Abstract:
:A series of three dose escalating studies were conducted to investigate the ability of the 17alpha-hydroxylase/C(17,20)-lyase inhibitor abiraterone acetate, to cause maximum suppression of testosterone synthesis when delivered to castrate and noncastrate males with prostate cancer. Study A was a single dose study in castrate males. Study B was a single dose study in noncastrate males and study C was a multiple dose study in noncastrate males. The drug was given orally in a once-daily dose and blood samples taken to assess pharmacokinetic (PK) parameters and hormone levels in all patients. The study drug was well tolerated with some variability in PKs. Suppression of testosterone levels to <0.14 nmol l(-1) was seen in four out of six castrate males treated with a single dose of 500 mg. At 800 mg given days 1-12 in noncastrate males, target suppression was achieved in three out of three patients, but a two- to three-fold increase of Luteinising Hormone (LH) levels in two out of three patients overcame suppression within 3 days. All patients in the multiple dose study developed an abnormal response to a short Synacthen test by day 11, although baseline cortisol levels remained normal. This is the first report of the use of a specific 17alpha-hydroxylase/(17,20)-lyase inhibitor in humans. Repeated treatment of men with intact gonadal function with abiraterone acetate at a dose of 800 mg can successfully suppress testosterone levels to the castrate range. However, this level of suppression may not be sustained in all patients due to compensatory hypersecretion of LH. The enhanced testosterone suppression achieved in castrate men merits further clinical study as a second-line hormonal treatment for prostate cancer. Adrenocortical suppression may necessitate concomitant administration of replacement glucocorticoid.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
O'Donnell A,Judson I,Dowsett M,Raynaud F,Dearnaley D,Mason M,Harland S,Robbins A,Halbert G,Nutley B,Jarman Mdoi
10.1038/sj.bjc.6601879subject
Has Abstractpub_date
2004-06-14 00:00:00pages
2317-25issue
12eissn
0007-0920issn
1532-1827pii
6601879journal_volume
90pub_type
临床试验,杂志文章,多中心研究abstract::The influence of vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) on prognosis and the relationship between VEGF expression and MVD in ovarian carcinoma are not well defined. We studied VEGF expression in parallel with MVD by immunohistochemistry in 94 ovarian tumours (64 malignant, 1...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2000.1228
更新日期:2000-07-01 00:00:00
abstract::The topical carcinogenicity to mouse skin of smoke condensates obtained from a tobacco substitute (NSM), alone or in combination with tobacco, has been compared with condensate from tobacco and with acetone, the solvent used. Sixteen different types of cigarette were used to make the condensates, and the age-standardi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1977.47
更新日期:1977-03-01 00:00:00
abstract::In a meta-analysis of testicular cancer in twins, twins had a 30% increased risk (estimate 1.31, 95% CI 1.1-1.6), providing indirect support for the hypothesis that in utero hormone variations influence risk of testicular cancer. The summary-estimate for dizygotic twins was 1.3 (1.0-1.7) and for monozygotic or same se...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1038/sj.bjc.6604136
更新日期:2008-01-15 00:00:00
abstract:BACKGROUND:Colonoscopic surveillance provides the best practical means for preventing colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients. Strong evidence for improved survival from surveillance programmes is sparse. METHOD:The aim of this study was to compare tumour stage and survival of IBD patients...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605359
更新日期:2009-11-17 00:00:00
abstract::The carcinoembryonic antigen (CEA) was produced and released by human colorectal carcinomata and also the normal attached mucosa when maintained in both monolayer and organ culture. Immunoperoxidase cytochemical methods were employed for the cellular localization of CEA which was demonstrable only on the neoplastic ce...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1975.97
更新日期:1975-05-01 00:00:00
abstract::Hypoxic EMT-6 tumour cells displayed a high level of inducible nitric oxide synthase (iNOS) and an increased radiosensitivity after a 16 h exposure to lipopolysaccharide, a known activator of nuclear factor-kappaB (NF-kappaB). Both iNOS activation and radioresponse were impaired by the NF-kappaB inhibitors phenylarsin...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600678
更新日期:2003-01-13 00:00:00
abstract::Darbepoetin alfa (Aranesp), Amgen) is a novel erythropoiesis-stimulating protein with a serum half-life longer than recombinant human erythropoietin (Epo), used in the treatment of cancer-associated anaemia. Anaemia is known to adversely affect prognosis and response to treatment in cancer patients. Solid tumours cont...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602685
