Abstract：
:To assess tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical activity of the dual epidermal growth factor receptor (EGFR) 1 and 2 (HER2) tyrosine kinase inhibitor BIBW 2992. An escalating schedule of once-daily (OD) BIBW 2992 for 14 days followed by 14 days off medication was explored. Thirty-eight patients were enrolled. Dose levels were 10, 20, 30, 45, 70, 85, and 100 mg. At 100 mg dose-limiting toxicity (DLT) (common toxicity criteria grade 3 skin rash and grade 3 diarrhoea despite treatment with loperamide) occurred in two patients. In the next-lower dose of 70 mg, DLT (grade 3 fatigue and ALAT elevation) occurred in one of six patients. An intermediate dose level of 85 mg was studied. Here DLT occurred in two patients (grade 3 diarrhoea despite treatment and grade 2 diarrhoea lasting more than 7 days despite treatment). An additional 12 patients were treated at 70 mg. BIBW 2992 PK after single and multiple doses revealed moderately fast absorption, and no deviation from dose proportionality. Pharmacodynamics analysis in skin biopsies did not show significant changes in EGFR-associated biomarkers. However, a significant inhibitory effect on the proliferation index of epidermal keratinocytes was observed. No partial or complete responses were observed, stable disease lasting more than four cycles was seen in seven patients. The recommended dose for studies with BIBW 2992 for 14 days followed by 14 days off medication is 70 mg OD.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Eskens FA,Mom CH,Planting AS,Gietema JA,Amelsberg A,Huisman H,van Doorn L,Burger H,Stopfer P,Verweij J,de Vries EGdoi
10.1038/sj.bjc.6604108subject
Has Abstractpub_date
2008-01-15 00:00:00pages
80-5issue
1eissn
0007-0920issn
1532-1827pii
6604108journal_volume
98pub_type
杂志文章abstract：:Despite encouraging results from recent studies, there is still no consensus to undertake mass screening using the Haemoccult test in the general population. The success of mass screening for colorectal cancer depends among other things on Haemoccult test properties. In on-going screening programmes, the Haemoccult te...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.459
更新日期：1995-10-01 00:00:00
abstract：BACKGROUND:The role of tumour-infiltrating inflammation in the prognosis of patients with colorectal cancer (CRC) has not been fully evaluated. The primary objective of our meta-analysis was to determine the impact of tumour-infiltrating inflammation on survival outcomes. METHODS:Ovid MEDLINE and EMBASE were searched ...
journal_title：British journal of cancer
pub_type： 杂志文章,meta分析,评审
doi：10.1038/bjc.2014.46
更新日期：2014-03-18 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：:Geographical correlations between standardized, mortality ratios (SMRs) of cancers and consumption of different types of alcoholic beverages (saké synthetic saké, shochu, beer, wine, and whisky), of cigarettes, and urbanization were examined for all 46 prefectures in Japan. Suggestive correlations were observed betwee...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1979.200
更新日期：1979-09-01 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 survival and clonogenic growth (measured in terms of colony forming efficiency (CFE) of intravenously injected (i.v.) Walker (W256) tumour cells in the lungs of rats was greatly enhanced by states of topical and systemic stress induced by the intraperitoneal (i.p.) injection of rats with a single dose of 10(-5)-10...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1976.7
更新日期：1976-01-01 00:00:00
abstract：:Our purpose was to determine the response rate and median and overall survival of gemcitabine as monotherapy versus gemcitabine plus irinotecan in advanced or metastatic pancreatic cancer. Patients with histologically or cytologically confirmed adenocarcinoma who were chemotherapy and radiotherapy naive were enrolled....
