Abstract:
UNLABELLED:What's known on the subject? and What does the study add? To date, there has been limited impetus to examine the use of cytarabine in prostate cancer. We presented preliminary laboratory data to suggest its utility in the castration refractory prostate cancer (CRPC) population which, combined with a previous case report, suggested it may have hitherto unrecognized utility in this setting. Embedded in this study was peripheral blood sampling for TMPRSS2-ERG and SPINK1, two genes that are believed to define prostate cancer genotypes, to assess their utility as biomarkers This study suggests that at the delivered doses, cytarabine has limited efficacy and significant myelotoxicity suggesting, it does not have a role in the treatment of docetaxel-refractory CRPC. The presence of serum TMPRSS2-ERG and SPINK1 mRNA biomarkers recovered from blood suggest that their analysis is worthy of further study. OBJECTIVES:To run a phase II clinical trial of cytarabine in men with docetaxel-refractory, castration-resistant prostate cancer (CRPC), based on evidence that cytarabine might be effective in men with abnormalities of ERG oncogenes. To measure mRNA levels of prostate cancer-related genes in blood as biomarkers. PATIENTS AND METHODS:Ten of a planned maximum of 30 men received i.v. cytarabine at doses of 0.25-1g/m(2) at 21-day intervals. The primary endpoint was prostate-specific antigen (PSA) response. Archival tumour samples were assessed by fluorescence in-situ hybridization for TMPRSS2:ERG translocation, and by immunohistochemistry for serine peptidase inhibitor Kazal type 1 (SPINK1). Blood was processed for mRNA quantification of TMPRSS2:ERG (exon1:exon4), SPINK1 and PSA. RESULTS:A PSA response was not observed in any patient. The trial was stopped at the end of stage 1 of a modified Flemming design. The median number of cycles administered was 3. Grade 3-4 haematological toxicity was common. Five patients were subsequently excluded from the study for toxicity, and five for disease progression. Analysis of whole blood mRNA for T1:E4 translocation in TMPRSS2:ERG was consistent with that in the tumour in 8/9 evaluable cases (one was concordantly positive, seven were concordantly negative), SPINK1 results were concordant in 9/10 cases (two were concordantly positive, seven were concordantly negative [P = 0.047 for the predictive value]). There was no correlation between PSA or SPINK protein and their respective mRNA copy levels in blood. CONCLUSIONS:Cytarabine at the doses used is ineffective for men with CRPC. Blood mRNA levels of prostate cancer genes may represent a novel aspect of monitoring prostate cancer and have implications for the understanding of tumour-derived mRNA.
journal_name
BJU Intjournal_title
BJU internationalauthors
Dhani NC,Emmenegger U,Adams L,Jongstra J,Tannock IF,Sridhar SS,Knox JJ,Day JR,Groskopf J,Joshua AMdoi
10.1111/j.1464-410X.2011.10922.xsubject
Has Abstractpub_date
2012-09-01 00:00:00pages
840-5issue
6eissn
1464-4096issn
1464-410Xjournal_volume
110pub_type
杂志文章abstract:OBJECTIVE:To determine whether very small prostate cancers present in patients who also have lymph node (LN) metastases represent a particularly aggressive disease variant compared with larger LN-positive tumours. PATIENTS AND METHODS:We identified 37 501 patients diagnosed with prostate cancer between 1988 and 2001 t...
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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 ...
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abstract:OBJECTIVE:To optimise the diagnostic and phototherapeutic efficacy of hypericin in superficial bladder cancer, by developing a bladder instillation fluid that does not depend on the presence of plasma proteins for an appropriate and reliable urothelial uptake of hypericin. MATERIALS AND METHODS:Sodium hypericinate (in...
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abstract:OBJECTIVE:To investigate the effect of dutasteride and tamsulosin as combined therapy compared with each monotherapy for improving patient-reported health outcomes in men with moderate-to-severe urinary symptoms and prostate enlargement, reporting the pre-planned 2-year analyses from the CombAT trial. PATIENTS AND MET...
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pub_type: 杂志文章,多中心研究,随机对照试验
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abstract:OBJECTIVE:To determine some of the genetic alterations involved in the pathogenesis and progression of transitional cell carcinoma of the bladder. Materials and methods In a population-based study, freshly frozen tissue was collected from all patients newly diagnosed with urinary bladder cancer in the Stockholm region ...
journal_title:BJU international
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doi:10.1046/j.1464-410x.2001.02212.x
更新日期:2001-06-01 00:00:00
abstract:OBJECTIVE:To compare changes in regional cerebral blood flow (rCBF), using positron emission tomography (PET), during chronic and acute sacral neuromodulation (SN). SN is an effective long-term treatment for chronic urge incontinence due to urinary bladder hyperactivity, as sensory nerves, spinal and supraspinal struct...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2006.06521.x
更新日期:2006-12-01 00:00:00
abstract:OBJECTIVES:To compare the serum levels of insulin-like growth factor-1 (IGF-1) in patients with prostate cancer and in control patients with no malignancy, and to evaluate any possible influence of testicular androgen withdrawal on the level of IGF-1 in patients with prostate cancer. PATIENTS AND METHODS:IGF-1 was mea...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1046/j.1464-410x.2000.00350.x
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pub_type: 杂志文章
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journal_title:BJU international
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doi:10.1111/j.1464-410X.2008.08163.x
更新日期:2009-04-01 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
doi:10.1046/j.1464-410x.2001.00084.x
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更新日期:2001-03-01 00:00:00
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更新日期:2006-12-01 00:00:00
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更新日期:2007-07-01 00:00:00
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更新日期:2009-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:2007-03-01 00:00:00
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更新日期:2003-11-01 00:00:00
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更新日期:2013-08-01 00:00:00
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更新日期:2008-06-01 00:00:00