Abstract：
BACKGROUND:Veliparib is a potent poly(ADP-ribose) polymerase inhibitor. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of veliparib combined with various FOLFIRI regimens in patients with solid tumours. METHODS:Patients received veliparib (10-270 mg BID, days 1-5, 15-19) and FOLFIRI (days 1-3, 15-17) in three regimens containing 5-fluorouracil 2,400 mg/m2: irinotecan 150 mg/m2 and folinic acid 400 mg/m2 (part 1); irinotecan 180 mg/m2, folinic acid 400 mg/m2, and 5-fluorouracil 400 mg/m2 bolus (part 2), or irinotecan 180 mg/m2 (part 3). The RP2D was further evaluated in safety expansion cohorts. Preliminary antitumour activity was also assessed. RESULTS:Ninety-two patients received ≥1 veliparib dose. MTD was not reached; RP2D was set at 200 mg BID veliparib plus FOLFIRI (without 5-fluorouracil bolus). Most common treatment-emergent adverse events were neutropenia (66.3%), diarrhoea, and nausea (60.9% each). Dose-limiting toxicities (n = 4) were grade 3 gastritis and grade 4 neutropenia and febrile neutropenia. Veliparib exposure was dose-proportional, with no effects on the pharmacokinetics of FOLFIRI components. Fifteen patients had a partial response (objective response rate, 17.6%). CONCLUSIONS:The acceptable safety profile and preliminary antitumour activity of veliparib plus FOLFIRI support further evaluation of this combination.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Berlin J,Ramanathan RK,Strickler JH,Subramaniam DS,Marshall J,Kang YK,Hetman R,Dudley MW,Zeng J,Nickner C,Xiong H,Komarnitsky P,Shepherd SP,Hurwitz H,Lenz HJdoi
10.1038/s41416-018-0003-3subject
Has Abstractpub_date
2018-04-01 00:00:00pages
938-946issue
7eissn
0007-0920issn
1532-1827pii
10.1038/s41416-018-0003-3journal_volume
118pub_type
杂志文章,多中心研究abstract：:Bleomycin is a chemotherapuetic drug used primarily in the treatment of squamous-cell carcinoma, while misonidazole is an effective radiosensitizer and potent cytotoxic agent selectively affecting hypoxic cells. V79 Chinese hamster cells were used to investigate the cytotoxicity of bleomycin (BLM) under aerated and hy...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1978.34
更新日期：1978-02-01 00:00:00
abstract：:Solid tumours are often highly acidic compared to normal tissue, and tumour extracellular acidosis contributes to multiple aspects of cancer progression. Now, Anemone et al. in this issue of the British Journal of Cancer provide in vivo evidence that the degree to which various breast cancer cell lines acidify their e...
journal_title：British journal of cancer
pub_type： 社论
doi：10.1038/s41416-020-01171-2
更新日期：2021-01-01 00:00:00
abstract：:We analysed the molecular genetic profiles of breast cancer samples before and after neoadjuvant chemotherapy with combination doxorubicin and cyclophosphamide (AC). DNA was obtained from microdissected frozen breast core biopsies from 44 patients before chemotherapy. Additional samples were obtained before the second...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603483
更新日期：2007-01-29 00:00:00
abstract：BACKGROUND:Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern ...
