Chromogranin A and neurone-specific enolase serum levels as predictors of treatment outcome in patients with metastatic castration-resistant prostate cancer undergoing abiraterone therapy

2016 ◽  
Vol 119 (1) ◽  
pp. 30-37 ◽  
Author(s):  
Matthias M. Heck ◽  
Markus A. Thaler ◽  
Sebastian C. Schmid ◽  
Anna-Katharina Seitz ◽  
Robert Tauber ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Outcome ◽  
Chromogranin A ◽  
Serum Levels ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Treatment Outcome, Toxicity, and Predictive Factors for Radioligand Therapy with 177Lu-PSMA-I&T in Metastatic Castration-resistant Prostate Cancer

2019 ◽  
Vol 75 (6) ◽  
pp. 920-926 ◽  
Author(s):  
Matthias M. Heck ◽  
Robert Tauber ◽  
Sebastian Schwaiger ◽  
Margitta Retz ◽  
Calogero D’Alessandria ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Outcome ◽  
Predictive Factors ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Castration Resistant

scholarly journals Oligometastatic Prostate Adenocarcinoma. Clinical-Pathologic Study of a Histologically Under-Recognized Prostate Cancer

2020 ◽  
Vol 10 (4) ◽  
pp. 265 ◽  
Author(s):  
Claudia Manini ◽  
Alba González ◽  
David Büchser ◽  
Jorge García-Olaverri ◽  
Arantza Urresola ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Local Control ◽  
Chromogranin A ◽  
Prostate Adenocarcinoma ◽  
Fisher Exact Test ◽  
Castration Resistant Prostate Cancer ◽  
Ki 67 ◽  
Pgp 9.5 ◽  
Castration Resistant ◽  
Therapeutic Decisions

The clinical parameters and the histological and immunohistochemical findings of a prospective protocolized series of 27 prostate carcinoma patients with oligometastatic disease followed homogeneously were analyzed. Lymph nodes (81.5%) and bones (18.5%) were the only metastatic sites. Local control after metastatic directed treatment was achieved in 22 (81.5%) patients. A total of 8 (29.6%) patients developed castration-resistant prostate cancer. Seventeen (63%) patients presented with non-organ confined disease. The Gleason index 8–10 was the most frequently observed (12 cases, 44.4%) combined grade. Positive immunostainings were detected with androgen receptor (100%), PGP 9.5 (74%), ERG (40.7%), chromogranin A (29.6%), and synaptophysin (18.5%) antibodies. The Ki-67 index value > 5% was observed in 15% of the cases. L1CAM immunostaining was negative in all cases. Fisher exact test showed that successful local control of metastases was associated to mild inflammation, organ confined disease, Ki-67 index < 5%, and Gleason index 3 + 3. A castration resistant status was associated with severe inflammation, atrophy, a Gleason index higher than 3 + 3, Ki-67 index ≥ 5%, and positive PGP 9.5, chromogranin A, and synaptophysin immunostainings. In conclusion, oligometastatic prostate adenocarcinoma does not have a specific clinical-pathologic profile. However, some histologic and immunohistochemical parameters of routine use may help with making therapeutic decisions.

scholarly journals Reinduction of Hormone Sensitivity to Goserelin following Chemotherapy with Vinorelbine in Castration-Resistant Prostate Cancer

2010 ◽  
Vol 10 ◽  
pp. 1814-1817
Author(s):  
Tal Grenader ◽  
Anthony Goldberg
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Serum Levels ◽  
Symptomatic Improvement ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Luteinizing Hormone Releasing Hormone ◽  
Androgen Ablation ◽  
Castration Resistant ◽  
Cessation Of Treatment

Primary androgen ablation leads to symptomatic improvement and a reduction in prostate-specific antigen (PSA) serum levels in patients with advanced prostate cancer, but all patients eventually become refractory to hormone therapy with progression of the disease and a life expectancy of about a year. We describe a patient who developed castration resistance, was treated with vinorelbine, and continues to be progression free on therapy with luteinizing hormone releasing hormone agonists alone, more than 2.5 years following cessation of treatment with vinorelbine.

Comprehensive analysis of serum chromogranin A and neuron‐specific enolase levels in localized and castration‐resistant prostate cancer

2020 ◽  
Vol 127 (1) ◽  
pp. 44-55 ◽  
Author(s):  
Tibor Szarvas ◽  
Anita Csizmarik ◽  
Tamás Fazekas ◽  
András Hüttl ◽  
Péter Nyirády ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromogranin A ◽  
Neuron Specific Enolase ◽  
Comprehensive Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Association between circulating miRNA-141 and miRNA-375 and treatment outcome in metastatic castration-resistant prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16507-e16507 ◽  
Author(s):  
Ahmed Hussien Zedan ◽  
Palle Jörn Sloth Osther ◽  
Jannie Assenholt ◽  
Jonna Skov Madsen ◽  
Torben Hansen
Keyword(s):  
Prostate Cancer ◽  
Treatment Outcome ◽  
Plasma Levels ◽  
Cox Regression ◽  
Prognostic Models ◽  
Castration Resistant Prostate Cancer ◽  
High Baseline ◽  
Castration Resistant ◽  
Prognostic Importance ◽  
Baseline Levels

