Androgen deprivation therapy and statin therapy in prostate cancer patients.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 205-205
Author(s):  
Kin Chung Lai ◽  
Toiya Turknett ◽  
Parminder Singh
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Deprivation Therapy ◽  
Cox Regression ◽  
Androgen Deprivation ◽  
P Value ◽  
Primary Therapy ◽  
Significant Difference ◽  
Chi Squared ◽  
Statin Use

205 Background: Metastatic prostate cancer (mPC) is treated with androgen deprivation therapy( ADT). Duration of response to ADT predicts patient’s survival. It has been shown in observational studies that concurrent statin use may prolong response to ADT. Studies in mice have shown negative interactions. We wanted to examine the effect of this interaction in patients being followed at Mayo Clinic Arizona (MCA). Methods: We examined 441 patients with mPC, who received ADT and were treated at MCA from year 2011 to 2017. . Our study evaluated the time to progression (TTP) and overall survival(OS) for patients with mPC on ADT with or without concurrent statin use. Among the patients who were evaluated, there was a subset of 156 patients taking abiraterone (ABI). Characteristics were compared between statin users and nonusers using Chi squared test and Wilcoxon rank-sum tests. The primary outcome was TTP defined as the duration from ADT initiation to disease progression. The association between statin use and TTP was analyzed by multivariable Cox regression to estimate hazard ratios (HRs) and 95% Conference Interval (CI), and adjusted for Gleason score, primary therapy type, prior ADT, metastatic status, and PSA at ADT initiation. Results: There was no significant difference in TTP when comparing patients with statin to those without a statin. The HR for statin use vs no statin use is 1.049 with CI (0.838, 1.314) and p-value is 0.677. There was no significant difference in overall survival when comparing statin vs no statin use. The HR for statin use vs no statin use was 0.928(CI 0.642, 1.342) with p-value at 0.693. In the ABI population, there was no significant difference in TTP for patients with statin vs no statin. HR was 1.00 CI (0.725, 1.377) with p-value at 0.998. For overall survival, there was no significant difference with HR at 0.852 (CI 0.502, 1.446) with p-value at 0.553. Conclusions: Despite retrospective studies showing benefit of use of statin in men with prostate cancer, our study observed no difference in long term outcomes. Possible explanations could be smaller sample size, inability to verify data as medication intake was not verified directly. Also, patient’s compliance with medications could be a confounding variable.

Duration of androgen deprivation therapy in high risk prostate cancer: Final results of a randomized phase III trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5008-5008 ◽  
Author(s):  
Abdenour Nabid ◽  
Marie-Pierre Garant ◽  
André-Guy Martin ◽  
Jean-Paul Bahary ◽  
Celine Lemaire ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Androgen Deprivation Therapy ◽  
Cox Regression ◽  
Mixed Linear Model ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
High Risk Prostate Cancer ◽  
Significant Difference ◽  
Risk Prostate Cancer

5008 Background: Long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) is a standard treatment for patients with high-risk prostate cancer (HRPC). However, the optimal duration of ADT is not yet defined. The aim of this randomized trial (Clinical Trials.gov, #NCT00223171) was to compare outcomes of RT combined with either 36 or 18 months of ADT. Methods: Patients with HRPC were randomized to pelvic and prostate RT combined with 36 (arm 1) or 18 months (arm 2) of ADT. Overall survival (OS) and quality of life (QoL) were primary end points. OS rates were compared with Cox Regression model and QoL data were analyzed through mixed linear model. Results: 630 patients were randomized, 310 to arm 1 and 320 to arm 2. With a median follow-up of 9.4 years, 290 patients had died (147 arm 1 vs. 143 arm 2). The 10-year OS rate was 62.4% (95% confidence interval [CI] 56.4%, 67.8%) for arm 1 and 62.0% (95% CI 56.1%, 67.3%) for arm 2 (p = 0.8412) with a global hazard ratio (HR) of 1.024 (95% CI 0.813-1.289, p = 0.8411). QoL analysis showed a significant difference (p < 0.001) in 6 scales and 13 items favoring 18 months ADT with two of them presenting a clinically relevant difference in mean scores of ≥10 points. Conclusions: In HRPC, ADT combined with RT can be safely reduced from 36 to 18 months without compromising outcomes or QoL. 18 months of ADT represents a new standard of care in HRPC. Funded by AstraZeneca Pharmaceuticals Clinical trial information: NCT00223171.