journal_title：British journal of cancer
pub_type： 杂志文章,实务指引
doi：10.1038/bjc.2017.334
更新日期：2017-11-07 00:00:00
abstract：:To determine whether resistance to chemoimmunotherapy is acquired during therapy, we investigated the effects of chemotherapeutic agents and anti-tumour polysaccharide, lentinan, on the progression of Rous sarcoma virus-induced S908.D2 fibrosarcomas. The chemoimmunotherapy was effective against the parental S908.D2-be...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.82
更新日期：1996-02-01 00:00:00
abstract：BACKGROUND:Dulanermin (rhApo2L/TRAIL) induces apoptosis by binding to death receptors DR4 and DR5, leading to caspase activation and subsequent cell death. A Phase1a trial evaluated the safety and tolerability of dulanermin in patients with advanced tumours. One aim was to develop and validate pharmacodynamic biomarker...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.456
更新日期：2011-12-06 00:00:00
abstract：:In 101 breast cancer patients, measurement of oestrogen receptor status in multiple biopsies across a tumour reveals a highly significant difference in the proportion of patients remaining either disease-free (P less than 0.04) or alive (P less than 0.005), when those with uniformly receptor positive (++) primary tumo...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.129
更新日期：1989-04-01 00:00:00
abstract：:The relationship between skin tumours in man and exposure to polyaromatic hydrocarbons has been studied in lathe operators exposed to cutting oils. Seven cases of scrotal cancer and 13 cases of senile keratosis and keratoacanthoma were observed. The risk varied as the 1.6th power of duration of exposure for cancer on ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1990.435
更新日期：1990-12-01 00:00:00
abstract：:Alcohol consumption has been inconsistently associated with breast cancer risk. Recent studies suggest that genetic polymorphisms of glutathione S-transferases (GSTs) may modify this relation. To determine if breast cancer risk is associated with GSTM1 and GSTT1 genetic polymorphisms, and to evaluate the effect modifi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600708
更新日期：2003-01-13 00:00:00
abstract：:The tissue-specific translation elongation factor eEF1A2 is a potential oncogene that is overexpressed in human ovarian cancer. eEF1A2 is highly similar (98%) to the near-ubiquitously expressed eEF1A1 (formerly known as EF1-alpha) making analysis with commercial antibodies difficult. We wanted to establish the express...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603748
更新日期：2007-05-21 00:00:00
abstract：:The structural characteristics of mesoionic compounds, which contain distinct regions of positive and negative charges associated with a poly-heteroatomic system, enable them to cross cellular membranes and interact strongly with biomolecules. Potential biological applications have been described for mesoionic compoun...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601946
更新日期：2004-07-19 00:00:00
abstract：BACKGROUND:The role of melanoma inhibitory activity 2 (MIA2) was examined in human oral squamous cell carcinoma (OSCC). METHODS:MIA2 role was examined by immunohistochemistry of human OSCCs and knockdown studies using human 3 OSCC cell lines with MIA2 expression. RESULTS:MIA2 expression was observed in 62 (66.7%) of ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.27
更新日期：2013-04-16 00:00:00
abstract：:Telomerase, an enzyme related with cellular immortality, has been extensively studied in many kinds of malignant tumours for clinical diagnostic or prognostic utilities. Telomerase activity is mainly regulated by the expression of hTERT (human telomerase reverse transcriptase), which is a catalytic component of human ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602054
更新日期：2004-08-31 00:00:00
abstract：BACKGROUND:Non-invasive biomarkers of disease progression in mice with cancer are lacking making it challenging to implement appropriate humane end points. We investigated whether body temperature, food and water consumption could be used to predict tumour burden. METHODS:Thirty-six male, wild-type C57Bl/6 mice were i...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.818
更新日期：2014-02-18 00:00:00
abstract：:A total of 152 non-small cell lung cancers (NSCLC) were studied retrospectively to determine the relationship between epidermal growth factor receptor (EGF-R) status and the histological type, tumour size, nodal status and prognosis. EGF-R status was assessed on routinely embedded paraffin sections with an antibody to...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.156
更新日期：1989-05-01 00:00:00
abstract：:Monoclonal antibodies 19-9 and C-50 were used to assay the cancer associated tumour antigens CA 19-9 and CA-50 in plasma from patients with confirmed pancreatic cancer, and related to the blood group and Lewis blood cell status. The plasma expressions of CA 19-9 or CA-50 were similar, including cases where the patient...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1990.241
更新日期：1990-07-01 00:00:00
abstract：:NRH:Quinone Oxidoreductase 2 (NQO2) has been described as having no enzymatic activity with nicotinamide adenine dinucleotide (NADH) or NADPH as electron donating cosubstrates. Mitomycin C (MMC) is both a substrate for and a mechanistic inhibitor of the NQO2 homologue NQO1. NRH:quinone oxidoreductase 2 catalysed the r...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603414
