Risk factors of skeletal-related events in patients with bone metastatic castration-resistant prostate cancer undergoing treatment with zoledronate

2021 ◽  
Author(s):  
Hirotaka Miyashita ◽  
Christina Cruz ◽  
Vaibhav Patel
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Skeletal Related Events

scholarly journals Impact of Extraskeletal Metastases on Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer with Bone Metastases

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2034
Author(s):  
Soraia Lobo-Martins ◽  
Arlindo R. Ferreira ◽  
André Mansinho ◽  
Sandra Casimiro ◽  
Kim Leitzel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Unmet Need ◽  
Bone Alkaline Phosphatase ◽  
Multicenter Clinical Trial ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Therapeutic Landscape ◽  
Skeletal Related Events ◽  
The Impact

The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has substantially evolved over the last decade. Nonetheless, a better understanding of bone-targeted agents (BTAs) action in mCRPC remains an unmet need. Theuse of BTAs aims to reduce the incidence of skeletal-related events (SREs) in patients with mCRPC. Less frequent BTA schedules are currently being studied to minimize adverse events. In this study, the impact of metastatic compartment (bone and extraskeletal metastases (BESM) vs. bone-only metastases (BOM)) on bone biomarker kinetics, time to first on-study SRE, and symptomatic skeletal events (SSEs) is evaluated. This is a retrospective analysis of the prospective, randomized, multicenter clinical trial of denosumab vs. zoledronic acid in patients with mCRPC and bone metastases. A total of 1901 patients were included, 1559 (82.0%) with BOM and 342 with BESM (18.0%). Bone metastases burden was balanced between groups. Baseline levels and normalization rates of corrected urinary N-terminal telopeptide and bone alkaline phosphatase did not differ between groups. However, BESM patients had a higher risk of SREs (adjusted HR 1.21; 95% CI 1.01–1.46; p = 0.043) and SSEs (adjusted HR 1.30; 95% CI 1.06–1.61; p = 0.014). This difference was more pronounced in the first 12 months of BTA treatment.In mCRPC, strategies of BTA schedule de-escalation may take into account presence of extraskeletal metastases.

scholarly journals Management of Anticoagulation in Patients With Prostate Cancer Receiving Enzalutamide

2017 ◽  
Vol 13 (11) ◽  
pp. 720-727 ◽  
Author(s):  
Joseph J. Shatzel ◽  
Molly M. Daughety ◽  
Sven R. Olson ◽  
Tomasz M. Beer ◽  
Thomas G. DeLoughery
Keyword(s):  
Prostate Cancer ◽  
Heart Valves ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Receptor Antagonist ◽  
Body Of Knowledge ◽  
Castration Resistant ◽  
Concurrent Use ◽  
Management Paradigms ◽  
Skeletal Related Events

Enzalutamide, a novel, oral androgen receptor antagonist used for the treatment of metastatic, castration-resistant prostate cancer, has been shown to improve overall and progression-free survival, prolong time to initiation of chemotherapy, reduce skeletal-related events, and carry a favorable adverse effect profile. Metastatic prostate cancer is a disease of older men, a population with an increased incidence of medical comorbidities warranting anticoagulation. Prostate cancer itself, along with some of its therapies, is also prothrombotic. Enzalutamide interacts with several anticoagulants through various mechanisms, making their concurrent use clinically challenging. As such, complex decisions about anticoagulation in these patients are frequently encountered by treating physicians. In this review, we describe the potential interactions between enzalutamide and various anticoagulants, and suggest management paradigms based on the current body of knowledge for patients with atrial fibrillation, venous thromboembolism, and mechanical heart valves.

scholarly journals Incidence of Skeletal-Related Events in Patients with Castration-Resistant Prostate Cancer: An Observational Retrospective Cohort Study in the US

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Alison Tse Kawai ◽  
David Martinez ◽  
Catherine W. Saltus ◽  
Zdravko P. Vassilev ◽  
Montse Soriano-Gabarró ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Incidence Rate ◽  
Incidence Rates ◽  
Negative Consequences ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Castration Resistant ◽  
The Us ◽  
History Of ◽  
Skeletal Related Events