Correlation between time to prostate cancer metastasis and overall survival after androgen-deprivation therapy initiation.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 250-250
Author(s):  
Loana Bueno Valenca ◽  
Lillian Werner ◽  
Wanling Xie ◽  
Mari Nakabayashi ◽  
Philip W. Kantoff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Deprivation Therapy ◽  
Cancer Metastasis ◽  
Cox Regression ◽  
Rank Correlation ◽  
Androgen Deprivation ◽  
Castration Resistance ◽  
Castration Resistant ◽  
Prostate Cancer Metastasis

250 Background: Currently,overall survival (OS) is used to determine treatment efficacy in trials for advanced prostate cancer (PC). Reliable intermediate endpoints could hasten drug development efforts. We therefore sought to determine the association between an intermediate endpoint—time to metastasis (TTM)—and OS in PC patients receiving androgen deprivation therapy (ADT) for biochemical recurrence (BCR). Methods: The Dana-Farber PC database identified 415 patients who received ADT for non-metastatic BCR with median 6.4 years follow-up. Associations between TTM and OS were measured from (i) time of ADT initiation (n=398) and (ii) time of castration-resistance (n=247) using a non-parametric Kendall tau rank correlation for bivariate time to event outcomes. A Cox regression model was used to assess the association of development of metastasis and OS for landmark timepoints. Results: Among 398 subjects analyzed from start of ADT, 180 (45%) developed metastases with median TTM 6.25 years. A total of 152 (38%) died, with a median OS of 8.5 years. For men developing metastases within five years of ADT initiation, hazard ratio (HR) for mortality was 7.42 (p<0.0001, 95% CI 4.18-13.17). Among 247 subjects assessed from time of castration resistant PC (CRPC), 172 (70%) developed metastases with a median TTM 2.6 years. In this subgroup, 140 (56%) patients died with median OS 5.25 years. For men developing metastases within three years of developing castration-resistance, HR for mortality was 5.25 (p<0.0001, 95% CI 3.20-8.61). Overall, correlation between TTM and OS from ADT initiation and OS was 0.25 (P<0.0001, 95% CI 0.20-0.29). Correlation between TTM and OS from CRPC was 0.32 (P<0.0001, 95% CI 0.25-0.37). Conclusions: TTM was significantly correlated with OS in PC patients treated with ADT for BCR. Prospective data in a large validation cohort will help determine whether TTM is suitably predictive of OS to serve as a primary endpoint in clinical trials.

Age-dependent overall survival benefit of androgen deprivation therapy for metastatic prostate cancer

2019 ◽  
Vol 25 (8) ◽  
pp. 1927-1932 ◽  
Author(s):  
Matthew J Keating ◽  
Lisa Giscombe ◽  
Toufic Tannous ◽  
Nishitha Reddy ◽  
Shiva Kumar R Mukkamalla ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Deprivation Therapy ◽  
Survival Benefit ◽  
Metastatic Prostate Cancer ◽  
Androgen Deprivation ◽  
National Cancer Database ◽  
Younger Patients ◽  
Significant Difference ◽  
Overall Survival Benefit

Background Androgen deprivation therapy (ADT) remains a standard of care in metastatic prostate cancer. Recent prospective trials have explored addition of chemotherapy to ADT. We retrospectively examined overall survival in metastatic prostate cancer patients treated with ADT, chemotherapy plus ADT (C + ADT), or observation from 2004 to 2010 using National Cancer Database data. Methods Using the National Cancer Database, 21,977 patients with metastatic prostate cancer diagnosed from 2004 to 2010 were identified. Multivariate logistic regression, Kaplan-Meier survival analysis and Cox proportional hazards regression modeling were implemented, with overall survival as the primary endpoint. Results Five-year overall survival was 13.6% in patients aged ≥ 75 years vs. 30.1% (age 65–74) and 34.5% (age 18–64). Subgroup analysis of age-based cohorts (<65 and ≥65 years) showed poor overall survival for C + ADT vs. ADT alone, both in younger (HR 1.35, 95% CI 1.21–1.50; p < 0.0001) as well as older (HR 1.21, 95% CI 1.08–1.34; p = 0.0006) populations. Younger patients had no significant difference in overall survival for observation vs. ADT (HR 0.99, 95% CI 0.92–1.08; p = 0.9121). Besides age, other factors impacting overall survival included race, rural/urban settings, comorbidity score, income, PSA and radiation. Discussion Younger patients had no significant difference in overall survival between observation or ADT. This implies a group of younger patients in whom ADT does not confer any overall survival benefit. Future clinical trials with genetic and biologic markers are needed to delineate which subgroups would not benefit from C + ADT or ADT alone. This is of utmost clinical importance given the negative impact of ADT on quality of life and comorbidities.

scholarly journals Next-generation androgen receptor inhibitors in non-metastatic castration-resistant prostate cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592097813
Author(s):  
Pernelle Lavaud ◽  
Clément Dumont ◽  
Constance Thibault ◽  
Laurence Albiges ◽  
Giulia Baciarello ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Receptor ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Next Generation ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Recent Advances

