Role of novel hormonal therapies in the management of non-metastatic castration-resistant prostate cancer: a literature-based meta-analysis of randomized trials

2019 ◽  
Vol 22 (7) ◽  
pp. 1033-1039 ◽  
Author(s):  
G. Roviello ◽  
M. R. Gatta Michelet ◽  
A. D’Angelo ◽  
S. Nobili ◽  
E. Mini
Keyword(s):  
Prostate Cancer ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Hormonal Therapies

Meta-analysis of randomized trials to study the impact of prednisone on toxicities and survival in metastatic castration-resistant prostate cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 28-28
Author(s):  
Gurudatta Naik ◽  
Charity Morgan ◽  
Matt D. Galsky ◽  
William K. Oh ◽  
Guru Sonpavde
Keyword(s):  
Prostate Cancer ◽  
Randomized Trials ◽  
Data Extraction ◽  
Meta Analysis ◽  
Oral Prednisone ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Number Of Patients ◽  
Meta Analyses ◽  
The Impact

28 Background: The impact of daily oral prednisone (P) on toxicities and outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) is unclear. We conducted a meta-analysis of randomized trials comparing regimens that included P in only one arm. Methods: PubMed, conferences and clinicaltrials.gov databases were searched for articles reported from January 1966 to June 2013. Eligible studies were selected in an unbiased manner and limited to randomized trials enrolling patients with mCRPC and comparing regimens administering P in only one arm. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Arms containing P were compared with arms without P for severe toxicities grade 3 or higher and overall survival (OS). Results: Five randomized trials were published or presented with P in only one arm: by Scher and colleagues comparing docetaxel (D) plus P versus D plus DN101 (n=953), by Higano and colleagues comparing DP versus GVAX (n=621), by Small and colleagues comparing DP versus GVAX plus D (n=394), by Fossa and colleagues comparing P versus flutamide (n=201) and by Petrylak and colleagues comparing mitoxantrone plus P versus D plus estramustine phosphate (n=770). The total number of patients was 2,939, of whom 1,471 received therapy not containing P and 1,468 received therapy containing P. All five trials were eligible for analysis of toxicities, but the Fossa trial was excluded for the OS analysis due to lack of required parameters. There was no difference between the non-P and P groups for severe toxicities (incidence rate ratio [IRR] = 0.82, p = 0.712, I2 = 97.9%). When examining toxicities as a reason for discontinuing therapy, the non-P groups were not different from the P groups (relative risk [RR] = 1.24, p = 0.413, I2 = 86.8%). The non-P groups demonstrated no difference in OS compared to the P groups (HR = 1.09, p = 0.531, I2= 79.7%). The meta-analysis is limited by the trial level design and small number of patients and does not exclude a favorable palliative impact of P. Conclusions: This meta-analysis of randomized trials in mCRPC suggests no significant impact on severe toxicities and OS with the use of daily oral prednisone.

scholarly journals Prognostic role of chromogranin A in castration-resistant prostate cancer: A meta-analysis

2018 ◽  
Vol 20 (6) ◽  
pp. 561 ◽  
Author(s):  
Xue-Song Li ◽  
Li-Qun Zhou ◽  
Peng Hong ◽  
Run-Qi Guo ◽  
Gang Song ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromogranin A ◽  
Meta Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Prognostic Role ◽  
Castration Resistant

scholarly journals A Systematic Review and Meta-Analysis of Randomized Controlled Trials With Novel Hormonal Therapies for Non-Metastatic Castration-Resistant Prostate Cancer: An Update From Mature Overall Survival Data

2021 ◽  
Vol 11 ◽  
Author(s):  
Martina Maggi ◽  
Stefano Salciccia ◽  
Francesco Del Giudice ◽  
Gian Maria Busetto ◽  
Ugo G. Falagario ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Data ◽  
Interim Analysis ◽  
Meta Analysis ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Hormonal Therapies ◽  
Term Analysis

