共查询到9条相似文献，搜索用时 0 毫秒
1.
Russell Szmulewitz Supriya MohileEdwin Posadas Rangesh KunnavakkamTheodore Karrison Elizabeth ManchenWalter M. Stadler 《European urology》2009
Background
Even in castration-resistant prostate cancer (CRPC), the androgen pathway remains biologically relevant. In preclinical models, androgen therapy for CRPC leads to growth arrest, apoptosis, and tumor shrinkage.Objective
This study sought to determine the toxicity and feasibility of a testosterone therapy in early CRPC.Design, setting, and participants
Prostate cancer patients with progressive disease following androgen ablation, antiandrogen therapy, and withdrawal and no to minimal metastatic disease who were followed at the University of Chicago were randomized to treatment with three doses of transdermal testosterone.Intervention
Patients were treated with transdermal testosterone at 2.5, 5.0, or 7.5 mg/day.Measurements
Toxicity, prostate-specific antigen (PSA), imaging, quality of life (QoL), and strength were monitored. Treatment was discontinued for significant toxicity, clinical progression, or a 3-fold increase in PSA.Results and limitations
Fifteen men with a median age of 73 yr (range: 62–92) and a median PSA of 11.1 ng/ml (range: 5.2–63.6) were treated. Testosterone increased from castrate to median concentrations of 305 ng/dl, 308 ng/dl, and 297 ng/dl for dosages of 2.5 mg/day (n = 4), 5.0 mg/day (n = 5), and 7.5 mg/day (n = 5), respectively. One patient was taken off of the study at 53 wk due to grade 4 cardiac toxicity. There were no other grade 3 or 4 toxicities related to the study medication, and the grade 2 toxicities were minimal. Only one patient experienced symptomatic progression, and three (20%) patients demonstrated a decrease in PSA (largest was 43%). Median time to progression was 9 wk (range: 2–96), with no detectable difference in the three dose cohorts. There was no significant improvement in QoL, and there was a borderline statistically significant improvement in hand-grip strength with treatment. The study was limited by sample size, single arm, and variability of baseline patient characteristics.Conclusions
Testosterone is a feasible and reasonably well-tolerated therapy for men with early CRPC. A larger, randomized trial is under way to further characterize efficacy and impact on QoL measures. 相似文献2.
Christopher C. Parker Robert E. Coleman Oliver Sartor Nicholas J. Vogelzang David Bottomley Daniel Heinrich Svein I. Helle Joe M. O&#x;Sullivan Sophie D. Foss? Ale? Chodacki Pawe? Wiechno John Logue Mihalj Seke Anders Widmark Dag Clement Johannessen Peter Hoskin Nicholas D. James Arne Solberg Sten Nilsson 《European urology》2018,73(3):427-435
3.
Michael J. Morris Daisy Huang William K. Kelly Susan F. Slovin Ryan D. Stephenson Caitlin Eicher Anthony Delacruz Tracy Curley Lawrence H. Schwartz Howard I. Scher 《European urology》2009
Background
Growth of selected castration-resistant prostate cancer (CRPC) cell lines and animal models can be repressed by reexposure to androgens. Low doses of androgens, however, can stimulate tumor growth.Objective
We performed a phase 1 clinical trial to determine the safety of high-dose exogenous testosterone in patients with castration-resistant metastatic prostate cancer (CRMPC).Design, setting, and participants
Patients with progressive CRMPC who had been castrate for at least 1 yr received three times the standard replacement dose of transdermal testosterone.Intervention
Cohorts of 3–6 patients received testosterone for 1 wk, 1 mo, or until disease progression.Measurements
Toxicities, androgen levels, prostate-specific antigen (PSA) assays, computed tomography (CT) scans, bone scintigraphy, positron emission tomography (PET) scans, and metastatic tumor biopsy androgen receptor levels were assessed.Results and limitations
Twelve patients were treated—three in cohorts 1 and 2 and six in cohort 3. No pain flares were noted. One patient came off study because of epidural disease, which was treated with radiation. Average testosterone levels were within normal limits, although dihydrotestosterone (DHT) levels on average were supraphysiologic in cohort 3. One patient achieved a PSA decline of >50% from baseline. No objective responses were seen. For cohort 3, median time on treatment was 84 d (range: 23–247 d).Conclusions
We have demonstrated that patients with CRMPC can be safely treated in clinical trials using high-dose exogenous testosterone. Patients did not, on average, achieve sustained supraphysiologic serum testosterone levels. Future studies should employ strategies to maximize testosterone serum levels, use contemporary methods of identifying patients with androgen receptor overexpression, and utilize PSA Working Group II Consensus Criteria clinical trial end points.Trial registration
ClinicalTrials.gov; NCT00006044. 相似文献4.
