Abstract:
BACKGROUND:This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with paclitaxel. METHODS:A total of 22 patients received paclitaxel (135-175 mg m(-2)) intravenously, administered once every three weeks for up to six cycles, with oral tosedostat (90-240 mg) daily. RESULTS:One DLT (grade 3 dyspnoea) was observed in one patient with tosedostat 180 mg combined with paclitaxel 175 mg m(-2). A high number of paclitaxel infusion reactions was noted during the second administration (59%) and this prompted interruption of tosedostat dosing for 5 days around every second and subsequent paclitaxel infusion. No formal MTD was determined because of the high frequency of paclitaxel infusion reactions that may have been influenced by tosedostat. Most frequently observed drug-related adverse events were alopecia, fatigue (95% each), peripheral sensory neuropathy (59%), paclitaxel hypersensitivity (59%) and rash (55%). One patient died because of eosinophilic myocarditis, possibly related to study medication. There was no PK interaction between tosedostat and paclitaxel. In all, 3 patients had a partial response and 12 patients had stable disease lasting >3 months. CONCLUSION:The combination of tosedostat with paclitaxel was well tolerated except for the high incidence of paclitaxel-related infusion reactions.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
van Herpen CM,Eskens FA,de Jonge M,Desar I,Hooftman L,Bone EA,Timmer-Bonte JN,Verweij Jdoi
10.1038/sj.bjc.6605917subject
Has Abstractpub_date
2010-10-26 00:00:00pages
1362-8issue
9eissn
0007-0920issn
1532-1827pii
6605917journal_volume
103pub_type
杂志文章abstract::The overall tumour incidence and breast cancer incidence related to hormone replacement therapy (HRT) were followed in a population-based cohort of 29 508 women, aged 25-65 when interviewed in 1990-92. By the end of the follow up in December 1999, there were 226 611 person-years of observation. A total of 1145 maligna...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.1899
更新日期:2001-09-01 00:00:00
abstract:BACKGROUND:Identification of promising biomarkers that predict the prognosis of patients with breast cancer is needed. In this study, we hypothesised that the expression of the epithelial-mesenchymal transition-related biomarker plastin3 (PLS3) in peripheral blood could be a prognostic factor in breast cancer. METHODS...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2015.132
更新日期:2015-04-28 00:00:00
abstract::The use of oncolytic viruses has received considerable attention in recent years and many viruses have proved to be effective against a variety of cancer models and a few are currently being used in clinical trials. However, the possible emergence and outcome of virus-resistant tumour cells has not been addressed. We ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603363
更新日期:2006-10-23 00:00:00
abstract::Serum levels of the soluble epidermal growth factor receptor (sEGFR) and its ligands epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha) and amphiregulin (AR) were measured in healthy donors and patients with non-small cell lung cancer (NSCLC) and head and neck carcinoma (HNC). In NSCLC, we fou...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603770
更新日期:2007-05-21 00:00:00
abstract::Lysophosphatidic acid (LPA) is a potent lipid mediator that acts on a series of specific G protein-coupled receptors, leading to diverse biological actions. Lysophosphatidic acid induces cell proliferation, survival and migration, which are critically required for tumour formation and metastasis. This bioactive lipid ...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6605588
更新日期:2010-03-16 00:00:00
abstract::Forty-two patients with small cell lung cancer were treated with a combination of carboplatin, ifosfamide and etoposide. Vincristine was given on day 14 of each course, the courses being repeated every 28 days for a maximum of six. Thoracic radiotherapy was given 4 weeks after the last course of chemotherapy but no pr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.228
更新日期:1989-07-01 00:00:00
abstract::Low-dose hyper-radiosensitivity (HRS) (below 0.5 Gy) has been extensively documented in the past few years. The molecular basis of this phenomenon remains largely unknown and the purpose of this study was to investigate the possible implication of the DNA repair DNA-PK complex. The activity of the DNA-PK complex, i.e....
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2000.1258
更新日期:2000-08-01 00:00:00
abstract::Currently, there are no effective biomarkers for ovarian cancer prognosis or prediction of therapeutic response. The objective of this study was to examine a panel of 10 serum biochemical parameters for their ability to predict response to chemotherapy, progression and survival of ovarian cancer patients. Sera from ov...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604630
更新日期:2008-10-07 00:00:00
abstract::Twenty patients with non-Hodgkin's lymphoma were treated with a combination of cyclophosphamide (750 mg m(-2), day 1), epidoxorubicin (60 mg m(-2), day 1), vincristine (1.4 mg m(-2), day 1) and prednisone (100 mg m(-2), days 1-5) every 14 days. Shortening of intervals was associated with the prophylactic employment of...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1998.578
更新日期:1998-09-01 00:00:00
abstract::A standardised, effective systemic therapy for metastatic neuroendocrine tumours (NETs) has not been established to date. We reviewed the management of 15 patients with inoperable, metastatic NET treated systematically with a combination chemotherapy regimen of infusional 5-fluorouracil, folinic acid and streptozocin....
