoshi ◽  
Tetsuya Shindo ◽  
Masakazu Hori ◽  
Yasumasa Tsuboi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Castration Resistant Prostate Cancer ◽  
Dynamic Changes ◽  
Castration Resistant ◽  
Radium 223

scholarly journals Metasztatikus hormonérzékeny prosztatadaganat korszerű kezelése

2018 ◽  
Vol 159 (41) ◽  
pp. 1664-1671
Author(s):  
Zsófia Küronya ◽  
Krisztina Bíró ◽  
Lajos Géczi ◽  
Anikó Maráz
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
De Novo ◽  
Androgen Deprivation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
Sensitive Phase ◽  
Hormone Sensitive ◽  
To Receive

Abstract: The treatment of metastatic prostate cancer can be divided into two pathophysiological phases: hormone-sensitive and castration-resistant phases. Huggins’ observation in the year 1941, which was awarded with the Nobel Prize in 1966, has a key role in treatment during the hormone-sensitive phase, stating that if the testicles are removed, the size of the prostate cancer decreases. Inducing androgen deprivation, i.e., testosterone depletion is the basic treatment of metastatic prostate cancer that patients have to receive life-long. In the past eight years, five new agents have been approved besides docetaxel in the treatment of metastatic castration-resistant prostate cancer: sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, and radium-223. With the sequential application of these agents, significant improvement can be achieved in survival. Besides the latest developments, the hormone-sensitive phase has become the focus of attention, especially in the treatment of patients with de novo metastases and poor prognosis. Many studies have proven the outstanding efficacy of adding early docetaxel and abiraterone to androgen deprivation therapy. The authors give a detailed overview of clinical studies leading to a paradigm change in treatment during the hormone-sensitive phase, and call attention to the difficulties encountered in Hungarian practice. Orv Hetil. 2018; 159(41): 1664–1671.

Treatment patterns for metastatic hormone-sensitive prostate cancer (mHSPC) progressing after up-front docetaxel in combination with androgen deprivation therapy (D-ADT).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 305-305
Author(s):  
Pedro C. Barata ◽  
Hamid Emamekhoo ◽  
Prateek Mendiratta ◽  
Dharmesh Gopalakrishnan ◽  
Vadim S. Koshkin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Response ◽  
Cleveland Clinic ◽  
Final Analysis ◽  
High Volume ◽  
Median Number ◽  
Subsequent Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Radium 223 ◽  
Visceral Disease

305 Background: D-ADT increases overall survival (OS) in men with mHSPC. All patients (pts) however progress and develop castration-resistant prostate cancer (CRPC). Little is known about response to subsequent therapy and outcomes in this setting. Methods: Retrospective analysis of consecutive mHSPC pts treated with ≥3 cycles of D-ADT at Cleveland Clinic and University of Wisconsin-Madison. We aimed to describe baseline, progression characteristics, treatment choices, sequence and outcome of subsequent therapy. Results: A total of 146 mHSPC pts were treated with D-ADT (6% 1-2 cycles; 94% ≥3 cycles). Final analysis included 136 pts, median age 65 (range 35-86), 65% GS≥8, 79% high-volume disease. Median number of D cycles was 6 (1-6). PSA declined to “0” at 12 and 24 months in 32% and 25% of pts, respectively. Median time to CRPC (biochemical, clinical or radiographic) was 19.6 months (95% CI, 16.6-22.6). 57 pts (42%) received ≥1 subsequent treatment after CRPC [46 hormonal therapy (HT) (21 abiraterone acetate, 19 enzalutamide, 6 ASN-001); 4 Sipuleucel-T; 4 radium-223, 5 chemotherapy (2 carboplatin-based, 2 cabazitaxel, 1 D); 3 temsirolimus/bevacizumab]. Treatment response was independent from time to CRPC (≥12 months, p = 0.264). Pts receiving HT as the first subsequent treatment had a median rPFS of 13.3 months (95% CI, 10.1-16.5) compared with 3.1 months (95% CI, 0-15.8) for non-HT (p = 0.332). Treatment choice was independent of GS (p = 0.513), visceral disease (p = 0.374) and time to CRPC (p = 0.500). Most CRPC pts treated with ≥2 lines of therapy received one HT (n = 21) followed by a different HT (43%), chemo (38%), radium-223 (14%) or olaparib (10%). 57% of pts were alive at 2 years. Longer OS correlated with time to CRPC (p = 0.010) and first subsequent treatment with HT (p = 0.009) but not with visceral disease (p = 0.258), GS (p = 0.599) or sequence of therapies received (HT/HT vs HT/non-HT, p = 0.836). Conclusions: Prior D-ADT did not preclude subsequent treatment response in CRPC pts, independent of time to CRPC. The choice of first-line treatment for CRPC may impact survival in favor of those who start HT.