IntroductionTo get better insight into the management of non-metastatic castration-resistant prostate cancer (M0 CRPC), in this meta-analysis and review we aimed to present an updated evaluation of the efficacy and safety of novel hormonal therapies (nHT) for M0 CRPC according to final analyses with mature overall survival (OS) and safety data.MethodsWe analyzed metastasis-free survival (MFS), OS, time to prostate-specific antigen (PSA) progression, second-line therapies data, adverse events (AEs), including all AEs, serious AEs (SAEs), AEs leading to discontinuation of trial regimen, AEs leading to death, fatigue, dizziness, cardiovascular events, and fractures; moreover, we evaluated the impact of PSA doubling time (PSA-DT), Eastern Cooperative Oncology Group (ECOG) score, use of bone-targeted therapy, lymph lodes (LN) status, and prior HT on final OS data. A comparison among the placebo arms of the included trials in terms of survival and safety profiles was assessed.ResultsAccording to the pooled analysis with updated and mature OS data, OS was significantly improved with nHT compared to placebo (hazard ratio (HR)= 0.74, 95% confidence interval (CI)= 0.66–0.84). nHT significantly improved OS over placebo across all pre-specified subgroups. Subgroup analysis revealed a greater OS benefit in patients with PSA-DT >6 months than ≤6 months (HR= 0.69 versus HR= 0.75), ECOG 0 than 1 (HR= 0.70 versus HR= 0.80), N1 disease than N0 (HR= 0.61 versus HR= 0.78), and in those receiving bone-targeted therapy (HR= 0.65 versus HR= 0.74), and a comparable OS by number of prior HT (HR= 0.75 versus HR= 0.76, for HT= 1 and ≥2); yet, differences between pre-specified subgroups were not significant (all p> 0.05). Overall, the nHT arm was significantly associated with higher rates of AEs, when compared with the placebo arm. The long-term analysis showed a worse safety profile with nHT than the interim analysis.ConclusionsAccording to final analyses, nHT have shown to improve OS over placebo in the setting of high-risk M0 CRPC. The long-term analysis showed a worse safety profile with nHT than the interim analysis, whit distinct profiles among different nHT. The lack of survival data regarding second-line therapies remains a major issue.

AR Copy Number and AR Signaling-directed Therapies in Castrationresistant Prostate Cancer

2018 ◽  
Vol 18 (9) ◽  
pp. 869-876
Author(s):  
Samanta Salvi ◽  
Vincenza Conteduca ◽  
Cristian Lolli ◽  
Sara Testoni ◽  
Valentina Casadio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Copy Number ◽  
Clinical Trial Design ◽  
Complete Information ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Anti Cancer ◽  
Hormone Sensitive ◽  
Predictive And Prognostic Biomarker

Background: Adaptive upregulation of Androgen Receptor (AR) is the most common event involved in the progression from hormone sensitive to Castration-Resistant Prostate Cancer (CRPC). AR signaling remains the main target of new AR signalling-directed therapies such as abiraterone and enzalutamide in CRPC patients. Objective: In this review, we discuss general mechanisms of resistance to AR-targeted therapies, with a focus on the role of AR Copy Number (CN). We reported methods and clinical applications of AR CN evaluation in tissue and liquid biopsy, thus to have a complete information regarding its role as predictive and prognostic biomarker. Conclusion: Outcomes of CRPC patients are reported to be highly variable as the consequence of tumor heterogeneity. AR CN could contribute to patient selection and tumor monitoring in CRPC treated with new anti-cancer treatment as abiraterone and enzalutamide. Further studies to investigate AR CN effect to these agents and its potential combination with other prognostic or predictive clinical factors are necessary in the context of harmonized clinical trial design.

scholarly journals Interplay Between SOX9, Wnt/β-Catenin and Androgen Receptor Signaling in Castration-Resistant Prostate Cancer

2019 ◽  
Vol 20 (9) ◽  
pp. 2066 ◽  
Author(s):  
Namrata Khurana ◽  
Suresh C. Sikka
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Signaling Pathways ◽  
Critical Role ◽  
Castration Resistant Prostate Cancer ◽  
Form Complex ◽  
Androgen Receptor Signaling ◽  
Castration Resistant ◽  
Signaling Axis

Androgen receptor (AR) signaling plays a key role not only in the initiation of prostate cancer (PCa) but also in its transition to aggressive and invasive castration-resistant prostate cancer (CRPC). However, the crosstalk of AR with other signaling pathways contributes significantly to the emergence and growth of CRPC. Wnt/β-catenin signaling facilitates ductal morphogenesis in fetal prostate and its anomalous expression has been linked with PCa. β-catenin has also been reported to form complex with AR and thus augment AR signaling in PCa. The transcription factor SOX9 has been shown to be the driving force of aggressive and invasive PCa cells and regulate AR expression in PCa cells. Furthermore, SOX9 has also been shown to propel PCa by the reactivation of Wnt/β-catenin signaling. In this review, we discuss the critical role of SOX9/AR/Wnt/β-catenin signaling axis in the development and progression of CRPC. The phytochemicals like sulforaphane and curcumin that can concurrently target SOX9, AR and Wnt/β-catenin signaling pathways in PCa may thus be beneficial in the chemoprevention of PCa.

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