Use of germ-line single nucleotide polymorphisms (SNPs) in drug transporters (ABCG2/ABCB1) and tubulin (TUBB4) to predict survival in patients with metastatic castrate-resistant prostate cancer (CRPC) receiving docetaxel.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 58-58
Author(s):  
N. M. Hahn ◽  
J. Jung ◽  
S. Philips ◽  
Y. R. Patel ◽  
K. A. Carr ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Germ Line ◽  
Treatment Options ◽  
Specific Antigen ◽  
Cancer Center ◽  
Clinical Parameters ◽  
Nucleotide Polymorphisms ◽  
Multiple Treatment ◽  
Castrate Resistant ◽  
Ecog Ps

58 Background: Multiple treatment options now exist for metastatic CRPC patients (pts). Germ-line SNPs in docetaxel (D) transport, metabolism, binding site, and degradation genes may contribute to variability in outcomes observed in D treated CRPC pts. Methods: Between 1/07 and 10/08, all PCa pts seen in the Indiana University Simon Cancer Center oncology clinics were approached for recruitment to the Prostate Cancer Genetic Risk Evaluation of SNPs Study (PROGRESS). Participants completed a demographic and clinical questionnaire and provided a blood sample. Only CRPC pts treated with D were included in this analysis. Germ-line DNA was analyzed for SNP genotyping on a 128-SNP chip using a TaqMan OpenArray GT Kit (Applied Biosystems). The chip included genes critical to D signaling, transport, and elimination with minor allele frequencies > 5%. Pts were followed for progression-free (PFS) and overall survival (OS). Univariable analyses were performed to identify significant associations between SNP genotype, clinical parameters, and PFS and OS outcomes. Results: 60 pts with metastatic CRPC initiated on D enrolled. Demographics included: age (median) – 69 yrs, ECOG PS 0– 40%, prostate specific antigen (PSA) (median) – 129.9 ng/ml, PSA doubling time (median) – 1.8 months, visceral mets –25%. No clinical parameters were associated with PFS and OS. Significant SNP associations are summarized below. Conclusions: Differences in germ-line ABCG2, ABCB1, and TUBB4 SNPs may contribute to variation in clinical outcomes in CRPC pts treated with D. [Table: see text] [Table: see text]

Germ-line single nucleotide polymorphism (SNP) predictors of progression-free survival and overall survival in patients with advanced prostate cancer treated with androgen-deprivation therapy (ADT).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 51-51 ◽  
Author(s):  
M. T. Campbell ◽  
J. Jung ◽  
S. Philips ◽  
Y. Mohammadi ◽  
K. A. Carr ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Clinical Outcomes ◽  
Germ Line ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Clinical Parameters ◽  
Free Survival ◽  
Hormone Synthesis

51 Background: Significant variation in response duration and overall survival exists among prostate cancer (PCa) patients treated with ADT. Germ-line SNPs affecting function of genes critical to hormone synthesis, transport, metabolism, binding sites, and degradation may contribute to variability in clinical outcomes observed in PCa patients treated with ADT. Methods: Between 1/07 and 10/08, all PCa patients seen in the Indiana University Simon Cancer Center oncology clinics were approached for recruitment to the Prostate Cancer Genetic Risk Evaluation of SNPs Study (PROGRESS). Participants completed a demographic and clinical questionnaire and provided a peripheral blood sample. Only patients with confirmed ADT initiation dates were included in this analysis. Germ-line DNA was analyzed for SNP genotyping on a 128-SNP chip using a TaqMan OpenArray GT Kit (Applied Biosystems). The chip included genes critical to hormone signaling, transport, and elimination pathways with minor allele frequencies > 5%. Patients were followed for progression-free survival (PFS) and overall survival (OS) endpoints. Univariable analyses were performed to identify significant associations between SNP genotype, clinical parameters, and PFS and OS outcomes. Results: 107 patients with PCa initiated on ADT enrolled. Demographics included: age (median)–69 yrs, prostate specific antigen (PSA) (median)–28.0 ng/ml, PSA doubling time (median)–4.9 months, biochemical/metastatic–25%/75%, concurrent anti-androgen therapy–44%. No clinical parameters were associated with PFS and OS. Significant SNP associations with PFS and OS are summarized in the Table. Conclusions: Interpatient differences in hormone pathway germ-line SNPs may contribute to variability in clinical outcomes in patients treated with ADT. [Table: see text] [Table: see text]

