Phase II study of pazopanib monotherapy in metastatic gastroenteropancreatic neuroendocrine tumours.

Abstract:

BACKGROUND:Treatment options for patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs) are still limited. We investigated the antitumour activity and safety profile of pazopanib--a multitarget drug with anti-angiogenic activity in patients with metastatic GEP NETs. METHODS:This was a nonrandomised, open-labeled, single-center phase II study. Pazopanib was orally administered at a dose of 800 mg daily continuously with a 28-day cycle. The primary end point was an objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST). The secondary end points were progression-free survival (PFS), overall survival (OS) and safety. An independent review of objective response was planned. The trial is registered with ClinicalTrials.gov, NCT number 01099540. Correlative biomarker analyses were performed. RESULTS:Between April 2010 and February 2012, a total of 37 patients were enrolled. Thirty-two percent of the enrolled patients had pancreatic primary and 22% of the patients had colorectal primary NETs. This phase II study demonstrated an objective response rate of 18.9% (7 of the 37, 95% CI 8.0-35.2) and a disease control rate (CR+confirmed PR+stable disease) of 75.7% (28 of the 37, 95% CI, 58.8-88.2) in metastatic GEP NETs. The independent review demonstrated a higher overall response rate of 24.3% (95% CI, 11.8-41.2%) with nine confirmed PRs. CONCLUSION:Pazopanib showed a comparable efficacy to other targeted agents not only in pancreatic NETs but also in NETs originating from gastrointestinal (GI) tract.

journal_name

Br J Cancer

authors

Ahn HK,Choi JY,Kim KM,Kim H,Choi SH,Park SH,Park JO,Lim HY,Kang WK,Lee J,Park YS

doi

10.1038/bjc.2013.470

subject

Has Abstract

pub_date

2013-09-17 00:00:00

pages

1414-9

issue

6

eissn

0007-0920

issn

1532-1827

pii

bjc2013470

journal_volume

109

pub_type

杂志文章
  • The relationship between the presence and site of cancer, an inflammation-based prognostic score and biochemical parameters. Initial results of the Glasgow Inflammation Outcome Study.

    abstract:BACKGROUND:Cancer incidence is increasing in the United Kingdom, as well as on a global basis. Biochemical parameters, such as C-reactive protein and albumin (combined to form the modified Glasgow Prognostic Score, mGPS), alkaline phosphatase (Alk phos), gamma-glutamyl transferase (GGT) and serum calcium have been repo...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6605855

    authors: Proctor MJ,Talwar D,Balmar SM,O'Reilly DS,Foulis AK,Horgan PG,Morrison DS,McMillan DC

    更新日期:2010-09-07 00:00:00

  • High prevalence of Clostridium difficile diarrhoea during intensive chemotherapy for disseminated germ cell cancer.

    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

    authors: Nielsen H,Daugaard G,Tvede M,Bruun B

    更新日期:1992-10-01 00:00:00

  • Role of beta3-adrenergic receptors in the action of a tumour lipid mobilizing factor.

    abstract::Induction of lipolysis in murine white adipocytes, and stimulation of adenylate cyclase in adipocyte plasma membranes, by a tumour-produced lipid mobilizing factor, was attenuated by low concentrations (10(-7)--10(-5)M) of the specific beta3-adrenoceptor antagonist SR59230A. Lipid mobilizing factor (250 nM) produced c...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6600086

    authors: Russell ST,Hirai K,Tisdale MJ

    更新日期:2002-02-01 00:00:00

  • The effect of family size on estimates of the frequency of hereditary non-polyposis colorectal cancer.

    abstract::Diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is currently based on phenotypical analysis of an expanded pedigree. Diagnostic guidelines ('Amsterdam criteria') proposed by the International Collaborative Group on HNPCC are often too stringent for use with small families. There is also the possibility...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1995.508

    authors: Percesepe A,Anti M,Roncucci L,Armelao F,Marra G,Pahor M,Coco C,Gasbarrini G,Ponz de Leon M

    更新日期:1995-11-01 00:00:00

  • The effect of Corynebacterium parvum therapy on immunoglobulin class and IgG subclass levels in cancer patients.

    abstract::Detailed serological studies have been undertaken in a small group of cancer patients receiving nonspecific immunotherapy with Corynebacterium parvum (C. parvum). These patients included 4 cases of recurrent malignant melanoma, 2 of stomach cancer and 2 of recurrent breast cancer. They all received an initial i.v. inf...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1975.229

    authors: James K,Clunie GJ,Woodruff MF,McBride WH,Stimson WH,Drew R,Catty D

    更新日期:1975-09-01 00:00:00

  • Activation and activities of the p53 tumour suppressor protein.