Until recently, continuing androgen deprivation therapy (ADT) and closely monitoring patients until evolution towards metastatic castration-resistant prostate cancer (CRPC) were recommended in men with non-metastatic CRPC (nmCRPC). Because delaying the development of metastases and symptoms in these patients is a major issue, several trials have investigated next-generation androgen receptor (AR) axis inhibitors such as apalutamide, darolutamide, and enzalutamide in this setting. This review summarizes the recent advances in the management of nmCRPC, highlighting the favourable impact of next-generation AR inhibitors on metastases-free survival, overall survival and other clinically meaningful endpoints.

scholarly journals NRG1 Genetic Variant Influences the Efficacy of Androgen-Deprivation Therapy in Men with Prostate Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 528
Author(s):  
Shu-Pin Huang ◽  
Yei-Tsung Chen ◽  
Lih-Chyang Chen ◽  
Cheng-Hsueh Lee ◽  
Chao-Yuan Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Tyrosine Kinases ◽  
Multiple Testing ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Androgen Deprivation ◽  
Nucleotide Polymorphisms ◽  
Multiple Testing Correction ◽  
Cancer Specific Survival

Neuregulins (NRGs) activate receptor tyrosine kinases of the ErbB family, and play essential roles in the proliferation, survival, and differentiation of normal and malignant tissue cells. We hypothesized that genetic variants of NRG signalling pathway genes may influence treatment outcomes in prostate cancer. To test this hypothesis, we performed a comprehensive analysis to evaluate the associations of 459 single-nucleotide polymorphisms in 19 NRG pathway genes with cancer-specific survival (CSS), overall survival (OS), and progression-free survival (PFS) in 630 patients with prostate cancer receiving androgen-deprivation therapy (ADT). After multivariate Cox regression and multiple testing correction, we found that NRG1 rs144160282 C > T is significantly associated with worsening CSS, OS, and PFS during ADT. Further analysis showed that low expression of NRG1 is closely related to prostate cancer, as indicated by a high Gleason score, an advanced stage, and a shorter PFS rate. Meta-analysis of 16 gene expression datasets of 1,081 prostate cancer samples and 294 adjacent normal samples indicate lower NRG1 expression in the former compared with the latter (p < 0.001). These results suggest that NRG1 rs144160282 might be a prognostic predictor of the efficacy of ADT. Further studies are required to confirm the significance of NRG1 as a biomarker and therapeutic target for prostate cancer.

Androgen deprivation therapy and risk of SARS-CoV-2 infection in men with prostate cancer: A University of California (UC) Health System registry study.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 37-37
Author(s):  
Daniel Kwon ◽  
Rohit Vashisht ◽  
Hala Borno ◽  
Rahul Raj Aggarwal ◽  
Eric Jay Small ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Health System ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Host Cells ◽  
University Of California ◽  
Registry Study ◽  
Medical Centers ◽  
Chi Squared ◽  
The University

37 Background: SARS-CoV-2 entry into host cells is facilitated by the transmembrane protease TMPRSS2. TMPRSS2 expression can be modulated by the androgen receptor. It is unclear whether androgen deprivation therapy (ADT) may partially protect from SARS-CoV-2 infection. Methods: A retrospective registry study of adult men with prostate cancer who underwent testing for SARS-CoV-2 in the UC Health System between February 1, 2020 and October 6, 2020 was performed. The University of California Health COVID Research Data Set (UC CORDS), which includes electronic health data of all patients who underwent testing for SARS-CoV-2 at 5 UC academic medical centers (UC Davis, UC Irvine, UC Los Angeles, UC San Diego, and UC San Francisco) and 12 affiliated hospitals across California, was used. Association of SARS-CoV-2 infection and receipt of ADT (GnRH agonist or antagonist) within 90 days of COVID testing was determined using the Chi-Squared test. Analyses (Chi-Squared or Fisher’s exact tests) were also performed in race/ethnicity subgroups. Results: Overall, 2,948 men with prostate cancer who underwent SARS-CoV-2 testing were identified, of whom 59 (2.0%) tested positive. Of the 2,948 men, 2,124 (72%) were White; 219 (7%) Black or African-American; 182 (6%) Asian or Native Hawaiian/Pacific-Islander; 176 (6%) Other race; and 247 (8%) Unknown race. There were 235 (8%) Hispanic or Latino men. Among the 444 men who received ADT in the entire cohort, 7 (1.6%) tested positive, and among the 2,504 men who did not receive ADT, 52 (2.1%) tested positive (OR 0.76, 95% CI 0.34-1.67, P = 0.49). No statistically significant association between ADT and SARS-CoV-2 positivity was found within race or ethnicity subgroups. Conclusions: No association between the use of ADT and the risk of testing positive for SARS-CoV-2 was identified in this study of a diverse patient population in the University of California Health System medical centers and hospitals. In this setting of an overall low prevalence of SARS-CoV-2 infection, thus far, there is no strong evidence of a protective benefit of ADT.

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