Androgen pathway constitutional polymorphism predictors of progression-free and overall survivals in advanced castrate-resistant prostate cancer (CRPC) patients treated with ketoconazole (KC).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 54-54
Author(s):  
T. L. Davis ◽  
J. Jung ◽  
K. A. Carr ◽  
S. Philips ◽  
Y. Mohammadi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Indiana University ◽  
Hormone Synthesis ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Hormonal Therapies ◽  
Ecog Ps

54 Background: Recent trials have highlighted the clinical utility of second-line hormonal therapies for CRPC. KC, an oral inhibitor of CYP3A4 and CYP17, is commonly used in this setting. Germline SNPs in genes critical to hormone synthesis, transport, metabolism, binding sites, and degradation may contribute to variability in outcomes observed in KC treated CRPC pts. Methods: Between 1/07 and 10/08, all PCa pts seen in the Indiana University Simon Cancer Center oncology clinics were approached for recruitment to the Prostate Cancer Genetic Risk Evaluation of SNPs Study (PROGRESS). Participants completed a demographic and clinical questionnaire and provided a peripheral blood sample. Only pts with initiated on KC were included in this analysis. Germline DNA was analyzed for SNP genotyping on a 128-SNP chip using a TaqMan OpenArray GT Kit. The chip included genes critical to hormone signaling, transport, and elimination pathways with minor allele frequencies > 5%. Pts were followed for progression-free survival (PFS) and overall survival (OS) endpoints. Univariable analyses were performed to identify significant associations between SNP genotype, clinical parameters, and PFS and OS outcomes. Results: Between January 2007 and October 2008, 39 pts with CRPC initiated on KC therapy enrolled. Demographics included: age (median) – 70 yrs, prostate specific antigen (PSA) (median) – 13.0 ng/ml, PSA doubling time (median) – 2.9 months, metastatic –85%, ECOG PS 0– 74%. Age < 70 was associated with shorter PFS (p=0.010) and age > 70 was associated with shorter OS (p=0.030). SNPs significantly associated with PFS and OS are summarized in the table. Conclusions: Interpatient differences in hormonal pathway germline SNPs may contribute to variability in clinical outcomes in pts treated with KC. [Table: see text] No significant financial relationships to disclose.

Comparison of survival of African-American (AA) patients (pts) in docetaxel (D)-based combination therapies in metastatic castrate-resistant prostate cancer (mCRPC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 272-272
Author(s):  
Fatima Karzai ◽  
Ravi Amrit Madan ◽  
Yang-Min Ning ◽  
Marc Robert Theoret ◽  
Philip M. Arlen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Median Number ◽  
Incidence And Mortality ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Number Of Cycles ◽  
Ecog Ps