    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

    authors: Bálint E E,Vousden KH

    更新日期:2001-12-14 00:00:00

  • Co-detection of members of the urokinase plasminogen activator system in tumour tissue and serum correlates with a poor prognosis for soft-tissue sarcoma patients.

    abstract:BACKGROUND:The urokinase plasminogen activator (uPA) system is one of the best-investigated protease systems, both under physiological and pathological conditions, including various types of cancer. However, effects of co-expression of members of the uPA system in soft-tissue sarcoma (STS) patients at the protein level...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6605520

    authors: Taubert H,Würl P,Greither T,Kappler M,Bache M,Lautenschläger C,Füssel S,Meye A,Eckert AW,Holzhausen HJ,Magdolen V,Kotzsch M

    更新日期:2010-02-16 00:00:00

  • Continued inadequacies in data sources for the evaluation of cancer services.

    abstract::There is a need to evaluate cancer services and provide a baseline on current treatment success and organization. This study shows that this process may be severely hindered by case note destruction or inaccessibility and incomplete information. This is an ongoing problem that needs to be addressed now. ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1997.21

    authors: Smith SJ,Muir KR,Wolstenholme JL,Thornhill KG,Zamorski A,Tolley K,Logan RF,Chilvers CE

    更新日期:1997-01-01 00:00:00

  • Prognostic value of preoperative serum CEA level compared to clinical staging. I. Colorectal carcinoma.

    abstract::In a clinical investigation of observed postoperative survival, 563 patients have been registered for primary surgical treatment of colorectal cancer since 1974. The potential prognostic factors examined within the first days of hospitalization for primary resection included age of the patients, operability, location ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1981.250

    authors: Staab HJ,Anderer FA,Brümmendorf T,Stumpf E,Fischer R

    更新日期:1981-11-01 00:00:00

  • Comparison of prognostic factors in patients in phase I trials of cytotoxic drugs vs new noncytotoxic agents.

    abstract::The aims of this study were to identify prognostic variables for toxicity and survival in patients with cancer participating in phase I clinical trials and compare characteristics of those treated with cytotoxic chemotherapy (CT) and non-cytotoxic drugs (non-CT). Data were collected from 420 (114 CT, 306 non-CT) patie...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6601218

    authors: Han C,Braybrooke JP,Deplanque G,Taylor M,Mackintosh D,Kaur K,Samouri K,Ganesan TS,Harris AL,Talbot DC

    更新日期:2003-10-06 00:00:00

  • Induction of myogenic differentiation in human rhabdomyosarcoma cells by ionising radiation, N,N-dimethylformamide and their combination.

    abstract::Differentiation-inducing ability of gamma-radiation, N,N-dimethylformamide and their combination has been tested on human rhabdomyosarcoma RMZ-RC2 clone cells. Ionising radiation at 2-5 Gy doses induced a more differentiated morphology, with the appearance of an increased proportion of multinuclear myotube-like cells,...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1992.107

    authors: Nicoletti G,De Giovanni C,Landuzzi L,Simone G,Rocchi P,Nanni P,Lollini PL

    更新日期:1992-04-01 00:00:00

  • Oncolytic activity of Sindbis virus in human oral squamous carcinoma cells.

    abstract:BACKGROUND:Sindbis virus (SIN) infection causes no or only mild symptoms (fever, rash, and arthralgia) in humans. However, SIN has a strong cytopathic effect (CPE) on various cancer cells. This study focuses on the oncolytic activity of SIN AR399 on oral cancer cells compared with reovirus, a well-known oncolytic virus...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6605209

    authors: Saito K,Uzawa K,Kasamatsu A,Shinozuka K,Sakuma K,Yamatoji M,Shiiba M,Shino Y,Shirasawa H,Tanzawa H

    更新日期:2009-08-18 00:00:00

  • Cell-cell contact affects cellular sensitivity to hyperthermia.

    abstract::The influence on heat sensitivity of interactions between HT29 human colon adenocarcinoma cells grown in two- or three-dimensional contact was investigated. No evidence for intercellular cooperation affecting cellular sensitivity to hyperthermia was found. Cells grown in monolayer were found to be more heat sensitive ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1985.268

    authors: Dobrucki J,Bleehen NM

    更新日期:1985-12-01 00:00:00

  • Human primary brain tumour metabolism in vivo: a phosphorus magnetic resonance spectroscopy study.

    abstract::Magnetic resonance spectroscopy was used to study intracellular pH and compounds which contain phosphorus in normal human brain and primary brain tumours non-invasively. In normal subjects (n = 7) intracellular pH (pHi) of the brain was 7.03 +/- 0.02 (mean +/- s.e.m.). The pHi did not vary between superficial (2 cm, m...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1989.300

    authors: Cadoux-Hudson TA,Blackledge MJ,Rajagopalan B,Taylor DJ,Radda GK

    更新日期:1989-09-01 00:00:00

  • Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers.