e16507 Background: Metastatic castration resistant prostate cancer (mCRPC) is associated with high mortality. Monitoring of disease activity at this stage, with lack of validated prognostic models, is still a major clinical challenge. The role of microRNAs (miRNAs) has been widely investigated in prostate cancer with both diagnostic and prognostic potential. The aim of this study was to investigate the relationship between circulating miRNAs and treatment outcome in mCRPC patients. Methods: The relative expression of four miRNAs was investigated in plasma samples from 84 mCRPC patients; 40 patients were treated with docetaxel and 44 patients with abiraterone. Real-time polymerase chain reaction was used for analysis. Blood was sampled at baseline, before the second treatment cycle, and at radiological progression (RP). Associations to prognoses were analyzed using the Cox Regression analyses. Results: The plasma levels of all four miRNAs decreased significantly after treatment initiation in patients receiving docetaxel, and for miRNA-141 and miRNA-375 the level increased again at the time of RP. High baseline levels of miRNA-141 were significantly associated with a shorter time to RP in patients receiving both abiraterone, hazard ratio (HR) 3.18 (95% confidence interval (CI) 1.31-7.32), p < 0.01, and docetaxel HR 2.56 (95% CI 1.45-4.50), p < 0.01, and a shorter overall survival (OS), HR 3.20 (95% CI 1.25-9.37), p = 0.02, and HR 1.77 (95% CI 1.07-2.83), p = 0.02, respectively. Likewise, high baseline levels of miRNA-375 were also significantly associated with a shorter time to RP in both cohorts and OS in patients receiving docetaxel. Conclusions: Plasma levels of miRNA-141 and miRNA-375 were of prognostic importance in patients with mCRPC receiving both abiraterone and docetaxel and may be used in treatment monitoring irrespective of treatment modality.

scholarly journals Treatment outcome of docetaxel plus prednisolone for metastatic castration-resistant prostate cancer in Korea

2014 ◽  
Vol 10 (2) ◽  
pp. 251 ◽  
Author(s):  
KangHyun Lee ◽  
In-Chang Cho ◽  
JaeYoung Joung ◽  
HoKyung Seo ◽  
Jinsoo Chung ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Outcome ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Improving the Outcome of Patients with Castration-resistant Prostate Cancer Through Rational Targeting of the Androgen Receptor

2009 ◽  
Vol 05 (01) ◽  
pp. 58
Author(s):  
Gerhardt Attard ◽  
Johann S De Bono ◽  
Chris Parker ◽  
◽  
◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Significant Proportion ◽  
Serum Levels ◽  
Castration Resistant Prostate Cancer ◽  
Common Cause ◽  
Receptor Signalling ◽  
Castration Resistant ◽  
Prostate Cancers ◽  
Related Mortality

Castration-resistant prostate cancer (CRPC) is now the second most common cause of male cancer-related mortality. Recent evidence confirms that androgen receptor signalling continues to drive a significant proportion of progressing prostate cancers despite castrate serum levels of testosterone and multiple hormonal interventions. An increased understanding of the molecular biology underlying CRPC is informing on therapeutic targets for this disease, and we hypothesise that this will lead to the development of more efficacious drugs.

Lessons learned from the metastatic castration-resistant prostate cancer phase I trial of EPI-506, a first-generation androgen receptor N-terminal domain inhibitor.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 257-257 ◽  
Author(s):  
Ronan Le Moigne ◽  
Han-Jie Zhou ◽  
Jon K. Obst ◽  
C. Adriana Banuelos ◽  
Kunzhong Jian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Phase 1 ◽  
Serum Levels ◽  
Lessons Learned ◽  
Plasma Samples ◽  
Castration Resistant Prostate Cancer ◽  
Terminal Domain ◽  
Castration Resistant

257 Background: Aniten compounds bind to the N-terminal domain (NTD) of the androgen receptor (AR) and inhibit AR dependent transcription. EPI-506, the pro-drug of EPI-002, was the first AR NTD inhibitor tested in a Phase 1 study in men with metastatic castration-resistant prostate cancer (mCRPC). The drug was well-tolerated but required high doses. At doses >1280 mg, EPI-506 treatment resulted in PSA declines; however, these were minor and of short duration, reflecting EPI-506’s low potency and short half-life. To understand EPI-506’s metabolic vulnerabilities, patient plasma samples were analyzed to identify metabolites. Methods: PSA serum levels were assessed after a month of dosing. Patient plasma samples were analyzed and pharmacokinetic (PK) parameters calculated. Three plasma samples from patients (one 80 and two 3,600 mg doses), were pooled across timepoints and metabolites were analyzed. EPI-506 metabolism was assessed in in vitro ADME assays and metabolite activity was measured. Results: EPI-002 patient plasma profiles exhibited dose-proportional Cmax and AUC following once or twice-daily EPI-506 administration. PSA declines (range of 8-29%) were observed, especially at higher doses (≥ 1,280 mg). A total of 19 metabolites were identified. Metabolite M19, a glycerol-moiety oxidant, was the major drug-related component. Other metabolic pathways included O-glucuronidation, sulfation, carboxylic acid formation, and oxidative chlorine loss. The major metabolites were tested in an AR driven reporter assay and were shown to be inactive. Interestingly, in vitro ADME assays predicted glucuronidation and sulfation but not cytochrome dependent metabolism. Conclusions: EPI-506 was tested in a phase 1 trial and showed minor PSA declines. The drug was well-tolerated but was highly metabolized. Patient plasma samples identified 19 metabolites. Newer molecules have been synthesized to address EPI-002’s metabolic liabilities and demonstrate > 20-fold improved potency and higher stability. These next generation Anitens are currently being characterized for IND filing. Clinical trial information: NCT02606123.

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