Prognostic role of docetaxel-induced reduction of free testosterone serum levels in metastatic prostate cancer patients.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 144-144
Author(s):  
Paula Kappler ◽  
Stefan Brunotte ◽  
Philipp Ivanyi ◽  
Michael A. Morgan ◽  
Christoph W. Reuter
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Cox Regression ◽  
Specific Antigen ◽  
Serum Levels ◽  
Prognostic Role ◽  
Cycle Number ◽  
Prognostic Risk Factors ◽  
The Impact

144 Background: We have recently demonstrated that a salvage therapy with carboplatin plus weekly docetaxel is effective in docetaxel-refractory prostate cancer (PC) and interferes with testosterone biosynthesis (Reuter et al.; Oncol Res & Treat. 2018, 41 (suppl.1): p.10). In this study, the impact of docetaxel monotherapy on free and total testosterone serum levels (fT, TT) and the prognostic role of fT and TT were analyzed in mPC patients. Methods: 62 consecutive mPC patients were treated with at least two cycles of docetaxel (75 mg/m2 q3w; 50 mg/m2 q2w, or 35 mg/m2 q1w) until disease progression, occurrence of intolerable adverse effects or completion of the planned cycle number. Efficacy measures were done following PCWG2 recommendations. FT and TT were measured before and during chemotherapy. Results: At the current analysis (August 31, 2020), the median follow-up time was 21.2 months. Response of prostate-specific antigen (PSAR; ≥50% PSA reduction) was observed in 42/62 (67.7%) and 12/36 (33.3%) patients with measurable disease exhibited a partial remission (PR). Median progression-free survival (PFS) for all patients was 8.1 months (CI 95% 3.6, 12.5) and median overall survival (OS) was 25.7 months (CI 95% 19.4, 32.1). The most common reversible grade 3/4 toxicity was leukopenia/neutropenia (29/33.9%). Median fT and TT serum levels were reduced below the detection limit during docetaxel treatment (fT: from 0.34 pg/mL to < 0.01 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified PSAR > 50%, fT reduction of 100% and number of organs involved as independent prognostic risk factors for PFS. Furthermore, fT reduction of 100% and FT nadir values < 0.01 pg/mL were independent prognostic risk factors for OS (p < 0.05). Conclusions: These data demonstrate that fT is an important prognostic factor for PFS and OS in mPC patients.

scholarly journals Prognostic role of docetaxel-induced suppression of free testosterone serum levels in metastatic prostate cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paula Kappler ◽  
Michael A. Morgan ◽  
Philipp Ivanyi ◽  
Stefan J. Brunotte ◽  
Arnold Ganser ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Cox Regression ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Biologically Active ◽  
Free Form ◽  
Total Testosterone ◽  
The Impact

AbstractTo date, only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer (mPC) and the impact of FT on disease, therapy and outcome is largely unknown. We retrospectively studied the effect of docetaxel on FT and total testosterone (TT) serum levels in 67 mPC patients monitored between April 2008 and November 2020. FT and TT levels were measured before and weekly during therapy. The primary endpoint was overall survival (OS). Secondary endpoints were prostate-specific antigen response and radiographic response (PSAR, RR), progression-free survival (PFS), FT/TT levels and safety. Median FT and TT serum levels were completely suppressed to below the detection limit during docetaxel treatment (FT: from 0.32 to < 0.18 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified requirement of non-narcotics, PSAR, complete FT suppression and FT nadir values < 0.18 pg/mL as independent parameters for PFS. Prior androgen-receptor targeted therapy (ART), soft tissue metastasis and complete FT suppression were independent prognostic factors for OS. FT was not predictive for treatment outcome in mPC patients with a history of ART.