Andrew J. Vickers Tineke Wolters Caroline J. Savage Angel M. Cronin M. Frank O’Brien Kim Pettersson Monique J. Roobol Gunnar Aus Peter T. Scardino Jonas Hugosson Fritz H. Schröder Hans Lilja 《European urology》2009
Background
It has been suggested that changes in prostate-specific antigen (PSA) over time (ie, PSA velocity [PSAV]) aid prostate cancer detection. Some guidelines do incorporate PSAV cut points as an indication for biopsy.Objective
To evaluate whether PSAV enhances prediction of biopsy outcome in a large, representative, population-based cohort.Design, setting, and participants
There were 2742 screening-arm participants with PSA <3 ng/ml at initial screening in the European Randomized Study of Screening for Prostate Cancer in Rotterdam, Netherlands, or Göteborg, Sweden, and who were subsequently biopsied during rounds 2–6 due to elevated PSA.Measurements
Total, free, and intact PSA and human kallikrein 2 were measured for 1–6 screening rounds at intervals of 2 or 4 yr. We created logistic regression models to predict prostate cancer based on age and PSA, with or without free-to-total PSA ratio (%fPSA). PSAV was added to each model and any enhancement in predictive accuracy assessed by area under the curve (AUC).Results and limitations
PSAV led to small enhancements in predictive accuracy (AUC of 0.569 vs 0.531; 0.626 vs 0.609 if %fPSA was included), although not for high-grade disease. The enhancement depended on modeling a nonlinear relationship between PSAV and cancer. There was no benefit if we excluded men with higher velocities, which were associated with lower risk. These results apply to men in a screening program with elevated PSA; men with prior negative biopsy were not evaluated in this study.Conclusions
In men with PSA of about ≥3 ng/ml, we found little justification for formal calculation of PSAV or for use of PSAV cut points to determine biopsy. Informal assessment of PSAV will likely aid clinical judgment, such as a sudden rise in PSA suggesting prostatitis, which could be further evaluated before biopsy. 相似文献5.
Alberto Briganti Niccolò Passoni Matteo Ferrari Umberto Capitanio Nazareno Suardi Andrea Gallina Luigi Filippo Da Pozzo Maria Picchio Valerio Di Girolamo Andrea Salonia Liugi Gianolli Cristina Messa Patrizio Rigatti Francesco Montorsi 《European urology》2010
Background
Several guidelines have indicated that in patients with well-differentiated or moderately well-differentiated prostate cancer (PCa), a staging bone scan may be omitted. However, the guidelines recommendations have not yet been externally validated.Objective
The aim of the study was to externally validate the available guidelines regarding the need for a staging bone scan in patients with newly diagnosed PCa. Moreover, we developed a novel risk stratification tool aimed at improving the accuracy of these guidelines.Design, setting, and participants
The study included 853 consecutive patients diagnosed with PCa between January 2003 and June 2008 at a single centre. All patients underwent bone scan using technetium Tc 99m methylene diphosphonate at diagnosis.Measurements
The area under the curve (AUC) of the criteria suggested by the guidelines (European Association of Urology, American Urological Association, National Comprehensive Cancer Network, and American Joint Committee on Cancer) to perform a baseline bone scan was assessed and compared with the accuracy of a classification and regression tree (CART) including prostate-specific antigen (PSA), clinical stage, and biopsy Gleason sum as covariates.Results and limitations
The AUC of the guidelines ranged between 79.7% and 82.6%. However, the novel CART model, which stratified patients into low risk (biopsy Gleason ≤7, cT1–T3, and PSA <10 ng/ml), intermediate risk (biopsy Gleason ≤7, cT2/T3, and PSA >10 ng/ml), and high risk (biopsy Gleason >7) was significantly more accurate (AUC: 88.0%) than all the guidelines (all p ≤ 0.002). The limitation of this study resides in its retrospective design. Moreover, the proposed risk stratification tool can be considered only for patients who are candidates for radical prostatectomy until validated in other clinical settings.Conclusions
This is the first study aimed at externally validating the available guidelines addressing the need for staging baseline bone scans in PCa patients. All guidelines showed high accuracy. However, their accuracy was significantly lower compared with the accuracy of the novel risk stratification tool. According to this tool, staging bone scans might be considered only for patients with a biopsy Gleason score >7 or with a PSA >10 ng/ml and palpable disease (cT2/T3) prior to treatment. However, before recommending its use in clinical practice, our model needs to be externally validated. 相似文献6.
