Abstract:
OBJECTIVES:To determine the risk of failure during drug development in castration-resistant prostate cancer (CRPC) and to identify factors that could improve outcomes. METHODS:We investigated CRPC by analysing compounds in phase I to phase III clinical trials between 1998 and April 2011. Drug development failures were classified as medical or commercial and were compared with industry expectations. Compounds were excluded from analysis if their phase I occurred before 1998, if they targeted patients that were did not have hormone-refractory prostate cancer, or if they did not assess outcomes such as overall survival, time to disease progression, or prostate-specific antigen levels. RESULTS:Thorough searches of clinicaltrial.gov and other databases yielded 77 compounds that met the inclusion criteria. The cumulative pass rate for first-line compounds in CRPC was 3% and was far below aggregate industry expectations. In total, there were nearly equivalent numbers of commercial and medical failures. Biological products were found to have had greater relative success than small-molecule drugs and biotechnology firms had been slightly more successful than pharmaceutical firms in this disease indication. Phase III failures were high, despite equally high failures during phase II. CONCLUSIONS:Currently, one in 33 compounds that enters clinical testing will be awarded US Food and Drug Administration approval. This appears to be the highest risk indication investigated to date, based on clinical trial studies alone, with an average cost of $1.411bn to bring a new drug to market when adjusted for risk. Development of radical therapeutics such as immunotherapies may also be warranted instead of classic antineoplastic therapeutics. Given the high clinical trial risk, efforts may have to shift to biomarker and surrogate endpoints to manage future clinical trial risk in prostate cancer.
journal_name
BJU Intjournal_title
BJU internationalauthors
Tenuta A,Klotz L,Parker JLdoi
10.1111/bju.12309subject
Has Abstractpub_date
2014-05-01 00:00:00pages
E82-9issue
5beissn
1464-4096issn
1464-410Xjournal_volume
113pub_type
杂志文章abstract:OBJECTIVE:• To report outcomes for patients with localized prostate cancer managed using a watchful waiting strategy at an American centre and to explore factors that have triggered intervention. PATIENTS AND METHODS:• From 1991 to 2005, 218 patients diagnosed with untreated localized prostate cancer were followed at ...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2010.09652.x
更新日期:2011-05-01 00:00:00
abstract:OBJECTIVE:To evaluate the oncological outcome and functional results of prostate-sparing cystectomy (PSC), proposed for treating bladder cancer, used since 1999 in our institution in an attempt to preserve male sexuality and to increase continence after cystectomy. PATIENTS AND METHODS:Between January 1999 and Decembe...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2004.05097.x
更新日期:2004-11-01 00:00:00
abstract:OBJECTIVE:To investigate the immunology of host-tumour interaction, critical for the development of immunotherapy against cancers, by assessing the major histocompatibility complex (MHC) class I expression in both benign and malignant prostate disease, and the relationship between their expression and degree of tumour-...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1046/j.1464-410x.2002.02993.x
更新日期:2002-11-01 00:00:00
abstract:OBJECTIVE:To determine whether the addition of ethanol to water for irrigation during transurethral resection of the prostate (TURP) and monitoring breath ethanol could be used to detect irrigant absorption and to limit free plasma haemoglobin in cases of absorption. PATIENTS AND METHODS:One hundred patients (46 in Pi...
journal_title:BJU international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1464-410x.2000.00979.x
更新日期:2000-12-01 00:00:00
abstract:OBJECTIVE:To determine the angiogenic profiles in the bladder of patients with bladder pain syndrome (BPS)/interstitial cystitis (IC), and to evaluate the relationship between these profiles and associated clinical features including pelvic pain and glomerulations. PATIENTS AND METHODS:Angiogenesis and angiogenic comp...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2009.08467.x
更新日期:2009-09-01 00:00:00
abstract:UNLABELLED:What's known on the subject? and what does the study add?: As most urologist known, obesity significantly lowers serum PSA levels. So there is some concern about delayed diagnosis of prostate cancer in obese men. In the present study, we found that the accuracy level of PSA for detecting prostate cancer was ...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2012.11766.x
更新日期:2013-08-01 00:00:00
abstract:OBJECTIVE:To examine the urinary cytological changes caused by flexible cystoscopy and provide clinical guidelines for a reliable time interval for urinary cytological examination after flexible cystoscopy. PATIENTS AND METHODS:Forty-eight patients attending for flexible cystoscopy were recruited into the study. Each ...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2004.04998.x
更新日期:2004-09-01 00:00:00
abstract:UNLABELLED:What's known on the subject? and What does the study add? Positive surgical margins (PSMs) after radical prostatectomy are common, although their impact on the risk of disease recurrence is unknown. We examined the impact of PSMs on the risk of 'significant' biochemical recurrence stratified by their risk of...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2011.10868.x
更新日期:2012-09-01 00:00:00
abstract:UNLABELLED:What's known on the subject? and What does the study add? The common clinical practice for advanced prostatic adenocarcinoma is combination therapy of zoledronic acid (ZA) and docetaxel (TAX). Little is known about the consequences of this combination therapy with regard to osteonecrosis of the jaw (ONJ). Th...
