8 resultados para PSA

em Deakin Research Online - Australia


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Background Androgen-deprivation therapy is offered to men with prostate cancer who have a rising prostate-specific antigen after curative therapy (PSA relapse) or who are considered not suitable for curative treatment; however, the optimal timing for its introduction is uncertain. We aimed to assess whether immediate androgen-deprivation therapy improves overall survival compared with delayed therapy. Methods In this randomised, multicentre, phase 3, non-blinded trial, we recruited men through 29 oncology centres in Australia, New Zealand, and Canada. Men with prostate cancer were eligible if they had a PSA relapse after previous attempted curative therapy (radiotherapy or surgery, with or without postoperative radiotherapy) or if they were not considered suitable for curative treatment (because of age, comorbidity, or locally advanced disease). We used a database-embedded, dynamically balanced, randomisation algorithm, coordinated by the Cancer Council Victoria, to randomly assign participants (1:1) to immediate androgen-deprivation therapy (immediate therapy arm) or to delayed androgen-deprivation therapy (delayed therapy arm) with a recommended interval of at least 2 years unless clinically contraindicated. Randomisation for participants with PSA relapse was stratified by type of previous therapy, relapse-free interval, and PSA doubling time; randomisation for those with non-curative disease was stratified by metastatic status; and randomisation in both groups was stratified by planned treatment schedule (continuous or intermittent) and treatment centre. Clinicians could prescribe any form and schedule of androgen-deprivation therapy and group assignment was not masked. The primary outcome was overall survival in the intention-to-treat population. The trial closed to accrual in 2012 after review by the independent data monitoring committee, but data collection continued for 18 months until Feb 26, 2014. It is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12606000301561) and ClinicalTrials.gov (NCT00110162). Findings Between Sept 3, 2004, and July 13, 2012, we recruited 293 men (261 with PSA relapse and 32 with non-curable disease). We randomly assigned 142 men to the immediate therapy arm and 151 to the delayed therapy arm. Median follow-up was 5 years (IQR 3·3–6·2) from the date of randomisation. 16 (11%) men died in the immediate therapy arm and 30 (20%) died in the delayed therapy arm. 5-year overall survival was 86·4% (95% CI 78·5–91·5) in the delayed therapy arm versus 91·2% (84·2–95·2) in the immediate therapy arm (log-rank p=0·047). After Cox regression, the unadjusted HR for overall survival for immediate versus delayed arm assignment was 0·55 (95% CI 0·30–1·00; p=0·050). 23 patients had grade 3 treatment-related adverse events. 105 (36%) men had adverse events requiring hospital admission; none of these events were attributable to treatment or differed between treatment-timing groups. The most common serious adverse events were cardiovascular, which occurred in nine (6%) patients in the delayed therapy arm and 13 (9%) in the immediate therapy arm. Interpretation Immediate receipt of androgen-deprivation therapy significantly improved overall survival compared with delayed intervention in men with PSA-relapsed or non-curable prostate cancer. The results provide benchmark evidence of survival rates and morbidity to discuss with men when considering their treatment options. Funding Australian National Health and Medical Research Council and Cancer Councils, The Royal Australian and New Zealand College of Radiologists, Mayne Pharma Australia.

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Background: Debate about testing for prostate cancer using prostate-specific antigen (PSA) and digital rectal examination (DRE) continues. The evidence of benefit from screening for prostate cancer using PSA tests is inconclusive, and it is unclear how PSA can be used most effectively in the detection of prostate cancer. Given the lack of consensus, it is important that consumers understand the issues in a way that will permit them to decide whether or not to have a test and, if symptomatic, how their condition is managed.

Aims: To compare prostate cancer knowledge, attitudes and testing experiences reported by male doctors and men in the community, despite the lack of evidence of a benefit.

Methods : The primary method for ascertaining the attitudes of male doctors (MD) was a telephone survey, with some doctors electing to complete a written survey. Each MD was selected, at random, from a register of male practitioners aged ≥ 49 years of age. A total of 266 MD participated in the survey. The community sample (CS) was accessed using a telephone survey. Five hundred male Victorian residents aged ≥ 49 years of age participated in the study.