Nicholas D. James Armelle Caty Michael Borre Bernard A. Zonnenberg Philippe Beuzeboc Thomas Morris De Phung Nancy A. Dawson 《European urology》2009
Background
The endothelin-A receptor (ETAR) has been implicated in the progression of prostate cancer.Objectives
To investigate the safety and efficacy of the specific ETAR antagonist ZD4054 in patients with metastatic hormone-resistant prostate cancer (HRPC).Design, setting, and participants
Double-blind, placebo-controlled, randomised, parallel-group, multicentre, phase 2 trial in patients attending cancer centres with HRPC and bone metastases who were pain free or mildly symptomatic for pain.Intervention
Patients were randomised to receive once-daily oral tablets of ZD4054 10 mg, or ZD4054 15 mg, or placebo.Measurements
The primary end point was time to progression, defined as clinical progression, requirement for opiate analgesia, objective progression of soft-tissue metastases, or death in the absence of progression. Secondary end points included overall survival, time to prostate-specific antigen (PSA) progression, and safety. Statistical significance was preset at 20%.Results and limitations
A total of 312 patients were randomised (ZD4054 10 mg, n = 107; ZD4054 15 mg, n = 98; placebo, n = 107). At the primary analysis, median time to progression was 3.6 mo, 4.0 mo, and 3.8 mo in the placebo, ZD4054 10 mg, and ZD4054 15 mg groups, respectively, with no statistically significant difference between ZD4054 groups and placebo (hazard ratio [HR] vs placebo for the ZD4054 10 mg group: 0.88 [80% CI: 0.71–1.09]; HR vs placebo for the ZD4054 15 mg group: 0.83 [80% CI: 0.66–1.03]). However, a signal for prolonged overall survival was observed in the ZD4054 treatment groups versus placebo, based on 40 deaths. At a subsequent analysis after 118 deaths, this survival benefit was confirmed (HR vs placebo for the ZD4054 10 mg group, 0.55 [80% CI: 0.41–0.73], p = 0.008; HR vs placebo for the ZD4054 15 mg group, 0.65 [80% CI: 0.49–0.86], p = 0.052) but the differences in time to progression remained nonsignificant. Median overall survival was 17.3 mo, 24.5 mo, and 23.5 mo in the placebo group, the ZD4054 10 mg group, and the ZD4054 15 mg group, respectively. Discordance between results for time to progression and overall survival may be due to the sensitivity of the definition of progression. Adverse events were in line with the expected pharmacologic effects of an ETAR antagonist.Conclusions
The primary end point of time to progression was not achieved in this study, but an improvement was seen in overall survival in both active treatment arms. ZD4054 was well tolerated.Trial registration
Clinicaltrials.gov NCT00090363. 相似文献7.