更新日期：2006-11-06 00:00:00
abstract：BACKGROUND:We performed a retrospective nationwide study to explore age as a prognostic factor in synovial sarcoma patients. METHODS:Data on 613 synovial sarcoma patients were obtained from the Netherlands Cancer Registry. The prognostic relevance of age groups (children, adolescent and young adults (AYAs), adults, an...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2015.375
更新日期：2015-12-01 00:00:00
abstract：:In resection tissue samples of colorectal carcinomas, the concentration of urokinase-type plasminogen activator (u-Pa) was found to be significantly higher than in the normal parent mucosal tissue, while there was less tissue-type plasminogen activator (t-PA). u-PA and t-PA were also determined in endoscopic biopsies ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.293
更新日期：1989-09-01 00:00:00
abstract：:Accumulating evidence suggests that the p53 gene is a good target for molecular epidemiological studies. We previously reported an association between the presence of p53 mutations and lifetime cigarette consumption. Although over 675 p53 mutations have been reported in lung cancers in the literature thus far, very li...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.258
更新日期：1998-05-01 00:00:00
abstract：:A prospective, consecutive study of the aetiology of treatment-associated diarrhoea was conducted in 25 patients with disseminated germ cell cancer treated with intensive chemotherapy. Clostridium difficile was isolated in 45% of the diarrhoea episodes, which makes this species the most important bacterial pathogen in...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.334
更新日期：1992-10-01 00:00:00
abstract：:Ultrafiltrates from spleen inhibited both DNA synthesis and the proliferation of normal lymphocytes stimulated inculture from both mouse and man without apparent cytotoxicity. However, the same doses of this spleen ultrafiltrate will kill up to two-thirds of the leukaemic lymphoblasts from both mouse and man after 24 ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1975.280
更新日期：1975-12-01 00:00:00
abstract：:The antiapoptotic Livin/ML-IAP gene has recently gained much attention as a potential new target for cancer therapy. Reports indicating that livin is expressed almost exclusively in tumours, but not in the corresponding normal tissue, suggested that the targeted inhibition of livin may present a novel tumour-specific ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604028
更新日期：2007-11-05 00:00:00
abstract：:Exposure to the fibrous mineral erionite is known to induce mesothelioma in man and laboratory animals. Previous studies demonstrated the presence of a trypsin-like protease associated with tumour cells. This protease could be demonstrated by the use of fluorescent probes which located cells possessing this enzyme. We...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.269
更新日期：1988-11-01 00:00:00
abstract：:For stage III non-small cell lung cancer (NSCLC), approximately a third of patients survive up to 5 years, with decreasing 5-year survival rates for stage IIIB and stage IIIC disease. Although curable, stage III NSCLC encompasses a diverse range of disease presentation, with an equally complex range of multi-modal tre...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/s41416-020-01069-z
更新日期：2020-12-01 00:00:00
abstract：:A study is presented of all cases of primary sarcoma of bone registered during the period 1946 to 1974 for a specified population resident in south-western England. Ninety-six per cent of the 365 cases were histologically and radiologically verified and are separated into 8 categories of sarcoma. The number of tumours...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1977.221
更新日期：1977-10-01 00:00:00
abstract：:Benzo[b]thiophenesulphonamide 1,1-dioxide (BTS) derivatives are strong cytotoxic agents that induce reactive oxygen species (ROS) overproduction and apoptosis in tumour cells. Although the precise origin of BTS-induced ROS is not known, a clear correlation between their cytotoxic effect and ability to inhibit a tumour...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602383
更新日期：2005-02-28 00:00:00
abstract：:A retrospective case-control study of 200 patients with head and neck cancer, and 200 controls matched for age and sex, confirmed the importance of tobacco and alcohol consumption in the aetiology of malignant tumours of the upper gastrointestinal and upper respiratory tracts. A male-female ratio of 3:1 was found, and...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.26
更新日期：1981-02-01 00:00:00
abstract：BACKGROUND:Malignancy alters cellular complex lipid metabolism and membrane lipid composition and turnover. Here, we investigated whether tumorigenesis in cancer-derived prostate epithelial cell lines influences protein kinase C-linked turnover of ethanolamine phosphoglycerides (EtnPGs) and alters the pattern of ethano...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.457
更新日期：2014-10-14 00:00:00
abstract：:The author Sara Lonardi was incorrectly listed as Sara Leonardi. The correct name is listed above. ...
journal_title：British journal of cancer
pub_type： 杂志文章,已发布勘误
doi：10.1038/s41416-018-0067-0
更新日期：2018-06-01 00:00:00