更新日期:2005-07-25 00:00:00
abstract::Clonal subpopulations of different ploidy values and metastatic capacities, isolated from the RIF-1 mouse sarcoma, have been tested for in vitro X-radiation sensitivity, for in vitro sensitivity to adriamycin and for in vitro and in vivo sensitivity to melphalan and CCNU. Following X-radiation, no consistent differenc...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1983.139
更新日期:1983-06-01 00:00:00
abstract::The aim of the study was to evaluate efficacy and tolerance of epirubicin and gemcitabine as first-line chemotherapy in patients with advanced non-small-cell lung cancer. A phase I study was performed with the combination of escalating doses of epirubicin intravenously on day 1 and a fixed dose of gemcitabine on days ...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1054/bjoc.1999.1003
更新日期:2000-02-01 00:00:00
abstract:BACKGROUND:The potential for cancer-testis (CT) antigens as targets for immunotherapy in cancer patients has been heavily investigated, and currently cancer vaccine trials based on the CT antigens, MAGE-A3 and NY-ESO-1, are being carried out. METHODS:We used specific q-RT-PCR assays to analyse the expression of the CT...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.215
更新日期:2012-06-26 00:00:00
abstract::The tumour suppressor gene CDKN2A, located on chromosome 9p21, encodes the cell cycle regulatory protein p16. Inactivation of the CDKN2A gene could lead to uncontrolled cell growth. In order to determine the role of CDKN2A in the development of sporadic ovarian cancer, loss of heterozygosity at 9p21-22, homozygous del...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690621
更新日期:1999-08-01 00:00:00
abstract:BACKGROUND:This randomised controlled trial examined the impact of screening for distress followed by two different triage methods on clinically relevant outcomes over a 12-month period. METHODS:Newly diagnosed patients attending a large tertiary cancer centre were randomised to one of the two conditions: (1) screenin...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1038/bjc.2012.309
更新日期:2012-08-07 00:00:00
abstract::One hundred resected cases of squamous cell carcinomas of the oesophagus were reviewed and a series of histological criteria related to the survival time. Two histological features were important in the assessment of survival. Good prognostic factors were a marked lymphocytic response to the tumour and a lack of intra...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.87
更新日期:1989-03-01 00:00:00
abstract::Secular, socioeconomic and urban-rural gradients and geographical differences in beef and fat consumption within the United States of America are compared with corresponding data on colorectal cancer incidence and mortality rates. These results, together with the results of most previous epidemiological studies, appea...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1975.244
更新日期:1975-10-01 00:00:00
abstract::Local recurrence of glioblastomas is a major cause of patient mortality after definitive treatment. This review discusses the roles of the chemokine stromal cell-derived factor-1 and its receptor CXC chemokine receptor 4 (CXCR4) in affecting the sensitivity of glioblastomas to irradiation. Blocking these molecules pre...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/bjc.2011.169
更新日期:2011-06-07 00:00:00
abstract::Germline anomalies of the INK4a-ARF and Cdk4 genes were sought in a series of 89 patients suspected of having a genetic predisposition to melanoma. Patients were selected based on the following criteria: (a) familial melanoma (23 cases), (b) multiple primary melanoma (MPM; 18 cases), (c) melanoma and additional unrela...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601503
更新日期:2004-01-26 00:00:00
abstract::In this study, the role of parity in conferring protection of the mammary gland against chemical carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) was investigated. Experiments were also carried out to determine if an 'interrupted' pregnancy was capable of reducing the incidence of mammary tumour inducti...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.88
更新日期:1988-04-01 00:00:00
abstract:BACKGROUND:The risk and prognosis of ovarian cancer have not been well established in women with endometriosis. Thus, we investigated the impact of endometriosis on the risk and prognosis for ovarian cancer, and evaluated clinicopathologic characteristics of endometriosis-associated ovarian cancer (EAOC) in comparison ...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1038/bjc.2014.29
更新日期:2014-04-02 00:00:00
