scholarly journals Prognostic value of ECOG performance status and Gleason score in the survival of castration-resistant prostate cancer: a systematic review

2020 ◽  
Vol 0 (0) ◽  
pp. 0
Author(s):  
Wen-Jun Chen ◽  
Da-Ming Kong ◽  
Liang Li
2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 84-84
Author(s):  
Susan F. Slovin ◽  
Karen E. Knudsen ◽  
Susan Halabi ◽  
Mark T. Fleming ◽  
Ana M. Molina ◽  
...  

84 Background: Loss of retinoblastoma tumor suppressor (RB) function has been shown to lead to CRPC and is strongly associated with poor outcome. RB functions as a transcriptional repressor; as such, loss of RB causes de-repression of pro-tumorigenic gene networks, including deregulation of the androgen receptor (AR) locus, excessive AR production, and castration-resistant (ligand independent) AR activity that can bypass hormone therapy. Our hypothesis is that leveraging RB status can direct treatment decisions. The primary objective of the trial (NCT02218606) was to determine the radiographic progression free survival (rPFS) of AA/prednisone (AAP) with and without CBZ in mCRPC patients (pts) that have progressed on primary androgen deprivation therapy and no prior AR directed therapy or chemotherapy. Methods: This is a multicenter non-comparative randomized phase 2 trial. Pts were randomized 1:1 to AAP with crossover to CBZ upon AAP failure (Arm 1), or the combination of AAP + CBZ (Arm 2). Randomization was stratified by the CALGB 90401 prognostic risk groups. The primary endpoint was rPFS (time from randomization to radiographic progression or death, whichever occurs first). Arms were analyzed separately. Results: Between October 2014 and March 2019, 93 pts were accrued; 81 were randomized. Median age was 68 years and ECOG performance status was 0 or 1. Endpoints are shown in Table. Therapies were well tolerated. Conclusions: Results of AAP + CBZ (Arm 2) in chemotherapy naïve pts suggest that men may derive benefit from the earlier use of CBZ with acceptable toxicity, supporting further study of this combination in mCRPC pts. Circulating Tumor Cells are being analyzed for changes in RB/AR expression. Managed by: Prostate Cancer Clinical Trials Consortium; Funding: Sanofi US; Support: Prostate Cancer Foundation. Clinical trial information: NCT02218606. [Table: see text]


2014 ◽  
Vol 8 (9-10) ◽  
pp. 583 ◽  
Author(s):  
Ravinder Clayton ◽  
Jackson Wu ◽  
Daniel Y Heng ◽  
Scott A North ◽  
Urban Emmenegger ◽  
...  

Introducton: The COU-AA-301 trial showed that abiraterone acetate (abiraterone), an oral cytochrome p450 CYP17 inhibitor, improved survival for men with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel. To better understand the non-clinical trial experience with abiraterone, we undertook a multicentre retrospective analysis of Canadian mCRPC patients treated with abiraterone.Methods: Consecutive patients with mCRPC who received abiraterone post-docetaxel were identified using centralized pharmacy records. These patients came from 5 Canadian tertiary cancer centres. Patients who received abiraterone for approved indications were included. Demographics, prognostic factors, treatment outcomes and adverse events were abstracted.Results: We included 187 patients who initiated abiraterone between January 2011 and June 2012. The median age at diagnosis and abiraterone start was 65 and 73 years, respectively. Seventy-three (39%) patients had metastatic disease at diagnosis. The Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 and 3 was noted in 17, 96, 39 and 8 patients, respectively. The median prostate-specific antigen (PSA) at abiraterone start was 132, with a median PSA doubling time of 2.8 months. The median follow-up of patients still on active follow-up was 13 months. The proportion of patients achieving a ≥50% PSA reduction was 64/177 (36%). PSA progression-free survival was 3.5 months (95% confidence interval [CI], 3.0, 4.0). Median overall survival from start of abiraterone was 11 months (95% CI, 8.0, 13) and 38 months (95% CI, 31, 41) from date of mCRPC. Anemia and fatigue were the most commonly reported adverse events.Conclusions: This study carries the inherent limitations of a retrospective chart review. The outcomes in this series of men treated with abiraterone in a non-trial setting were expected, considering previous clinical trials. Our results, therefore, support the generalizability of the COU-AA-301 study results.


2020 ◽  
pp. 107815522095161
Author(s):  
Özgecan Dülgar ◽  
Deniz Tataroğlu Özyükseler ◽  
Mustafa Başak ◽  
Seval Ay ◽  
Deniz Tural ◽  
...  