Role of free testosterone serum levels during salvage chemotherapy with carboplatin plus weekly docetaxel in patients with docetaxel-refractory, metastatic castration-resistant prostate cancer (mCRPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 145-145
Author(s):  
Stefan Brunotte ◽  
Philipp Ivanyi ◽  
Paula Kappler ◽  
Michael A. Morgan ◽  
Christoph W. Reuter
Keyword(s):  
Prostate Cancer ◽  
Detection Limit ◽  
Lung Metastases ◽  
Objective Response ◽  
Specific Antigen ◽  
Serum Levels ◽  
Total Testosterone ◽  
Castration Resistant Prostate Cancer ◽  
The Impact

145 Background: Carboplatin plus docetaxel (CD) may be effective in mDRPC. Platinum(II)-complexes interfere with steroid biosynthesis and thus lower testosterone levels . In this study, the impact of CD on free and total testosterone (fT, TT) serum levels and the prognostic role of fT and TT were analyzed in mDRPC patients. Methods: Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Treatment consisted of at least 2 cycles of carboplatin AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel (35 mg/m2) iv for one hour on days 1, 8, (15) plus prednisone 2x5 mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. Results: Of the 118 pts. treated since February 2005, 95.8% had bone, 47.5% lymph node, 28.0% liver and 20.3% lung metastases. Median follow-up time was 14.4 months at the time of the current analysis. The objective response rate (ORR) was 46.4% in the 69 pts. with measureable disease (58.5%). Response of prostate-specific antigen (PSAR ≥ 50%) was observed in 56 (47.9%) patients. Median progression free survival (PFS) was 7.6 months (CI 95% 6.0, 9.1) and median overall survival (OS) was 15.7 months (CI 95% 12.2, 19.2). The most common reversible grade 3/4 toxicity was leukopenia/ neutropenia (36.4/28.8%). Median FT serum levels were 0.35 pg/mL before and < 0.18 pg/mL during CD treatment (nadir levels, p < 0.001; detection limit < 0.18 pg/mL). In multivariate analyses, LDH > 2xULN, PSAR≥50% and FT nadir levels below the detection limit ( < 0.18 pg/mL) during CD treatment were associated with longer PFS (p < 0.05). Conclusions: These data suggest that CD may be an important salvage treatment option for mDRPC patients by inhibition of the testosterone biosynthesis.

Effectiveness of abiraterone as salvage therapy in patients with docetaxel- and castration-resistant prostate cancer (mDCPC) that progressed during second-line chemotherapy with carboplatin plus weekly docetaxel (DC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 162-162
Author(s):  
Christoph W. Reuter ◽  
Michael A. Morgan ◽  
Martin Fenner ◽  
Viktor Grünwald ◽  
Arnold Ganser
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Disease Progression ◽  
Salvage Therapy ◽  
Specific Antigen ◽  
Free Testosterone ◽  
Serum Levels ◽  
Castration Resistant Prostate Cancer ◽  
Psa Response ◽  
The Impact

162 Background: Our recent data have shown that carboplatin AUC5 on d1 plus docetaxel at a dose of 35 mg/m2 iv on d1, 8, 15 every 4 weeks (q4w) is an effective salvage therapy in mDRPC. Patients (pts) who have progressive disease during DC treatment survive only ~7 months and many are symptomatic. We have demonstrated that high free testosterone (FT) serum levels during DC treatment have a negative prognostic value for PSA response and overall survival in these pts. In this study the impact of abiraterone treatment and other subsequent salvage regimens after DC failure was analyzed. Methods: DC failure was defined as disease progression during DC treatment according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 74 consecutive DRPC pts were treated with at least 2 cycles DC until disease progression. At the time of the current analysis 67 pts have progressed and 41 pts received one or more subsequent therapies (1-3). Results: Overall survival (OS) of all 67 pts who have progressed during DC treatment was 7.1 months (CI 95% 1.8, 12.3). 41 pts received subsequent salvage therapies including mitoxantrone-prednisone-etoposide (MPE) (n=10), cabazitaxel (n=10), docetaxel-oxaliplatin (n=8), abiraterone (n=15) and doxorubicin-ketokonazol (n=5). OS of these 41 pts was 14.6 months (CI 95% 11.0, 18.3).In pts receiving abiraterone as salvage treatment, OS after DC was 21.8 months (CI 95% 7.2, 36.5) versus 11.9 months (CI 95% 9.0, 14.8) in pts receiving other regimens (HR 0.302, CI 95% 0.11, 0.8; p=0.016). Responses of prostate-specific antigen (PSAR; ≥30% and ≥50%) were only observed in pts receiving abiraterone (8/15, 53.3% and 4/15, 26.7%, respectively). Conclusions: Our data demonstrate for the first time that testosterone is an important prognostic factor for PSA response and OS in mDRPC patients receiving DC chemotherapy and that targeting testosterone after DC failure prolongs post-DC survival.