abstract::We investigated the feasibility and the anti-tumour activity of weekly cisplatin and the simultaneous application of local hyperthermia in patients with a pelvic recurrence of cervical cancer in previously irradiated area. Dose levels of cisplatin 60 mg m(-2), 70 mg m(-2) and 80 mg m(-2) were studied. Treatment object...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6690533
更新日期:1999-07-01 00:00:00
abstract::BGC9331 is a rationally designed, specific nonpolyglutamatable thymidylate synthase (TS) inhibitor that is active in gynaecological malignancies. In the light of the sensitivity of human ovarian tumour cell lines to BGC9331 and non-cross resistance to platinum drugs, we studied the combination BGC9331/carboplatin (BCA...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6602811
更新日期:2005-10-17 00:00:00
abstract::Ninety-two consecutive adult patients admitted with acute life-threatening complications of haematological malignancy were studied to determine long term outcome. The quality of life was evaluated in seven long term survivors who are currently alive more than 1 year after hospital discharge using three validated metho...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1991.430
更新日期:1991-11-01 00:00:00
abstract::We investigated the predictors of the risk of developing a second primary cancer after breast cancer, this occurring in about 12% of affected women. The analysis included 335 191 females, registered in the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database, who had been diagnosed wit...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603172
更新日期:2006-06-05 00:00:00
abstract::Temozolomide is an oral alkylating agent that readily crosses the blood-brain barrier and has activity in patients with advanced melanoma. Carboplatin is a convenient outpatient treatment that also has activity in patients with melanoma. The purpose of this study was to assess the safety of a combination of temozolomi...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6601414
更新日期:2003-11-17 00:00:00
abstract::The present study investigates the role of nitric oxide and the involvement of nitric oxide synthase II isoform on the invasion of human colorectal adenocarcinoma cell lines HRT-18 and HT-29. HRT-18 cells, which constitutively express nitric oxide synthase II mRNA were three-fold more invasive in a Matrigel invasion a...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600224
更新日期:2002-04-22 00:00:00
abstract::In the years 1979-1982, 83 patients with malignant teratoma of the testis who had retroperitoneal adenopathy at presentation or after a period of surveillance were treated. Complete radiological resolution of disease was obtained in 34 patients and a residual mass remained in 26, the remainder having progression of th...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1986.105
更新日期:1986-05-01 00:00:00
abstract::Recepteur d'Origine Nantais (RON) is a distinct receptor tyrosine kinase in the c-met proto-oncogene family. We examined the mutational and expression patterns of RON in eight human uroepithelial cell lines. Biological effects of RON overexpression on cancer cells were investigated in vitro, and the prognostic signifi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602593
更新日期:2005-05-23 00:00:00
abstract:BACKGROUND:The prognostic and predictive value of multiple serum biomarkers was evaluated using samples from a randomised phase III study (HORIZON II) investigating chemotherapy with or without cediranib in metastatic colorectal cancer (mCRC). METHODS:Baseline levels of 207 protein markers were measured in serum sampl...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1038/bjc.2013.649
更新日期:2013-11-26 00:00:00
abstract:BACKGROUND:The role of further hormone therapy in castration-resistant prostate cancer (CRPC) remains unclear. We performed a multi-centre randomised phase III study comparing the use of Dexamethasone, Aspirin, and immediate addition of Diethylstilbestrol (DAiS) vs Dexamethasone, Aspirin, and deferred (until disease pr...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/bjc.2011.7
更新日期:2011-02-15 00:00:00
abstract::Records of approximately 310,000 patients admitted to the 10 hospitals in Botswana between 1960 and 1972 have been studied and details of 1445 patients with malignant tumours abstracted. For the 894 tumours for which there was some supporting evidence--at best histological proof and minimally a clinical description of...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1975.138
更新日期:1975-07-01 00:00:00
abstract:BACKGROUND:This phase 1 study examined the safety, tolerability, pharmacokinetics and preliminary efficacy of eribulin-liposomal formulation (eribulin-LF) in patients with advanced solid tumours. METHODS:Eligible patients with ECOG PS 0-1 were treated with eribulin-LF either on day 1 every 21 days (Schedule 1), or on ...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/s41416-019-0377-x
更新日期:2019-02-01 00:00:00