272 Background: AA pts experience greater prostate cancer (PC) incidence and mortality compared to Caucasian (C) pts but are underrepresented in clinical trials (CTs). Greater representation of AAs is required to explore differences in clinical benefit in advanced disease where recent data has reaffirmed the role of D. Methods: In a retrospective analysis, baseline characteristics, Gleason score (GS), ECOG PS, number of cycles (cys), maximum prostate-specific antigen (PSA) declines, radiographic responses, overall survival (OS) and progression-free survival (PFS) were captured in 2 recent D based CTs. Results: Of 136 pts, 28 (21%) self-identified as Black or AA. Median age of AA pts is 66 (50-78 yrs). Median GS is 8 (5-10). Median ECOG PS is 1 (0-2). 15 pts have bone and soft tissue disease; 13 pts have bone only disease. Median number of cys is 28.5 (1-63). Of 27 evaluable pts, 26 had PSA declines (-26 to -99%). Radiographic responses include 11 (39%) partial responses and 16 (57%) pts with stable disease. Median OS for AAs is 29.0 months (mos) (95% CI: 20.9-34.7 mos); median PFS is 21.5 mos (95% CI: 13.7-28.9 mos). Median OS for all non-AA pts is 24.8 mos (95% CI: 21.8-29.5 mos); median PFS is 16.1 mos (95% CI: 14.1-20.1 mos). The VEGF-634G > C SNP, associated with a more aggressive phenotype of PC, was evaluated in 54 pts. No evidence was found that genotype frequency varies between C and AA pts. Conclusions: In this analysis, AA pts did not have inferior OS (29 mos) or PFS (21.5 mos) outcomes compared to non-AA pts (24.8, 16.1 mos). Further analysis from larger studies is required to determine differential benefits of D for AA pts compared to non-AA pts. Clinical trial information: NCT00089609, NCT00942578.

Use of low-dose, weekly carboplatin in men with metastatic castrate-resistant prostate cancer (mCRPC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 331-331 ◽  
Author(s):  
Meghan O'Leary-Kelly ◽  
Dexiang Gao ◽  
Sarah Weisdack ◽  
Elaine Tat Lam ◽  
Brandon David Bernard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Low Dose ◽  
Treatment Options ◽  
Specific Antigen ◽  
Median Number ◽  
Prior Therapy ◽  
New Treatment ◽  
Castrate Resistant ◽  
Number Of Treatment

331 Background: Medical treatment options for advanced prostate cancer have evolved rapidly in recent years, with multiple new agents available. Our group had previously reported the use of weekly carboplatin for mCRPC in the pre-docetaxel era. The efficacy and toxicities of low-dose, weekly carboplatin were evaluated in a more contemporary patient cohort. Methods: We performed a retrospective review of patients with mCRPC treated with carboplatin from 2006-17 at a single health system. Carboplatin (AUC 2) was given weekly for 4 weeks of a 6-week cycle in combination with 1mg daily dexamethasone. Results: Sixty-four carboplatin-treated patients were identified, with a mean baseline prostate-specific antigen (PSA) of 568.55 ng/mL (range 0.02-4322). The median number of treatment cycles was 3 (range 1-10). The therapy was generally well tolerated and a dose-reduction was required for only 4 patients. Previous therapy included: docetaxel 95.3%, cabazitaxel 21.9%, abiraterone 53.1%, and enzalutamide 29.7%. A PSA decline of 30% occurred in 20 of 64 patients (31%). The response rate varied based on prior therapy. The most common adverse events were fatigue (80%), anemia (64%), and neuropathy (48%). There were 20 patients with Grade 3 adverse events. The most common was thrombocytopenia (n = 9), and 1 grade 4 thrombocytopenia. No other grade 4 toxicities were noted. Conclusions: New treatment options are needed for mCRPC after progression on currently approved agents. Platinum therapy may have increased activity in specific genomic subtypes of prostate cancer. These results compare favorably with the TROPC study of cabazitaxel (39% PSA response) in spite of the heavy pretreatment of our population. This retrospective report shows that carboplatin has activity and little toxicity in an unselected cohort of mCRPC.

scholarly journals Risk Prediction of Prostate Cancer with Single Nucleotide Polymorphisms and Prostate Specific Antigen

2019 ◽  
Vol 201 (3) ◽  
pp. 486-495 ◽  
Author(s):  
Sam Li-Sheng Chen ◽  
Jean Ching-Yuan Fann ◽  
Csilla Sipeky ◽  
Teng-Kai Yang ◽  
Sherry Yueh-Hsia Chiu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Prostate Specific Antigen ◽  
Risk Prediction ◽  
Specific Antigen ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Prostate-specific antigen as a measure of disease outcome in metastatic hormone-refractory prostate cancer.