Results:
Knowledge − Overall, 55% of the CS indicated ­correctly that prostate disease is sometimes cancer, compared to 83% of MD.

Attitudes − Fifty-five per cent of MD believed men should be tested for prostate disease at least every 2 years, compared to 68% of men in the CS.

Testing experience − Forty-five per cent of MD had been tested for prostate cancer in the past, and 92% of those tests were reported as negative. In the CS, 56% had been tested for prostate cancer in the past, and 78% of the results were reported as negative. The ­significant independent predictors of having had a prostate test among MD were: (i) age (≥ 60 years; odds ratio (OR): 1.59; 95% confidence intervals (CI): 1.30−1.88) and (ii) positive attitudes towards regular testing for prostate cancer (OR: 2.27; 95% CI: 1.98−2.56). The significant independent predictors for the CS were: (i) age (≥ 60 years; OR: 1.65; 95% CI: 1.40−1.89), (ii) being married (OR: 1.30; 95% CI: 1.00−1.60), (iii) knowledge that prostate disease was sometimes cancer (OR: 1.46; 95% CI: 1.26−1.66) and (iv) positive attitudes towards regular testing for prostate cancer (OR: 2.12; 95% CI: 1.90−2.34).

Conclusions: The results highlight that testing for prostate cancer is widespread in the community and in the medical profession. Further research should be undertaken to identify how to help men make fully informed decisions about prostate cancer testing.

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OBJECTIVE: We conducted a case-control study of prostate cancer and familial risk of the disease in Australia between 1994 and 1998, a period during which the incidence of prostate cancer increased dramatically with widespread use of prostate-specific antigen (PSA) testing. METHODS: 1475 cases and 1405 controls were asked about prostate cancer in their first-degree relatives. Odds ratios (OR) were calculated using logistic regression. RESULTS: Cases were more likely to report a family history of prostate cancer than controls (OR 3.0; 95% confidence interval (CI) 2.3-3.9) and cases reporting an affected relative were younger (58.8 versus 60.9 years, p < 0.0001). The OR for an affected first-degree relative increased with increasing number of affected relatives and decreased with increasing age of the case. The OR for more than one affected first-degree relative was 6.9 (95% CI 2.7-18). The OR for an affected brother was 3.9 (95% CI 2.5-6.1) and for an affected father was 2.9 (95% CI 2.1-3.9) but these were not significantly different (p = 0.2). When analyses were repeated including only diagnoses made in relatives prior to 1992, the risks were generally similar except that the OR for an affected brother decreased to 3.1 (95% CI 1.2-3.9). When only relatives' diagnoses made after 1991 were included results were again similar to those for all relatives, although the effect for brothers was greater and the attenuation with age at diagnosis dissipated. CONCLUSIONS: The recent introduction of PSA testing that has resulted in a greater prevalence of apparent prostate cancer, does not appear to have substantially altered familial risks of disease, although effects associated with brothers may be inflated.

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In this work, an atmospheric pressure glow discharge helium plasma treatment was employed to modify the surface properties of jute fibres. The resulting bio-composites showed an increase in flexural properties and interlaminar shear strength (ILSS) compared to composites produced using untreated jute fibres. To understand the reason behind the ILSS improvement, the acid–base properties of jute fibres were determined by contact angle analysis using the capillary rise method. The results were fitted further to van Oss–Chaudhury–Good (vOCG) and Chang–Qin–Chen (CQC) models to determine the Lifshitz–van der Waals (LW) and acid–base components of surface energy. Surface energy determined by the vOCG model revealed that plasma treatment of jute fibre resulted in a 22% increase in total surface energy, a 19% increase in the LW component and a 24% increase in the acid–base component of surface energy. The increase in the acid–base component is due to the significant increase (69%) in the electron-accepting (γ+S) parameter. On the other hand, the CQC model clearly indicates an amphoteric nature of the fibre surface based on opposite signs of the acid and base principal values (PSa and PSb). Overall, the results indicated that increases in both LW and acid–base components were responsible for improvement in the properties of the composites.

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Background: Docetaxel (Taxotere) improve survival and prostate-specific antigen (PSA) response rates in patients with metastatic castrate-resistant prostate cancer (CRPC). We studied the combination of PI-88, an inhibitor of angiogenesis and heparanase activity, and docetaxel in chemotherapy-naive CRPC.

