scholarly journals Radiotherapy of Oligoprogressive Lesions in Castration-Resistant Prostate Cancer: Impact on Second-Generation Hormone Therapy

2021 ◽  
Vol 12 (05) ◽  
pp. 302-310
Author(s):  
Kanta Ka ◽  
Papa Macoumba Gaye ◽  
Awa Sadikh Badiane ◽  
Ibrahima Thiam ◽  
Mouhamadou Bachir Ba ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hormone Therapy ◽  
Second Generation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Treatment of nonmetastatic castration-resistant prostate cancer: focus on second-generation androgen receptor inhibitors

2021 ◽  
Author(s):  
Fred Saad ◽  
Martin Bögemann ◽  
Kazuhiro Suzuki ◽  
Neal Shore
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Second Generation ◽  
Imaging Techniques ◽  
Specific Antigen ◽  
Conventional Imaging ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Therapeutic Decisions ◽  
Consensus Statements

Abstract Background Nonmetastatic castration-resistant prostate cancer (nmCRPC) is defined as a rising prostate-specific antigen concentration, despite castrate levels of testosterone with ongoing androgen-deprivation therapy or orchiectomy, and no detectable metastases by conventional imaging. Patients with nmCRPC progress to metastatic disease and are at risk of developing cancer-related symptoms and morbidity, eventually dying of their disease. While patients with nmCRPC are generally asymptomatic from their disease, they are often older and have chronic comorbidities that require long-term concomitant medication. Therefore, careful consideration of the benefit–risk profile of potential treatments is required. Methods In this review, we will discuss the rationale for early treatment of patients with nmCRPC to delay metastatic progression and prolong survival, as well as the factors influencing this treatment decision. We will focus on oral pharmacotherapy with the second-generation androgen receptor inhibitors, apalutamide, enzalutamide, and darolutamide, and the importance of balancing the clinical benefit they offer with potential adverse events and the consequential impact on quality of life, physical capacity, and cognitive function. Results and conclusions While the definition of nmCRPC is well established, the advent of next-generation imaging techniques capable of detecting hitherto undetectable oligometastatic disease in patients with nmCRPC has fostered debate on the criteria that inform the management of these patients. However, despite these developments, published consensus statements have maintained that the absence of metastases on conventional imaging suffices to guide such therapeutic decisions. In addition, the prolonged metastasis-free survival and recently reported positive overall survival outcomes of the three second-generation androgen receptor inhibitors have provided further evidence for the early use of these agents in patients with nmCRPC in order to delay metastases and prolong survival. Here, we discuss the benefit–risk profiles of apalutamide, enzalutamide, and darolutamide based on the data available from their pivotal clinical trials in patients with nmCRPC.

Abstract C16: Targeting AR in castration-resistant prostate cancer: Development of ARN-509 and second-generation antiandrogen resistance models

2012 ◽  
Vol 72 (4 Supplement) ◽  
pp. C16-C16
Author(s):  
James D. Joseph ◽  
Anna Aparicio ◽  
Josh Kaufman ◽  
Jackie Julien ◽  
Celine Bonnefous ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Second Generation ◽  
Cancer Development ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Prostate Cancer Development

Evaluating the effect of therapy duration on survival in patients with metastatic castration-resistant prostate cancer receiving radium-223.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e593-e593
Author(s):  
Noelle L. Williams ◽  
Kamila Nowak-Choi ◽  
Jenna Skowronski ◽  
Tu Dan ◽  
Harriet Belding Eldredge ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Second Generation ◽  
Cox Regression ◽  
Rank Test ◽  
Maximal Effect ◽  
Castration Resistant Prostate Cancer ◽  
Cox Regression Analysis ◽  
Castration Resistant ◽  
Full Treatment ◽  
Radium 223

e593 Background: The use of radium-223 in patients with metastatic castration-resistant prostate cancer (mCRPC) improves overall survival (OS) and quality of life. Combination of radium-223 with second-generation anti-androgens has further improved OS; however, the optimal length of radium-223 treatment for maximal effect remains unknown. Methods: We reviewed 35 consecutive patients with mCRPC who received radium-223 from December 2012 to August 2015 at Thomas Jefferson University. Patients were divided into two groups: those who received full treatment of 6 injections (n = 18) versus those who received less than 6 injections (n = 17). Kaplan-Meier analysis of OS were tested for difference by treatment group using Log Rank test. Univariable association with survival outcomes was calculated with univariable Cox regression and Log Rank tests. Results: Mean age was 73 ± 10 years and Karnofsky performance status (KPS) ranged from 50-90 (median, 80). Median follow-up was 13.9 months. Eighteen patients were receiving concurrent second generation anti-androgens at the start of treatment. Median OS was 12 months for patients who received 6 injections and 6.48 months for patients who received less than 6 injections (p = 0.0045). The results of univariate Cox regression analysis revealed full treatment was associated with increased OS (p = 0.0013). On multivariate analysis accounting for KPS, full treatment was significantly associated with improved OS (p = 0.0028). Conclusions: In this retrospective, single-institution analysis, we demonstrated that full course completion of radium-223 was associated with improved OS in patients with mCRPC. These patients should be optimally supported during treatment to allow for therapy completion.