Background and Objective. Skeletal-related events (SREs) are common in men with bone metastases and have negative consequences for patients with castration-resistant prostate cancer (CRPC), including pain, reduced quality of life, and increased mortality. We estimated incidence rates of first SREs in a cohort of men with CRPC in the Surveillance, Epidemiology, and End Results-Medicare database. Methods. We included men aged ≥ 65 years with a prostate cancer diagnosis in 2000-2011 if they had no prior malignancy (other than nonmelanoma skin cancer) and had surgical or medical castration with subsequent second-line systemic therapy, which was used to infer castration resistance. The first occurrence of an SRE (fracture, bone surgery, radiation therapy, or spinal cord compression) in Medicare claims was identified. Incidence rates of SREs were estimated in all eligible person-time and, in secondary analyses, stratified by any use of bone-targeted agents (BTAs) and history of SRE. Results. Of 2,234 men with CRPC (84% white, mean age = 76.6 years), 896 (40%) had an SRE during follow-up, with 74% occurring within a year after cohort entry. Overall, the incidence rate of SREs was 3.78 (95% CI, 3.53-4.03) per 100 person-months. The incidence rate of SREs before any BTA use was 4.16 (95% CI, 3.71-4.65) per 100 person-months, and after any BTA use was 3.60 (95% CI, 3.32-3.91) per 100 person-months. The incidence rate in patients with no history of SRE was 3.33 (95% CI 3.01-3.68) per 100 person-months, and in patients who had such a history, it was 4.20 (95% CI 3.84-4.58) per 100 person-months. Conclusions. In this large cohort of elderly men with CRPC in the US, SREs were common. A decrease in incidence of SREs after starting BTA is suggested, but the magnitude of the effect may be confounded by indication and other factors such as age and prior SRE.

Calcium metabolism in patients with castration-resistant prostate cancer: Development of a quantitative urinary assay for extent of bone metastasis.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 130-130
Author(s):  
Ashok P. Pai ◽  
Darren Hillegonds ◽  
Primo Lara ◽  
Chong-xian Pan ◽  
David Shelton
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Bone Turnover ◽  
Disease Progression ◽  
Calcium Metabolism ◽  
Castration Resistant Prostate Cancer ◽  
Disease Extent ◽  
Castration Resistant ◽  
Skeletal Related Events ◽  
Bony Metastases

130 Background: In patients with metastatic castration-resistant prostate cancer (CRPC), the degree of perturbation from normal bone turnover provides a strong indication of risk for disease progression, skeletal complications and death. Biomarkers of bone cell function and bone collagen degradation provide an integrated index of the underlying disease for patients with bony metastases, but available bone markers are not precise or accurate. In this study, patients with CRPC with bony metastases will consume a single oral calcium-41 dose and the pharmacokinetics of this will be measured over an 18 month period. Participants will also be assessed clinically for time to progression, skeletal related events and death. Methods: Patients with metastatic castration-resistant prostate cancer and bony metastatses, as diagnosed via bone scintigraphy, who were on bisphosphonates were enrolled into the study. 12 consenting research subjects consumed a single 1.2 microgram 41Ca tracer dose and provided 30-250mL urine specimens (single voids) after dose on day 1 (6h after dosing), days 7, 14, 28, 42, 60, and monthly thereafter. Isotope ratios were measured via accelerator mass spectrometry. Results: Urinary 41Ca/Ca was significantly and inversely associated with increased skeletal tumor burdens suggesting that development of an isotopic urine test for bone metastasis extent is feasible, providing a non-invasive and quantitative measure of disease extent. A calculation of the area under the curve of the measurements between day zero and 14 were inversely correlated with disease extent at baseline. Clinical deterioration with worsening bony disease was associated with a significant decrease in the urinary 41Ca/Ca value. We are currently assessing correlations between bone turnover and outcomes such as therapy effectiveness, disease progression, skeletal related events and death. Conclusions: This work is the first direct measurement of long-term calcium metabolism in advanced prostate cancer, providing a basic scientific complement to cellular and collagen-based measures of bone formation and resorption rates as well as a correlation to clinically relevant outcomes.