journal_title:BJU international
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1464-410X.2012.11205.x
更新日期:2012-12-01 00:00:00
abstract:OBJECTIVE:To evaluate two methods of reducing the urine output during treatment (the most easily manipulated variable) in patients undergoing intravesical instillation with mitomycin C, where the concentration-time curve also depends upon dose, diluent volume, residual urine volume, and drug absorption and degradation....
journal_title:BJU international
pub_type: 杂志文章
doi:10.1046/j.1464-410x.2000.00869.x
更新日期:2000-10-01 00:00:00
abstract:OBJECTIVES:To examine the effect of the dual-action 5alpha-reductase inhibitor dutasteride on benign prostatic hyperplasia (BPH)-specific health status, as measured by the BPH Impact Index (BII), and to identify baseline and treatment risk factors for those most bothered by their BPH symptoms at the end of the protocol...
journal_title:BJU international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1464-410x.2003.04310.x
更新日期:2003-08-01 00:00:00
abstract:OBJECTIVE:To report our experience of using laparoscopy for the accurate location and simultaneous removal of small dysplastic kidneys with ectopic ureteric insertion causing urinary incontinence and that were not detected by conventional imaging modalities. PATIENTS AND METHODS:Seven girls (mean age 7.9 years, range ...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1046/j.1464-410x.1999.00162.x
更新日期:1999-08-01 00:00:00
abstract:OBJECTIVE:We evaluated the current evidence for the use of acupuncture to treat erectile dysfunction (ED). METHODS:Systematic searches were conducted in 15 electronic databases, with no language restrictions. Hand-searches included conference proceedings and our files. All clinical studies of acupuncture as a treatmen...
journal_title:BJU international
pub_type: 杂志文章,meta分析,评审
doi:10.1111/j.1464-410X.2009.08422.x
更新日期:2009-08-01 00:00:00
abstract:OBJECTIVE:To present the outcomes of cT3N0M0 prostate cancer after radical prostatectomy (RP) and determine the prognostic factors in biochemical progression-free survival (BPFS), clinical progression-free survival (CPFS), cancer-specific survival (CSS) and overall survival (OS) after long-term follow-up of 10 years. ...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2009.09054.x
更新日期:2010-06-01 00:00:00
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journal_title:BJU international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1111/j.1464-410X.2004.05161.x
更新日期:2004-12-01 00:00:00
abstract:UNLABELLED:WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: In renal cell carcinoma the role of lymphadenectomy (LND) is still controversial. Moreover, no firm consensus exists regarding the minimum number of lymph nodes that should be removed to obtain a satisfactory staging LND at the time of surgery. Our f...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2012.11313.x
更新日期:2013-03-01 00:00:00
abstract::OBJECTIVE To describe the rationale and design of the Bladder Cancer Prognosis Programme (BCPP), and to demonstrate the capability of this design. METHODS There is a need to understand the determinants of bladder cancer to help reduce recurrence, progression, morbidity, mortality and related costs. We previously showe...