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601167
更新日期:2003-08-04 00:00:00
abstract:BACKGROUND:Anoctamin (ANO)/transmembrane member 16 (TMEM16) proteins mediate diverse physiological and pathophysiological functions including cancer cell proliferation. The present study aimed to identify the role of ANOs in pancreatic cancer. METHODS:In an initial screen of ANOs, ANO9/TMEM16J was overexpressed in pan...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2017.355
更新日期:2017-12-05 00:00:00
abstract::In order to elucidate the clinical significance of the erbB family, epidermal growth factor receptor (EGF-R), c-erbB-2, c-erbB-3 and c-erbB-4 in hepatocellular carcinoma (HCC), we investigated the expression of these proteins by means of immunohistochemistry for HCC as well as adjacent noncancerous lesions. EGF-R was ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2000.1580
更新日期:2001-05-18 00:00:00
abstract:BACKGROUND:Recent studies suggest that older patients in the United Kingdom are not benefiting as much from improvements in cancer treatments as their younger counterparts. We investigate whether this might be partly due to differential referral rates using ovarian cancer as an example. METHODS:From the General Practi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605593
更新日期:2010-03-16 00:00:00
abstract:BACKGROUND:Vascular endothelial growth factor (VEGF)-mediated angiogenesis mediates tumour growth and metastasis. Meningiomas are primarily benign, slow-growing, highly vascularised tumours. Aside from VEGF, there is little data on the function of major angiogenic proteins in meningiomas. METHODS:The VEGFA, platelet-d...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.459
更新日期:2012-11-06 00:00:00
abstract::A follow-up study of 1844 renal transplant patients in Italy showed a 113-fold increased risk for Kaposi's sarcoma. Kaposi's sarcoma risk was higher in persons born in southern than in northern Italy. Significant increases were also observed for cancers of the lip, liver, kidney and for non-Hodgkin's lymphoma. ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602346
更新日期:2005-02-14 00:00:00
abstract::An enzyme activity with the characteristics of reverse transcriptase was detected in marrow from patients with leukaemia in relapse and in firm haematological remission. The endogenous enzyme activities increased following culture, and in remission patients the enzyme activities reached levels equal to or exceeding th...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1974.95
更新日期:1974-06-01 00:00:00
abstract::We reviewed 134 patients with breast cancer (screen detected = 85, interval = 49) who had been reported as negative at previous mammographic screening in the Florence District Programme. At prior mammograms review, 12% of the cases were classified as 'screening error' (suspicious signs missed owing to misperception or...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.67
更新日期:1995-02-01 00:00:00
abstract::Flavone acetic acid (FAA) was administered at a dose of 4.8 g m-2 over 1 h to patients with advanced malignant disease in combination with Interleukin II. A new high performance liquid chromatography method is described to determine both the parent compound and eight drug-related products, and the conditions required ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.250
更新日期:1993-06-01 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:BACKGROUND:To prospectively examine the association between diabetes and risk of prostate cancer defined by clinical and molecular features. METHODS:A total of 49,392 men from the Health Professionals Follow-up Study (HPFS) were followed from 1986 to 2014. Data on self-reported diabetes were collected at baseline and ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-0910-y
更新日期:2020-08-01 00:00:00
abstract::The histological breakdown of a consecutive series of 264 surgically resected malignant lesions of the breast was studied. Oestrogen and epidermal growth factor receptor status was quantified and presented along with size and lymph node status of the non-ductal lesions. Those non-ductal tumours containing EGF receptor...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.240
更新日期:1988-10-01 00:00:00
abstract:BACKGROUND:The integrin-binding protein osteopontin is strongly associated with tumour development, yet is an abundant dietary component as a constituent of human and bovine milk. Therefore, we tested the effect of orally administered osteopontin (o-OPN) on the development of subcutaneous tumours in mice. METHODS:Bovi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.10
更新日期:2014-03-04 00:00:00
abstract:BACKGROUND:Consumption of wholegrain (WG) products may protect against colon and rectal cancer. METHODS:The associations between total and individual WG product consumption and colon and rectal cancer risk were prospectively examined using data on 461 incident cases of colon cancer and 283 incident cases of rectal can...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605806
更新日期:2010-08-24 00:00:00
abstract::The important role of the p53 gene in tumour progression and cellular response to DNA damage has prompted investigation of the clinical significance of alterations to this gene. We examined both p53 overexpression and mutation of the gene in endometrial carcinoma in order to evaluate the prognostic significance of the...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.401
更新日期:1996-08-01 00:00:00
abstract::To test the anti-tumour activity of rhizoxin in recurrent and/or metastatic squamous cell head and neck cancer, we performed a phase II study. Eligibility required histologically proven squamous cell head and neck cancer. Patients could only have received one prior chemotherapy. Patients were entered if WHO PS was < o...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1038/bjc.1996.69
更新日期:1996-02-01 00:00:00
abstract::Human monocytes can be induced to synthesize a cytotoxin which affects certain tumour cell lines. The interaction of monocyte cytotoxin with a susceptible cell line (L929) has been studied to obtain clues to the mode of action of the cytotoxin. The cytotoxin acts directly on the cells rather than on the culture medium...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1983.205
更新日期:1983-09-01 00:00:00
abstract::Tumour necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL/APO2L) is a recently identified member of the TNF family, which induces programmed cell death in a variety of neoplastic cell types, but not in most nonneoplastic cells. In this study, we report on the identification of two novel alternative splice ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600772
更新日期:2003-03-24 00:00:00
abstract::Serum laminin P1 was studied in patients with small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), respiratory infections, pulmonary fibrosis, and in normal subjects. The level of serum laminin P1 was elevated (greater than 1.27 U ml-1) in 58.9% of SCLC and in 11.5% of NSCLC patients. Median value in SCL...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.123
更新日期:1992-04-01 00:00:00
abstract:BACKGROUND:Among patients with cancer, prior research suggests that patients with mental illness may have reduced survival. The objective was to assess the impact of psychiatric utilisation (PU) prior to cancer diagnosis on survival outcomes. METHODS:All residents of Ontario diagnosed with one of the top 10 malignanci...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-019-0390-0
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:To quantify the benefits (cancer prevention and down-staging) and harms (recall and excess treatment) of cervical screening starting from age 20 years rather than from age 25 years. METHODS:We use routine screening and cancer incidence statistics from Wales (for screening from age 20 years) and England (scr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.65
更新日期:2014-04-02 00:00:00