MYCN oncogene amplification in neuroblastoma is associated with worse prognosis, except in stage 4s: the Italian experience with 295 children.

1997 ◽  
Vol 15 (1) ◽  
pp. 85-93 ◽  
Author(s):  
G P Tonini ◽  
L Boni ◽  
A Pession ◽  
D Rogers ◽  
A Iolascon ◽  
...  
Keyword(s):  
Neuron Specific Enolase ◽  
Serum Levels ◽  
Prognostic Indicators ◽  
Mycn Amplification ◽  
Prognostic Role ◽  
Oncogene Amplification ◽  
Stage 1 ◽  
The Impact ◽  
Worse Prognosis

PURPOSE To evaluate the prognostic role of MYCN oncogene amplification in children with neuroblastoma. PATIENTS AND METHODS Of 694 children (age, 0 to 15 years) with previously untreated neuroblastoma, 295 (42%) were evaluated at diagnosis for MYCN gene amplification. RESULTS Clinical characteristics and survival results of 295 patients studied and 399 not studied for MYCN were comparable. In 48 of 295 patients studied for MYCN (16%), the gene was amplified (> or = three gene copies). Amplification was more frequent in children older than 1 year, with abdominal tumor (18% v 7%), advanced disease, normal vanillylmandelic (VMA) urinary excretion, and high lactate dehydrogenase (LDH), ferritin, and neuron-specific enolase (NSE) serum levels. In patients studied for MYCN, the 5-year overall survival (OS) rate was higher for children aged less than 1 year (90% v 44%), with extraabdominal tumor, stage 1 or 2 versus 3 versus 4, and normal NSE, LDH, and ferritin serum levels. Patients with amplified MYCN had a worse OS (odds ratio [OR], 3.38; confidence interval [CI], 2.22 to 5.16). This association held after adjustment for other characteristics. The impact of MYCN amplification was greater in patients with favorable characteristics, in particular age (OR, 10.28 for infants; 2.08 for older children) and stage (OR, 35.3 for stage 1 to 2; 8.41 for stage 3; 1.76 for stage 4). However, of 29 children with stage 4s, all three with amplified MYCN survive. In a multivariate analysis, the prognostic role of MYCN amplification, age, and stage was confirmed, but the size of the effect of MYCN was dependent on age and stage. CONCLUSION MYCN amplification is associated with a worse prognosis in children with neuroblastoma at all ages and stages except 4s. This association is most pronounced in children with otherwise favorable prognostic indicators, and in these children should be considered as an indication for more intensive intervention.

scholarly journals Prostate cancer biomarkers and multiparametric MRI: is there a role for both in prostate cancer management?

2021 ◽  
Vol 13 ◽  
pp. 175628722199718
Author(s):  
Anna Saltman ◽  
Joseph Zegar ◽  
Monzer Haj-Hamed ◽  
Sadhna Verma ◽  
Abhinav Sidana
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Prostate Imaging ◽  
Cancer Management ◽  
Screening And Surveillance ◽  
Prostate Health Index ◽  
Novel Biomarkers ◽  
Prostate Health ◽  
The Impact

Several advancements have been made in recent years with regards to the detection and evaluation of prostate cancer (PCa). The low specificity of prostate specific antigen (PSA) has left much to be desired in a test, but a boom in novel biomarkers has made screening and surveillance more complicated. Several attempts at identifying a niche for these tests has helped somewhat, but much is still undetermined about the benefit that each test provides. In addition to laboratory tests, advancements in multiparametric magnetic resonance imaging (mpMRI) and PIRADSv.2 scoring have provided significant benefit to the evaluation of PCa. With the widespread use of prostate imaging, it is important to re-evaluate the impact of novel biomarkers in the context of furthering PCa screening and management. In this review, we aim to assess the influence mpMRI has on the role of nine different novel biomarkers in the detection and evaluation of PCa. We performed a review of current peer-reviewed literature to assess this question. Much data has been published on the role of these tests, allowing for their placement into one of three best-fit categories: tests for biopsy-naïve men (Prostate Health Index, Mi Prostate Score, 4K Score); tests for men with prior negative biopsies (ConfirmMDx, Progensa PCA3); and men on active surveillance (OncotypeDx, Prolaris, Decipher). Data on the role of these tests with the use of mpMRI have not been comprehensive and excludes several of the markers. More research is needed to determine the combined impact mpMRI and the novel biomarkers on the evaluation and management of PCa.