Objective Prostate cancer is the second leading cause of cancer death in men. Androgen deprivation therapy (ADT) has been the primary therapeutic approach for treatment of prostate cancer. However,nearly all patients develop the castration-resistant disease . We evaluated real-world data with abiraterone and enzalutamide treatment. By this data, we aimed to analyze whether that prior short response to ADT could predict response to subsequent therapy with androgen receptor axis targeted agent (ARATA). Material and Method We collected data from two cancer centers, 151 consecutive patients with treated abiraterone or enzalutamide in the first line of metastatic castration resistant prostat cancer (mCRPC) setting were included. The patients who received docetaxel in castration naive setting is also included. Time to castration resistance (TTCR) was defined as the duration from the initial to failure of primary ADT. Results Patients with treated ARATA were divided into two groups according to the time to castration resistance (TTCR). Patients who became resistant to ADT up to one year had a median PFS of 6.6 months, compared to median PFS of 13.3 months for patients who responded ADT for more than 1 year. (p = 0.002). In the post-docetaxel setting, median PFS is 12.6 months of patients with treated ARATA who had TTCR for more than one year, and median PFS is 6.6 months in those who had TTCR less than one year (p = 0.007).Univariate and multivariate analyses were performed to determine the clinical factors on ARATA outcomes. Eastern Cooperative Oncology Group (ECOG) performance status(PS), median prostate-specific antigen(PSA) and time to CRPC were significantly predicted outcomes of ARATA on multivariate analysis. Conclusion TTCR is also a predictor for PFS of the patients who were treated ARATA both whole cohort and post-docetaxel.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16524-e16524
Author(s):  
Manreet Randhawa ◽  
Robert J Jones ◽  
Irene Stratton ◽  

e16524 Background: Clinicians in 17 UK oncology centres comprise the National Radium-223 Dichloride Audit (NRDA) group which is evaluating treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 dichloride (Xofigo). Methods: Patients commencing treatment from 1st September 2017 were included. Clinical and laboratory parameters were collected throughout treatment. Analyses used frequency tables and univariate analysis. Results: As of February 2019, data from 400 patients has been collected. We report the outcomes on the first 150 patients who are evaluable. At first treatment, median age was 72 years (25th to 75th centile: 67-78), 54% of patients had an ECOG performance status (PS) of 1, 32.6% of patients had a WHO pain score of 1, 60% of patients had an ALP level of < 220U/L and 26% of patients received docetaxel for mCRPC. The mean number of cycles completed was 5. Sixty patients (40%) did not complete 6 cycles and 42/60 (70%) discontinued due to disease progression. Changes in variables between treatment 1 and 6 are shown in Table. Adverse events reported were fatigue (76%), diarrhoea (38%), nausea/vomiting (35%), constipation (32%), anaemia (28%), thrombocytopaenia (12%) and neutropaenia (5%). There was no overall change in ECOG PS. In those who completed quality of life (QOL) questionnaires at treatment 1 and 6 (58%), there was no difference. Conclusions: The ongoing NRDA Group records data from mCRPC patients treated across the UK in routine care. To our knowledge, it is the first prospective analysis of such patients and the largest in assessing treatment patterns and outcomes including QOL data as well as standard laboratory parameters. Disclosures: The NRDA Group has been funded by a research grant from Bayer.[Table: see text]


2020 ◽  
Vol 25 (11) ◽  
pp. 1881-1891
Author(s):  
Noriyoshi Miura ◽  
Keiichiro Mori ◽  
Hadi Mostafaei ◽  
Fahad Quhal ◽  
Reza Sari Motlagh ◽  
...  

Abstract Introduction This systematic review and meta-analysis aimed to assess the prognostic value of testosterone in patients with castration-resistant prostate cancer (CRPC). Materials and methods PubMed, Web of Science, and Scopus databases were systematically searched until December 2019, according to the Preferred Reporting Items for Systemic Review and Meta-analysis statement. The endpoints were progression-free survival (PFS) and overall survival (OS). Results We identified 11 articles with 4206 patients for systematic review and nine articles with 4136 patients for meta-analysis. Higher testosterone levels were significantly associated with better OS (pooled HR 0.74, 95% CI 0.58–0.95) and better PFS (pooled HR 0.51, 95% CI 0.30–0.87). Subgroup analyses based on the treatment type revealed that higher testosterone levels were significantly associated with better OS in CRPC patients treated with androgen receptor-targeted agents (ARTAs) (pooled HR 0.64, 95% CI 0.55–0.75), but not in those treated with chemotherapy (pooled HR 0.78, 95% CI 0.53–1.14). Conclusion This meta-analysis demonstrated that the PFS and OS were significantly greater in patients with CRPC in those with higher testosterone levels than that of those with lower testosterone levels. In the subgroup analyses, lower testosterone levels were a consistently poor prognostic factor for OS in patients treated with ARTAs, but not in those treated with chemotherapy. Therefore, higher testosterone levels could be a useful biomarker to identify patient subgroups in which ARTAs should be preferentially recommended in the CRPC setting.


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