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/sj.bjc.6603301
更新日期：2006-09-04 00:00:00
abstract：:One hundred and one histologically confirmed gastric cancer patients in Gwynedd, North Wales, were matched by sex, age and social class to two hospital inpatients without cancer. Seventy-seven of the gastric cancer cases were also matched, using the same criteria, to a patient with a confirmed cancer of a different si...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1990.165
更新日期：1990-05-01 00:00:00
abstract：BACKGROUND:We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to-hip ratio, WHR), which may better reflect metabolic complications of obes...
journal_title：British journal of cancer
pub_type： 杂志文章,meta分析
doi：10.1038/bjc.2017.106
更新日期：2017-05-23 00:00:00
abstract：:The purpose of the study is to test the hypothesis that expression of cell cycle regulatory proteins p16(INK4a) and pRb is significantly associated with prognosis in ovarian carcinomas. We performed immunohistochemical analysis of p16(INK4a) and pRb expression and correlated with survival in a series of 300 patients w...
journal_title：British journal of cancer
pub_type： 杂志文章,随机对照试验
doi：10.1038/sj.bjc.6603531
更新日期：2007-01-29 00:00:00
abstract：:Serine proteases, such as alpha-chymotrypsin or elastase, caused an aggregation of rat ascites tumour cell lines, AH-130, AH-109A and YS, in a protein free medium which preserved the cell viability. This aggregation, which was monitored spectrophotometrically, was dependent upon the protease activities and was resista...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1990.339
更新日期：1990-10-01 00:00:00
abstract：:Targeting growth-regulatory pathways is a promising approach in cancer treatment. A prerequisite to the development of such therapies is characterisation of tumour growth regulation in the particular tumour cell type of interest. In order to gain insight into molecular mechanisms underlying proliferative responses in ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602535
更新日期：2005-04-25 00:00:00
abstract：:DNA flow cytometry was performed on formalin fixed, paraffin embedded melanocytic naevi. DNA aneuploidy was detected in all three types of naevus but was significantly more frequent in those naevi accepted as precursors of malignancy: that is, dysplastic and congenital pigmented hairy naevi. It may be that the presenc...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.268
更新日期：1988-11-01 00:00:00
abstract：:We assessed the association of postmenopausal serum levels of oestrogens and sex hormone-binding globulin (SHBG) with endometrial cancer risk in a case-control study nested within the NYU Women's Health Study cohort. Among 7054 women postmenopausal at enrolment, 57 cases of endometrial cancer were diagnosed a median o...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.1704
更新日期：2001-04-06 00:00:00
abstract：:Increasingly, treatment choices leading to the same survival outcome can be offered to cancer patients (e.g. mastectomy or conservative surgery in early breast cancer). Two approaches available for post-orchidectomy, stage I patients with non-seminomatous germ cell tumours of the testis (NSGCTT), particularly those at...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.570
更新日期：1996-11-01 00:00:00
abstract：BACKGROUND:Cutaneous melanoma is the most serious skin malignancy and new therapeutic strategies are needed for advanced melanoma. TP53 mutations are rare in cutaneous melanoma and hence activation of wild-type p53 is a potential therapeutic strategy in cutaneous melanoma. Here, we investigated the WIP1 inhibitor, GSK2...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2017.433
更新日期：2018-02-20 00:00:00
abstract：BACKGROUND:We used bleomycin, etoposide, cisplatin (BEP), the most effective regimen in the treatment of germ cell tumours (GCTs) and increased dose-density by using pegfilgrastim to shorten cycle length. Our aim was to assess safety and tolerability. METHODS:Sixteen male patients with intermediate or poor prognosis m...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.309
更新日期：2011-09-06 00:00:00
abstract：:Previous studies have shown that multidrug resistance (MDR) in the doxorubicin-selected lung tumour cell lines COR-L23/R, GLC4/ADR and MOR/R is associated with overexpression of the MRP gene. In this study we report that resistance to daunorubicin, vincristine and rhodamine 123 can be partially reversed in these cell ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.281
更新日期：1995-07-01 00:00:00
abstract：:Advances in understanding the role of vascular endothelial growth factor (VEGF) in normal physiology are giving insight into the basis of adverse effects attributed to the use of VEGF inhibitors in clinical oncology. These effects are typically downstream consequences of suppression of cellular signalling pathways imp...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/sj.bjc.6603813