1993 ◽  
Vol 11 (4) ◽  
pp. 607-615 ◽  
Author(s):  
W K Kelly ◽  
H I Scher ◽  
M Mazumdar ◽  
V Vlamis ◽  
M Schwartz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Specific Antigen ◽  
Phase Iii ◽  
Cancer Center ◽  
Hormone Refractory Prostate Cancer ◽  
Data Set ◽  
Hormone Refractory

PURPOSE To evaluate the prognostic significance of pretreatment parameters and posttherapy declines in prostate-specific antigen (PSA) in relation to the survival of patients with hormone-refractory prostate cancer. PATIENTS AND METHODS One hundred ten assessable patients treated on seven sequential protocols at Memorial Sloan-Kettering Cancer Center (MSKCC) for hormone-refractory prostate cancer were evaluated for 29 different pretherapy and posttherapy parameters, including a posttherapy decline in PSA of 50% and 80% from baseline. RESULTS In the univariate analysis, initial Karnofsky performance status (KPS) > or = 80% was associated with a favorable outcome (P = .005), while age, extent of disease on bone scan, and individual sites of metastatic disease were not significant. No difference in survival was observed between patients with measurable or assessable (bone only) disease. Initial hemoglobin (HGB; P = .0012), alkaline phosphatase (ALK; P = .0015), and lactate dehydrogenase (LDH; P = .0002) levels were significant discriminators, while the initial PSA was not. Using a landmark analysis, a significantly longer median survival rate was observed for patients with a > or = 50% decline in PSA (median not reached) versus patients with a less than 50% decline in PSA (median, 8.6 months; P = .0001). Multivariate analysis using the Cox proportional hazards model showed that a > or = 50% decline in PSA (P = .0004) and the natural log of LDH (P = .0001) were the two most significant variables predicting survival. The model was confirmed on an independent data set from the Norwegian Radium Hospital (NRH) in Oslo, Norway. CONCLUSION The results suggest that posttherapy PSA declines can be used as a surrogate end point to evaluate new agents in hormone-refractory prostate cancer. The criteria for response need prospective validation in phase III trials.

Germline pathologic mutations and cancer family history in prostate cancer patients.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 378-378
Author(s):  
Marcus Marie Moses ◽  
Elisa Ledet ◽  
Emma M. Ernst ◽  
Patrick Cotogno ◽  
Joshua Schiff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
San Francisco ◽  
Treatment Options ◽  
Distant Metastases ◽  
Cancer Center ◽  
Chi Square ◽  
Variant Of Uncertain Significance ◽  
Pathogenic Variants ◽  
Uncertain Significance