A comparison of surrogate endpoints for all cause mortality in men with localized unfavorable-risk prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 21-21
Author(s):  
Trevor Joseph Royce ◽  
Ming-Hui Chen ◽  
Jing Wu ◽  
Marian Loffredo ◽  
Andrew A. Renshaw ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Specific Antigen ◽  
Study Cohort ◽  
Risk Of Death ◽  
Psa Failure ◽  
All Cause Mortality ◽  
Risk Prostate Cancer ◽  
Psa Nadir ◽  
The Impact

21 Background: Several surrogates for prostate cancer-specific mortality exist, but whether these are surrogates for all cause mortality (ACM), and how their performance compares, is unknown. We investigated the relative efficacy of 4 candidate surrogates for ACM using the proportion of treatment effect (PTE) metric. Methods: Two-hundred and six men with localized unfavorable-risk prostate cancer were randomized to radiation therapy (RT) or RT and 6 months of androgen-deprivation therapy (ADT) from 1995 to 2001 and followed for a median of 16.62 years. Among the 159 men with no or minimal comorbidity, a significant reduction in the risk of death was observed in those randomized to RT and ADT versus RT alone; these 159 men formed the study cohort. In order to assess whether the candidate surrogated satisfied Prentice’s criteria for surrogacy, Cox regression analyses were performed to assess the risk of death for each of the candidate surrogates and treatment before and after adjusting for prostate-specific antigen (PSA), age at randomization, T category, and Gleason score. Results: PSA nadir > 0.5 ng/mL, PSA doubling time < 9 months and interval to PSA failure < 30 months met Prentice’s criteria for surrogacy (P = 0.01, 0.003, and 0.03 for the surrogate covariate in the multivariable model, respectively) for ACM, while PSA failure did not (P = 0.10). For the three surrogates, the PTE values were 103.86%, 43.09%, and 41.26%, respectively. Conclusions: A PSA nadir value of > 0.5 ng/mL following RT and ADT identified men prior to PSA failure who were at high-risk for death and therefore could be used to select men for entry, at the time of PSA nadir and before PSA failure, onto randomized trials evaluating the impact on survival of salvage ADT with or without agents shown to prolong survival in men with castrate-resistant metastatic prostate cancer. By enriching study cohorts with men who have achieved a surrogate endpoint for ACM, one can enhance the likelihood that the study will be able to observe whether survival is prolonged when novel treatment is added to ADT, as compared to ADT alone, in an abbreviated time period. Clinical Trial Number: NCT00116220

scholarly journals Development of diabetes mellitus following hormone therapy in prostate cancer patients is associated with early progression to castration resistance

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomonori Hayashi ◽  
Tomoyoshi Miyamoto ◽  
Noriaki Nagai ◽  
Atsufumi Kawabata
Keyword(s):  
Prostate Cancer ◽  
Diabetes Mellitus ◽  
Risk Factors ◽  
Hormone Therapy ◽  
Univariate Analysis ◽  
Specific Antigen ◽  
Initial Diagnosis ◽  
Rank Test ◽  
Castration Resistance ◽  
The Impact

AbstractTo identify risk factors for the prognosis of prostate cancer (PC), we retrospectively analyzed the impact of lifestyle-related disorders as well as PC characteristics at initial diagnosis on the progression to castration-resistant PC (CRPC) in PC patients undergoing hormone therapy. Of 648 PC patients, 230 who underwent hormone therapy and met inclusion criteria were enrolled in this study. CRPC developed in 48 patients (20.9%). Univariate analysis using Cox proportional hazard model indicated that newly developed diabetes mellitus (DM) following hormone therapy (postDM), but not preexisting DM, as well as PC characteristics at initial diagnosis including prostate-specific antigen (PSA) ≥ 18 were significantly associated with the progression to CRPC. A similar tendency was also observed in the relationship between newly developed hypertension following hormone therapy and CRPC progression. On the other hand, neither dyslipidemia nor hyperuricemia, regardless the onset timing, exhibited any association with CRPC progression. In multivariate analysis, postDM and PSA ≥ 18 were extracted as independent risk factors for CRPC progression (adjusted hazard ratios, 3.38 and 2.34; p values, 0.016 and 0.019, respectively). Kaplan–Meier analysis and log-rank test clearly indicated earlier progression to CRPC in PC patients who developed postDM or had relatively advanced initial PC characteristics including PSA ≥ 18. Together, the development of lifestyle-related disorders, particularly DM, following hormone therapy, as well as advanced PC characteristics at initial diagnosis is considered to predict earlier progression to CRPC and poor prognosis in PC patients undergoing hormone therapy.