journal_title:BJU international
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1464-410X.2009.08849.x
更新日期:2010-03-01 00:00:00
abstract:OBJECTIVES:To present long-term oncological outcomes of patients with paratesticular sarcoma treated by a multidisciplinary team. PATIENTS AND METHODS:Patients managed at the Princess Margaret Cancer Centre, between 1990 and 2012, were analysed. A sarcoma expert performed central pathology review. Kaplan-Meier graphs ...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/bju.14775
更新日期:2019-11-01 00:00:00
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journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2007.07016.x
更新日期:2007-08-01 00:00:00
abstract:OBJECTIVE:To report the use of a novel donor source as a further option to increase the number of patients who might be able to receive a renal transplant. PATIENTS AND METHODS:Between May 1996 and July 2007, 43 kidneys were transplanted using kidneys obtained from patients with small (<3 cm diameter) incidentally det...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2008.07562.x
更新日期:2008-07-01 00:00:00
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journal_title:BJU international
pub_type: 杂志文章,评审
doi:10.1111/j.1464-410X.2009.08682.x
更新日期:2009-12-01 00:00:00
abstract:OBJECTIVE:• To examine the prevalence and burden of overactive bladder (OAB) with bother in the UK and Sweden compared to OAB without bother and no/minimal OAB/lower urinary tract (LUTS) symptoms, respectively. PATIENTS AND METHODS:• A cross-sectional population-representative survey was conducted via the Internet in ...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2010.10013.x
更新日期:2011-11-01 00:00:00
abstract:OBJECTIVE:To evaluate the reliability and validity of the Premature Ejaculation Profile (PEP), a self-reported outcome instrument for evaluating domains of PE and its treatment, comprised of four single-item measures, a profile, and an index score. SUBJECTS AND METHODS:Data were from men participating in observational...
journal_title:BJU international
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/j.1464-410X.2008.08041.x
更新日期:2009-02-01 00:00:00
abstract:OBJECTIVE:To obtain community-based information about the incidence of interstitial cystitis, a chronic disabling condition of the bladder where knowledge is limited because there are no definitive diagnostic criteria. PATIENTS AND METHODS:All residents of Olmsted County, MN, USA who had received a physician-assigned ...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1046/j.1464-410x.2003.04060.x
更新日期:2003-02-01 00:00:00
abstract:UNLABELLED:Study Type--Clinical (prospective trial) Level of Evidence 2b. What's known on the subject? and What does the study add? In clinical practice, we know that it is necessary to identify new biomarkers that can better detect prostate cancer (PC), at the same time as reducing the number of unnecessary biopsies. ...
journal_title:BJU international
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1464-410X.2012.11146.x
更新日期:2012-12-01 00:00:00
abstract:OBJECTIVES:To investigate long-term oncological outcomes after laparoscopic radical prostatectomy (LRP). To identify parameters influencing recurrence-free survival in a single-institution series. PATIENTS AND METHODS:All patients underwent LRP using the transperitoneal retrograde Heilbronn technique. High-risk patien...
journal_title:BJU international
pub_type: 杂志文章,评审
doi:10.1111/j.1464-410X.2012.11317.x
更新日期:2013-02-01 00:00:00
abstract:UNLABELLED:What's known on the subject? and What does the study add? Protein kinase C inhibitor (PKCI) can decrease glomerular and tubular cell apoptosis and mitosis and attenuate collagen accumulation and fibronectin expression in a PUUO rat model. Although the role of PKC has been well studied in diabetic nephropathy...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2011.10805.x
更新日期:2012-07-01 00:00:00
abstract::The purpose of this study is to evaluate accuracy of magnetic resonance imaging (MRI) for local staging of bladder cancer for four clinical scenarios (T-stage thresholds) considered against current standards for clinical staging and secondarily to identify sources for variability in accuracy. Systematic review of pati...
journal_title:BJU international
pub_type: 杂志文章,meta分析
doi:10.1111/bju.14366
更新日期:2018-11-01 00:00:00
abstract:STUDY TYPE:Therapy (case series). LEVEL OF EVIDENCE:4. OBJECTIVE:To present our institution's experience of selective embolization of renal angiomyolipomas with alcohol and the long-term follow up data. PATIENTS AND METHODS:This retrospective study included 34 patients treated between October 1997 and October 2007 (...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2009.08813.x
更新日期:2010-02-01 00:00:00
abstract::Advanced adrenal carcinoma remains a significant therapeutic challenge, with conventional approaches to systemic therapy having failed to achieve sustained objective remissions or major survival benefit in most instances. Several systemic therapies, including mitotane, suramin and gossypol, as well as cytotoxic agents...
journal_title:BJU international
pub_type: 杂志文章,评审
doi:10.1111/j.1464-410X.2011.10464.x
更新日期:2011-11-01 00:00:00