378 Background: Prostate cancer (PCa) patients (pts) with metastases and/or strong family history (FH) of cancer (Ca) are at higher risk of a germline mutation. The identification of alterations in PCa pts may be important for risk stratification as well as personalizing treatment options. The goal of this study was characterization of FH and pathogenic variants (PV) detected in PCa pts, with both localized and metastatic disease. Methods: 300 PCa pts from Tulane Cancer Center underwent germline testing. 265 Caucasian (C) and 35 African-Americans (AA) were tested and met the NCCN criteria for testing and/or had distant metastases (mets). Germline genetic testing was done via commercial panels (30-80 genes) (Invitae. San Francisco, Ca). PCa pts had extensive FH screening. Clinical annotation included age at diagnosis (dx), race, and presence of mets at any time. Chi square tests were used to compare clinical correlates and PVs. Results: Of the 300 pts tested, 182 pts (60.6%) had mets and 118 (39.4%) did not. 41 pts (13.6%) had ≥ 1 germline pathogenic variant (PV) and 161 pts (53.6%) had ≥ 1 germline variant of uncertain significance (VUS). PVs were detected in BRCA2 (n = 10), MUTYH (n = 8), CHEK2 (n = 6), BRCA1 (n = 4), ATM (n = 4), TP53 (n = 3), PMS2 (n = 2), BLM (n = 2), MITF (n = 2), NBN (n = 1), and RAD51D (n = 1). MUTYH and MITF are not known to be linked to prostate cancer. There was no significant relationships in FH PCa and FH non-PCa in regard to likelihood of a PV (p = .86 and p = .18). Of the 300 pts tested, 136 pts (45.3%) had PCa FH, 131 pts (43.6%) had breast Ca FH, 61 pts (20.3%) had lung Ca FH, 61 pts (20.3%) had colon Ca FH, 37 pts (12.3%) had pancreatic Ca FH, and 32 pts (10.6%) had ovarian Ca FH. 45.6% of C men (n = 121) and 42.8% of AA men (n = 15) had PCa FH. Pts with a non-PCa FH (n = 255) were 1.37 times more likely to develop mets (p = .01168). The median age of dx were 61 for PV pts, 62 for VUS pts, and 61 for negative pts (non-significant). 21/182 pts with mets (11.5%) had a PV; 8/182 (4.4%) pts with mets had a BRCA2 PV. Conclusions: In metastatic patients, FH of prostate cancer alone cannot predict those with PV. The most common Cas observed in these pts were breast, lung, colon and pancreatic. A larger cohort is needed to fully characterize and understand the co-segregation of PCa with other Cas.

Advancing age and the risk of adverse pathology at radical prostatectomy in men with biopsy Gleason score 6 prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 289-289
Author(s):  
Daniel Kim ◽  
Ming-Hui Chen ◽  
Hartwig Huland ◽  
Markus Graefen ◽  
Derya Tilki ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Specific Antigen ◽  
Cancer Center ◽  
Study Cohort ◽  
Pathologic Features ◽  
Younger Men ◽  
Biopsy Gleason Score ◽  
The Impact

289 Background: We evaluated the impact of age > 65 years versus younger on the odds of finding adverse pathologic features (pT3/T4 and/or R1 and/or Gleason score 8, 9, 10) at radical prostatectomy (RP) among men with biopsy Gleason score 6 prostate cancer (PC). Methods: The study cohort comprised 3191 men with biopsy Gleason score 6 PC treated with a RP between February 28, 1992 and February 15, 2016 at the Martini-Klinik Prostate Cancer Center. Multivariable logistic regression was used to evaluate the impact of age > 65 years versus younger on the adjusted odds ratio (AOR) of finding adverse pathology at RP adjusting for pre-RP prostate specific antigen (PSA), clinical tumor category, year of diagnosis, percent positive biopsies (PPB), and PSA density (PSAd). Results: Men age > 65 years as compared to younger had significantly lower median PPB (16.67% vs 20.0%; p = 0.01) and PSAd (0.13 ng/mL vs 0.15 ng/mL; p < 0.0001). Yet, while both increasing PPB (AOR 1.018, 95% CI 1.013, 1.023; p- < 0.0001) and PSAd (AOR 4.28, 95% CI 1.66, 11.01; p = 0.003) were significantly associated with an increased odds of finding adverse pathology at RP, men age > 65 years versus younger had a higher odds of adverse pathology at RP (AOR 1.28, 95% CI 1.002, 1.62; p = 0.048). Conclusions: Despite a more favorable median PPB and PSAd, men with biopsy Gleason score 6 PC and who are age > 65 years compared to younger men are at higher risk for having adverse pathology at RP and may benefit from a multiparametric MRI and targeted biopsy before proceeding with active surveillance. If higher grade/stage disease is discovered and treatment indicated then this information could guide both the use and duration of supplemental androgen deprivation therapy in men considering radiation therapy.

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