Effectiveness of abiraterone as salvage therapy in patients with docetaxel- and castration-resistant prostate cancer (mDCPC) that progressed during second-line chemotherapy with carboplatin plus weekly docetaxel (DC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16064-e16064
Author(s):  
Michael A. Morgan ◽  
Martin Fenner ◽  
Viktor Grünwald ◽  
Axel S. Merseburger ◽  
Arnold Ganser ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Disease Progression ◽  
Salvage Therapy ◽  
Specific Antigen ◽  
Free Testosterone ◽  
Serum Levels ◽  
Castration Resistant Prostate Cancer ◽  
Psa Response ◽  
The Impact

e16064 Background: Our recent data have shown that carboplatin AUC5 on d1 plus docetaxel at a dose of 35 mg/m2 iv on d1, 8, 15 every 4 weeks (q4w) is an effective salvage therapy in mDRPC. Patients (pts) who have progressive disease during DC treatment survive only ~7 months and many are symptomatic. We have demonstrated that high free testosterone (FT) serum levels during DC treatment have a negative prognostic value for PSA response and overall survival in these pts. In this study the impact of abiraterone treatment and other subsequent salvage regimens after DC failure was analyzed. Methods: DC failure was defined as disease progression during DC treatment according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 74 consecutive DRPC pts were treated with at least 2 cycles DC until disease progression. At the time of the current analysis 69 pts have progressed and 43 pts received one or more subsequent therapies (1-3). Results: Overall survival (OS) of all 69 pts who have progressed during DC treatment was 8.0 months (CI 95% 3.7, 12.3). 43 pts received subsequent salvage therapies including mitoxantrone-prednisone-etoposide (MPE) (n=10), cabazitaxel (n=13), docetaxel-oxaliplatin (n=8), abiraterone (n=15), enzalutamide (n=5) and doxorubicin-ketokonazol (n=5). OS of these 43 pts was 14.6 months (CI 95% 11.0, 18.2).In pts receiving abiraterone as salvage treatment, OS after DC was 21.8 months versus 11.9 months (CI 95% 9.0, 14.8) in pts receiving other regimens (HR 0.17, CI 95% 0.07, 0.42; p<0.001). Responses of prostate-specific antigen (PSAR; ≥30% and ≥50%) were only frequently observed in pts receiving abiraterone (8/15, 53.3% and 4/15, 26.7%, respectively). Conclusions: Our data demonstrate for the first time that testosterone is an important prognostic factor for PSA response and OS in mDRPC patients receiving DC chemotherapy and that targeting testosterone after DC failure prolongs post-DC survival.

Stress, Cortisol and Suicide Risk

2019 ◽  
Author(s):  
Daryl Brian O'Connor
Keyword(s):  
Risk Factors ◽  
Suicidal Behavior ◽  
Suicide Risk ◽  
Stressful Events ◽  
Additional Risk ◽  
Global Health Issue ◽  
History Of ◽  
Hpa Axis Activity ◽  
The Impact

Suicide is a global health issue accounting for at least 800,000 deaths per annum. Numerous models have been proposed that differ in their emphasis on the role of psychological, social, psychiatric and neurobiological factors in explaining suicide risk. Central to many models is a stress-diathesis component which states that suicidal behavior is the result of an interaction between acutely stressful events and a susceptibility to suicidal behavior (a diathesis). This article presents an overview of studies that demonstrate that stress and dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, are important additional risk factors for suicide. Evidence for other putative stress-related suicide risk factors including childhood trauma, impaired executive function, impulsivity and disrupted sleep are considered together with the impact of family history of suicide, perinatal and epigenetic influences on suicide risk.

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