Prognostic factors that affect survival outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 225-225
Author(s):  
Esmail Mutahar Al-Ezzi ◽  
Husam Alqaisi ◽  
Sarah Picardo ◽  
Marco Iafolla ◽  
Srikala S. Sridhar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bone Metastases ◽  
Cox Regression ◽  
Subsequent Treatment ◽  
Survival Outcomes ◽  
Castration Resistant Prostate Cancer ◽  
Median Baseline ◽  
Disease Characteristics ◽  
Radium 223 ◽  
Baseline Psa

225 Background: Radium-223 (Ra-223) improved overall survival (OS) in men with mCRPC with predominantly bone metastases. We analyzed their survival outcomes to identify factors associated with prognosis for men treated with Ra-223. Methods: This was a retrospective study of men with mCRPC at Princess Margaret Cancer Centre treated with Ra-223. Demographics, disease characteristics, number of bone metastasis [ < 6, 6-20, > 20], laboratory results, number of Ra-223 doses, systemic treatment lines after radium-223, use of bone protecting agents (BPA) and survival outcomes were collected. OS and progression-free survival (PFS) were estimated by Kaplan-Meier (log-rank) analysis. Uni- (UVA) and multi-variate (MVA) analysis (Cox-regression) were used to evaluate patient and disease characteristics, number of Ra-223 doses and overall survival. Results: 114 men received Ra-223 between May 2015 and May 2018 with median age 75 years (range 53-93). Median radium doses was 5 (68 [59.6%] received > 4 doses, 46 [40.4%] received ≤4 doses). Median baseline ALP 113.5 U/L (31-1121), median baseline Hb 118 g/L (69-153), median baseline PSA 70.2 ug/L (0.15-5275), median LDH 242 UL (82-1426). 58% had 6-20 bone metastases and 28% had > 20 bone metastases. The median OS and PFS for men who received ≤4 doses vs > 4 doses was 4.56 vs 19.8 months (HR = 8.4; 95%CI: 4.861-14.62; p≤ 0.0001) and 2.9 vs 7.45 months (HR = 4.6; 95%CI: 2.837 to 7.537; p≤ 0.0001) respectively. The baseline median ALP was (154 vs 98; p = 0.03) for men who received ≤4 doses vs > 4 doses Ra-223. On UVA, ECOG 0-1 (HR = 0.33; p = 0.0003), baseline PSA < 70 ug/L (HR = 0.51; p = 0.0023), LDH < 250 U/L (HR 0.55; p = 0.0082), Hb > 120 g/L(HR 0.46; p = 0.0004), ALP < 150 U/l(HR 0.38; p ≤ 0.0001) and receipt of subsequent treatment after Ra-223 (HR = 0.33; p < 0.0001) were associated with improved OS. On MVA, receipt of subsequent treatment, administration > 4 cycles of Ra-223 and baseline ALP < 150 U/L were associated with improved OS. Conclusions: Men who receive > 4 cycles of Ra-223 have significantly better OS than those who receive ≤4 doses. Baseline ALP was independently associated with better OS and could be used to identify patients most likely to benefit from Ra-223.

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.

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