scholarly journals Treatment-Emergent Co-Morbidities and Survival in Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Abiraterone or Enzalutamide

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi-Ting Lin ◽  
Yen-Chun Huang ◽  
Chih-Kuan Liu ◽  
Tian-Shyug Lee ◽  
Mingchih Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Hormone Therapy ◽  
Cox Regression ◽  
Castration Resistant Prostate Cancer ◽  
Drug Induced ◽  
Cox Regression Analysis ◽  
Castration Resistant ◽  
Significant Difference ◽  
Taiwan National Health Insurance

Secondary hormone therapy, abiraterone and enzalutamide, has improved outcomes for metastatic castration-resistant prostate cancer (mCRPC) and prolonged patients’ lives significantly. Various studies have compared the cancer-related outcomes, adverse effects, and drug-induced comorbidities in patients with mCRPC who are treated with abiraterone or enzalutamide. However, few studies have explored associations between survival and comorbidities or comprehensive analyzed newly developed comorbidities during and after secondary hormone therapy. We attempted to clarify whether the Charlson comorbidity index (CCI) overall or itemized is predictive for overall survival, and we compared newly developed comorbidities between abiraterone and enzalutamide groups. We extracted data about expenses and comorbidities for patients who have mCRPC, received abiraterone and enzalutamide and met pre-examination operation criteria between September 2016 and December 2017 from the Taiwan National Health Insurance database. A total of 1153 patients with mCRPC who received abiraterone (n = 782) or enzalutamide (n = 371) with or without previous chemotherapy were included. We used the propensity score to match confounding factors, including age, pre-existing comorbidities, and precipitating factors for comorbidity (e.g., hypertension, hyperlipidemia), to eliminate selection bias in the comparison of newly developed comorbidities. Cox regression analysis was used for overall survival. We found that enzalutamide is superior to abiraterone with regard to overall survival. Our study revealed that there is no statistically significant difference in development of new comorbidities between abiraterone and enzalutamide group. Moreover, the CCI score, rather than any single item of the CCI, was a statistically significant predictor for overall survival.

scholarly journals Effectiveness of Vintage Hormone Therapy as Alternative Androgen Deprivation Therapy for Non-metastatic Castration-resistant Prostate Cancer

In Vivo ◽  
2021 ◽  
Vol 35 (2) ◽  
pp. 1247-1252
Author(s):  
HIROAKI IWAMOTO ◽  
HIROSHI KANO ◽  
TAKAFUMI SHIMADA ◽  
RENATO NAITO ◽  
TOMOYUKI MAKINO ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hormone Therapy ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Effect of the novel anti-androgen ARN-509 on response and seizure in castration-resistant prostate cancer models.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 28-28
Author(s):  
J. H. Hager ◽  
N. D. Smith ◽  
E. Bischoff ◽  
M. E. Jung ◽  
C. L. Sawyers ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Second Generation ◽  
Xenograft Model ◽  
Seizure Threshold ◽  
High Dose ◽  
Castration Resistant Prostate Cancer ◽  
Durable Response ◽  
Castration Resistant ◽  
Mouse Xenograft Model

28 Background: ARN-509 is a second-generation anti-androgen discovered in a screen to identify full androgen receptor (AR) antagonists in the context of AR over-expressing prostate cancer cells, a model for castration resistant prostate cancer (CRPC). It has been reported that other second-generation anti-androgens, MDV3100 and BMS-641988, can induce seizures at high dose in pre-clinical species and man and that this is mediated through antagonism of the CNS-based GABAA receptor. To define the clinical potential of ARN-509, we carried out a comprehensive assessment of its in vitro and in vivo activity in validated models of CRPC and assessed its seizure inducing potential. Methods: ARN-509 and MDV3100 were profiled in a series of assays to monitor both on- and off-target activity. Comparative in vivo efficacy in the LNCaP/AR mouse xenograft model of CRPC and pharmacokinetics were determined. Seizure inducing potential was assessed in an acute pentylenetetrazol (PTZ) infusion model. Results: In vivo, in the LNCaP/AR model of CRPC, an ARN-509 dose of 10 mg/kg/day exhibited tumors regressions equivalent in frequency and magnitude to a 30 mg/kg/day dose of MDV3100. Tumor re-growth following once daily dosing (30 mg/kg) for 28 days revealed that ARN-509 treated tumors exhibited a more durable response than MDV3100 treated tumors as evidenced by a significantly longer time to re-growth. At doses that yielded equivalent degree of tumor regression, the steady state plasma and brain levels were significantly lower for ARN-509 (10 mg/kg) than MDV3100 (30 mg/kg). ARN-509 and MDV3100 exhibit similar binding affinity to the GABAA receptor; IC50 3.0 and 2.7 mM, respectively. In vivo seizure potential of ARN-509 and MDV3100 was assessed in an acute PTZ infusion model in mice. MDV3100 was found to produce a dose dependant lowering of seizure threshold, while ARN-509 had no effect at any dose tested. Conclusions: ARN-509 is a second-generation anti-androgen with significant efficacy and an appropriate safety profile that supports its clinical development in both CRPC and earlier stages of prostate cancer. ARN-509 is currently in a phase I/II study in CRPC patients. [Table: see text]

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.

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