Patients and methods: We conducted a multicentre open-label phase I/II trial of PI-88 in combination with docetaxel. The primary end point was PSA response. Secondary end points included toxicity, radiologic response and overall survival. Doses of PI-88 were escalated to the maximum tolerated dose; whereas docetaxel was given at a fixed 75 mg/m2 dose every three weeks

Results: Twenty-one patients were enrolled in the dose-escalation component. A further 35 patients were randomly allocated to the study to evaluate the two schedules in phase II trial. The trial was stopped early by the Safety Data Review Board due to a higher-than-expected febrile neutropenia of 27%. In the pooled population, the PSA response (50% reduction) was 70%, median survival was 61 weeks (6–99 weeks) and 1-year survival was 71%.

Conclusions: The regimen of docetaxel and PI-88 is active in CRPC but associated with significant haematologic toxicity. Further evaluation of different scheduling and dosing of PI-88 and docetaxel may be warranted to optimise efficacy with a more manageable safety profile.

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Background Cabazitaxel, abiraterone, and enzalutamide are survival-prolonging treatments in men with castration-resistant prostate cancer (CRPC) progressing following docetaxel chemotherapy. The sequential activity of these agents has not been studied and treatment sequencing remains a key dilemma for clinicians. Objective To describe the antitumour activity of cabazitaxel after docetaxel and next-generation endocrine agents. Design, setting, and participants We report on a cohort of 59 men with progressing CRPC treated with cabazitaxel, 37 of whom had received prior abiraterone and 9 of whom had received prior enzalutamide. Outcome measurements and statistical analysis Changes in prostate-specific antigen (PSA) level were used to determine activity on abiraterone, enzalutamide, and cabazitaxel treatment. Radiologic tumour regressions according to Response Evaluation Criteria in Solid Tumors (RECIST) and symptomatic benefit were evaluated for cabazitaxel therapy. Results and limitations The post-endocrine-therapy patients received abiraterone (n = 32), sequential abiraterone and enzalutamide (n = 5) or enzalutamide (n = 4). These patients received a median of 7 mo of abiraterone and 11 mo of enzalutamide. A median of six cabazitaxel cycles (range: 1-10 cycles) were delivered, with ≥50% PSA declines in 16 of 41 (39%) patients, soft tissue radiologic responses in 3 of 22 (14%) evaluable patients, and symptomatic benefit in 9 of 37 evaluable patients (24%). Median overall survival and progression-free survival were 15.8 and 4.6 mo, respectively. Antitumor activity on cabazitaxel was less favourable in the abiraterone- and enzalutamide-naïve cohort (n = 18), likely reflecting biologic differences in this cohort. These data were obtained from a retrospective analysis. Conclusions This is the first report of cabazitaxel activity in CRPC progressing after treatment with docetaxel and abiraterone or enzalutamide. We demonstrate significant cabazitaxel activity in this setting. Patient summary We looked at the antitumour activity of the chemotherapy drug cabazitaxel in men previously treated with docetaxel chemotherapy and the hormonal drugs abiraterone and enzalutamide. Cabazitaxel appeared active when given after abiraterone and enzalutamide. We can reassure men that cabazitaxel can be used after these novel endocrine treatments. © 2013 European Association of Urology.

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Prostate cancer is one of the most diagnosed cancers which leads to a considerable number of deaths due to the lack of early and sensitive detection. This paper presents an aptamer functionalized field effect (FET) based biosensor for the detection of prostate cancer. Prostate specific antigen (PSA) is considered as the biomarker for prostate cancer whose detection is confirmed by attaching aptamers onto the sensor surface. Through the modelling and numerical simulation, the paper aims to evaluate and predict the performance parameters such as sensitivity, settling time, and limit of detection (LOD) of a label-free FET based electronic biosensor. Various sensor parameters such as structure (i.e., geometry), type of the FET (e.g., nanowire FET, spherical FET, ion-selective FET, and magnetic particle) radius of the FET channel and incubation time are optimized and analyzed. In addition, concentration of analyte biomolecules, diffusion coefficients and affinity to the receptor molecules are also investigated to determine the optimize performance parameters.