更新日期：2007-06-18 00:00:00
abstract：:In the family reported here, a mother and both of her children developed a Wilms tumour, and all three tumours were of the relatively rare monomorphous epithelial histopathological subtype. Using restriction fragment length polymorphism analysis, both sibs were shown to inherit the same maternal allele from the 11p13 ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.210
更新日期：1994-06-01 00:00:00
abstract：:Sera from 182 newly diagnosed breast cancer patients were assayed for antibodies to p53 using an enzyme-linked immunosorbent assay (ELISA) method, and antibodies were detected in 48 (26%) compared with 1 out of 76 (1.3%) normal control volunteers (P = 0.0001). In breast cancer patients, autoantibodies were found in al...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.219
更新日期：1994-06-01 00:00:00
abstract：BACKGROUND:Surgery is considered to be the first line treatment for solid tumours. Recently, retrospective studies reported that general anaesthesia was associated with worse long-term cancer-free survival when compared with regional anaesthesia. This has important clinical implications; however, the mechanisms underly...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.426
更新日期：2014-09-23 00:00:00
abstract：BACKGROUND:The aim of this work was to improve the knowledge of the role of histamine in breast cancer by assessing the therapeutic efficacy of histamine and histamine H4 receptor (H4R) ligands in a triple-negative breast cancer (TNBC) model developed in immunocompetent hosts. By using publicly available genomic data, ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-019-0636-x
更新日期：2020-02-01 00:00:00
abstract：:Karyotyping and marker analysis of G- and C-banded metaphases from a metastatic bronchial carcinoma revealed a dominant stemline with five markers and four sidelines with additional markers. One to three minute bodies were noted in the majority of cells and these were classified as markers. On the basis of this analys...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1976.162
更新日期：1976-09-01 00:00:00
abstract：:The p53 tumour suppressor protein inhibits malignant progression by mediating cell cycle arrest, apoptosis or repair following cellular stress. One of the major regulators of p53 function is the MDM2 protein, and multiple forms of cellular stress activate p53 by inhibiting the MDM2-mediated degradation of p53. Mutatio...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1054/bjoc.2001.2128
更新日期：2001-12-14 00:00:00
abstract：BACKGROUND:Oral squamous cell carcinoma (OSCC) has increased morbidity, and its high metastatic potential affects patient survival. Bromodomain containing 4 (BRD4) is a chromatin protein that associates with acetylated histone lysines and facilitates transcription. BRD4 has been implicated in cell proliferation, metast...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-0907-6
更新日期：2020-08-01 00:00:00
abstract：:We have evaluated the relation between cancer of the lower urinary tract ("bladder cancer") and the use of artificial sweeteners, by means of case-control studies in Manchester, U.K., and Nagoya, Japan, areas where extensive use occurred 30-40 years ago. In each area, a broadly based series of cases (555 in Manchester...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1982.59
更新日期：1982-03-01 00:00:00
abstract：:Human primary thyroid follicular epithelial cells were transfected with a plasmid containing an origin-defective SV40 genome (SVori-) to produce several immortal cell lines. Two of the 10 cell lines analysed expressed specific features of thyroid epithelial function (iodide-trapping and thyroglobulin production). Thes...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.387
更新日期：1989-12-01 00:00:00
abstract：BACKGROUND:In neuroblastoma (NB), the most powerful prognostic marker, the MYCN amplification (MNA), occasionally shows intratumoural heterogeneity (ITH), i.e. coexistence of MYCN-amplified and non-MYCN-amplified tumour cell clones, called heterogeneous MNA (hetMNA). Prognostication and therapy allocation are still uns...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究
doi：10.1038/s41416-018-0098-6
更新日期：2018-05-01 00:00:00
abstract：:The relationship between oestrogen receptor (RE) content of primary breast cancer and subsequent prognosis was examined with regard to nodal status. It was found that, within a particular nodal group, patients with tumours containing fully functional RE experienced a longer disease-free interval than those with RE- di...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.9
更新日期：1981-01-01 00:00:00