Identification of a predictive factor of metastatic castration-resistant prostate cancer patients’ response to alternative antiandrogen therapy with flutamide.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 321-321
Author(s):  
Masato Yasui ◽  
Shuko Yoneyama ◽  
Koichi Uemura ◽  
Takashi Kawahara ◽  
Yusuke Hattori ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Hormone Therapy ◽  
Predictive Factors ◽  
Hormonal Therapy ◽  
Bone Scan ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
N Stage

321 Background: Recently, new androgen pathway inhibitors, abiraterone and enzalutamide, are demonstrated to improve overall survival for metastatic castration-resistant prostate cancer (mCRPC). In Japan, alternative antiandrogen (AA) as second-line hormonal therapy for mCRPC that relapses after initial hormone therapy have been commonly used before new androgen pathway inhibitors. In this study, we attempted to identify the predictive factors for efficacy of AA as second-line hormone therapy. Methods: We identified consecutive 65 mCRPC patients treated with AA as second-line hormonal therapy. All patients were treated with maximum androgen blockade (MAB) initially and evaluated antiandrogen withdrawal syndrome after relapse. We analyzed the correlations between progression-free survival (PFS) of AA and clinicopathological characteristics, including patients’ age, initial PSA levels, PSA levels at flutamide induction, Gleason scores, T stage, N stage, extent of disease (EOD) classifications on bone scan, and the previous duration of prostate cancer sensitivity to MAB. Results: The median duration of prostate cancer sensitivity to MAB was 11.3 months (range: 1.5-53.0 months). In multivariate analysis, four significant risk factors for poor PFS were identified; initial PSA levels ( > 263 ng/mL vs ≤ 263; HR 0.53, p = 0.038), N stage (1 vs 0; HR 3.00, p = 0.001), EOD classifications (3-4 vs 1-2; HR 2.50, p = 0.007), and the previous duration of prostate cancer sensitivity to MAB ( < 12 months vs ≥ 12; HR 2.16, p = 0.026). We stratified the patients into two cohorts with low risk (0-2 risk factor present) and high risk (3-4 risk factors present). We found a significant difference in PFS among risk groups (median PFS 7.3 months vs 1.5, p < 0.000). Conclusions: Initial PSA, N stage, EOD classifications on bone scan, and the previous duration of prostate cancer sensitivity to MAB were the significant predictive factors for efficacy of AA as second-line hormone therapy in patients with mCRPC. These findings might support that decision-making of when to start the new AR pathway inhibitors.

Incidence of skeletal-related events in men with castration-resistant prostate cancer.

2018 ◽  
Vol 36 (34_suppl) ◽  
pp. 188-188
Author(s):  
Alison Tse Kawai ◽  
David Martinez ◽  
Catherine W. Saltus ◽  
Zdravko Vassilev ◽  
Montse Soriano-Gabarro ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Real World ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Cohort Entry ◽  
Risk Of Death ◽  
Castration Resistant ◽  
Increased Risk ◽  
Before And After ◽  
Skeletal Related Events

188 Background: Skeletal-related events (SREs) are common in men with bone metastases and have negative consequences for patients with castration-resistant prostate cancer (CRPC), including pain, reduced quality of life, and increased risk of death. Published data on background rates of SREs in men with CPRC in real-world practice are sparse. Methods: We included men aged ≥ 65 years in the SEER-Medicare database with a prostate cancer diagnosis in 2000-2011 if they had no prior malignancy, had surgical or medical castration, and met protocol-defined criteria for castration resistance. Castration resistance was inferred from subsequent treatment with any of these systemic therapies: abiraterone, cabazitaxel, docetaxel, enzalutamide, mitoxantrone, or sipuleucel-T. The first occurrence of an SRE was identified in Medicare claims using diagnosis or procedure codes for fracture, bone surgery, radiation therapy, or spinal cord compression. We estimated incidence rates (IRs) of SREs in all eligible person-time and stratified by person-time before and after any use of the following bone-targeted agents (BTAs): alendronate, denosumab, ibandronate, pamidronate, risedronate, or zoledronic acid. Results: Of 2,234 men with CRPC (84% white, mean age 76.6 years), 896 (40%) had an SRE during follow-up, with 74% occurring within a year after cohort entry. Overall, the IR of SREs was 3.78 (95% CI, 3.53-4.03) per 100 person-months. The IR of SREs before any BTA use was 4.16 (95% CI, 3.71-4.65) per 100 person-months, and after any use was 3.60 (95% CI, 3.32-3.91) per 100 person-months. Conclusions: In this large cohort of elderly men with CRPC in a real-world setting in the U.S., SREs were common, with most occurring within a year after cohort entry. Although a direct causal interpretation of the difference in rates before and after BTA use is not possible (since confounding by indication and other factors cannot be excluded), further analysis may address at least some potential confounders.

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