Fritz H. Schröder Jonas Hugosson Sigrid Carlsson Teuvo Tammela Liisa Määttänen Anssi Auvinen Maciej Kwiatkowski Franz Recker Monique J. Roobol 《European urology》2012
Background
Metastatic disease is a major morbidity of prostate cancer (PCa). Its prevention is an important goal.Objective
To assess the effect of screening for PCa on the incidence of metastatic disease in a randomized trial.Design, setting, and participants
Data were available for 76 813 men aged 55–69 yr coming from four centers of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The presence of metastatic disease was evaluated by imaging or by prostate-specific antigen (PSA) values >100 ng/ml at diagnosis and during follow-up.Intervention
Regular screening based on serum PSA measurements was offered to 36 270 men randomized to the screening arm, while no screening was provided to the 40 543 men in the control arm.Outcome measurements and statistical analysis
The Nelson-Aalen technique and Poisson regression were used to calculate cumulative incidence and rate ratios of M+ disease.Results and limitations
After a median follow-up of 12 yr, 666 men with M+ PCa were detected, 256 in the screening arm and 410 in the control arm, resulting in cumulative incidence of 0.67% and 0.86% per 1000 men, respectively (p < 0.001). This finding translated into a relative reduction of 30% (hazard ratio [HR]: 0.70; 95% confidence interval [CI], 0.60–0.82; p = 0.001) in the intention-to-screen analysis and a 42% (p = 0.0001) reduction for men who were actually screened. An absolute risk reduction of metastatic disease of 3.1 per 1000 men randomized (0.31%) was found. A large discrepancy was seen when comparing the rates of M+ detected at diagnosis and all M+ cases that emerged during the total follow-up period, a 50% reduction (HR: 0.50; 95% CI, 0.41–0.62) versus the 30% reduction. The main limitation is incomplete explanation of the lack of an effect of screening during follow-up.Conclusions
PSA screening significantly reduces the risk of developing metastatic PCa. However, despite earlier diagnosis with screening, certain men still progress and develop metastases.The ERSPC trial is registered under number ISRCTN49127736. 相似文献8.
Philip Van Kerrebroeck François Haab Javier C. Angulo Viktor Vik Ferenc Katona Alberto Garcia-Hernandez Monique Klaver Klaudia Traudtner Matthias Oelke 《European urology》2013
Background
Storage symptoms are often undertreated in men with lower urinary tract symptoms (LUTS).Objective
To evaluate the combination of an antimuscarinic (solifenacin) with an α-blocker (tamsulosin) versus tamsulosin alone in the treatment of men with LUTS.Design, setting, and participants
A double-blind, 12-wk, phase 2 study in 937 men with LUTS (≥3 mo, total International Prostate Symptom Score [IPSS] ≥13, and maximum urinary flow rate 4.0–15.0 ml/s).Intervention
Eight treatment groups: tamsulosin oral controlled absorption system (OCAS) 0.4 mg; solifenacin 3, 6, or 9 mg; solifenacin 3, 6 or 9 mg plus tamsulosin OCAS 0.4 mg; or placebo.Outcome measurements and statistical analysis
The primary efficacy end point was change from baseline in total IPSS. Secondary end points included micturition diary and quality-of-life (QoL) parameters. Post hoc subgroup analyses were performed by severity of baseline storage symptoms, with statistical comparisons presented only for tamsulosin OCAS alone versus combination therapy, due to the small sample size of the solifenacin monotherapy and placebo subgroups.Results and limitations
Combination therapy was associated with significant improvements in micturition frequency and voided volume versus tamsulosin OCAS alone in the total study population; improvements in total IPSS were not significant. Statistically significant improvements in urgency episodes, micturition frequency, total urgency score, voided volume, IPSS storage subscore, IPSS-QoL index, and Patient Perception of Bladder Condition were observed in a subpopulation of men with two or more urgency episodes per 24 h (Patient Perception of Intensity of Urgency Scale grade 3 or 4) and eight or more micturitions per 24 h at baseline (storage symptoms subgroup) with combination therapy versus tamsulosin OCAS alone (p ≤ 0.05 for the dose–response slope, all variables). Combination therapy was well tolerated, and adverse events were consistent with the safety profiles of both compounds.Conclusions
Solifenacin plus tamsulosin OCAS did not significantly improve IPSS in the total study population but offered significant efficacy and QoL benefits over tamsulosin OCAS monotherapy in men with both voiding and storage symptoms at baseline. Combination therapy was well tolerated.ClinicalTrials.gov identifier
NCT00510406 相似文献9.
Maurizio Brausi Jorg Oddens Richard Sylvester Aldo Bono Cees van de Beek George van Andel Paolo Gontero Levent Turkeri Sandrine Marreaud Sandra Collette Willem Oosterlinck 《European urology》2014