    abstract::We have previously reported that supplementation with folic acid (1.2 mg day(-1) for 12 week) elicited a significant improvement in the folate status of 61 healthy volunteers. We have examined effects of this supplement on markers of genomic stability. Little is known about the effect of folate supplementation on DNA ...

    journal_title:British journal of cancer

    pub_type: 杂志文章,随机对照试验

    doi:10.1038/sj.bjc.6603197

    authors: Basten GP,Duthie SJ,Pirie L,Vaughan N,Hill MH,Powers HJ

    更新日期:2006-06-19 00:00:00

  • Deletion mapping on chromosome 10q25-q26 in human endometrial cancer.

    abstract::To understand genetic events which play a role in the development and/or progression of human endometrial cancer, we studied allelotypes on all autosomal chromosomes, as well as chromosome X, with 42 microsatellite markers and 56 endometrial cancers. The most frequent loss of heterozygosity (LOH) was observed on the l...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1996.663

    authors: Nagase S,Sato S,Tezuka F,Wada Y,Yajima A,Horii A

    更新日期:1996-12-01 00:00:00

  • The monolayer and organ culture of human colorectal carcinomata and the associated "normal" colonic mucosa and their production of carcinoembryonic antigens.

    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

    authors: Breborowicz J,Easty GC,Birbeck M,Robertson D,Nery R,Neville AM

    更新日期:1975-05-01 00:00:00

  • Vascular function and the probability of skin necrosis after photodynamic therapy: an experimental study.

    abstract::The clearance of an intradermally-injected solution of 133Xenon in 0.9% saline has been used to study the impairment and recovery of blood flow in mouse tail for 5 days following photodynamic therapy (PDT) with 2mg TPPS i.v. per mouse and a range of doses of white light. Impairment of blood flow was observed within 10...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1988.105

    authors: Benstead K,Moore JV

    更新日期:1988-05-01 00:00:00

  • Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer.

    abstract:BACKGROUND:The host immune reaction is represented by immune/inflammatory cell infiltrates. Here we systematically analysed tumour-infiltrating immune/inflammatory cells in pancreatic ductal carcinoma (PDC) and evaluated their clinicopathological impact. METHODS:Using immunohistochemistry, we examined tumour-infiltrat...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.2013.32

    authors: Ino Y,Yamazaki-Itoh R,Shimada K,Iwasaki M,Kosuge T,Kanai Y,Hiraoka N

    更新日期:2013-03-05 00:00:00

  • Restored T-cell activation mechanisms in human tumour-infiltrating lymphocytes from melanomas and colorectal carcinomas after exposure to interleukin-2.

    abstract::We investigated the effects of interleukin-2 (IL-2) exposure on T-cell signal transduction molecules and apoptosis markers in tumour-infiltrating lymphocytes (TIL) isolated from 20 melanoma and 16 colorectal carcinoma metastases and expanded in vitro for therapeutic reinfusion. Before IL-2 culture, TIL showed undetect...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6600679

    authors: De Paola F,Ridolfi R,Riccobon A,Flamini E,Barzanti F,Granato AM,Mordenti GL,Medri L,Vitali P,Amadori D

    更新日期:2003-01-27 00:00:00

  • Cytosolic phospholipase A2-α expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours.

    abstract:BACKGROUND:The eicosanoid signalling pathway promotes the progression of malignancies through the production of proliferative prostaglandins (PGs). Cytosolic phospholipase A(2)α (cPLA(2)α) activity provides the substrate for cyclooxygenase-dependent PG release, and we have previously found that cPLA(2)α expression corr...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6606025

    authors: Caiazza F,McCarthy NS,Young L,Hill AD,Harvey BJ,Thomas W

    更新日期:2011-01-18 00:00:00

  • Metabolism of the broad-spectrum neuropeptide growth factor antagonist: [D-Arg1, D-Phe5, D-Trp7,9, Leu11]-substance P.

    abstract::Broad-spectrum neuropeptide growth factor antagonists, such as [D-Arg1, D-Phe5, D-Trp7,9, Leu11]substance P (antagonist D) and [Arg6, D-Trp7,9, NmePhe8]substance P(6-11) (antagonist G), are currently being investigated as possible anti-tumour agents. These compounds are hoped to be effective against neuropeptide-drive...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1996.126

    authors: Jones DA,Cummings J,Langdon SP,Maclellan AJ,Higgins T,Rozengurt E,Smyth JF

    更新日期:1996-03-01 00:00:00

  • Effect of active immunization with irradiated tumour cells on specific serum inhibitors of cell-mediated immunity in patients with disseminated cancer.

    abstract::The sera from patients with advanced cancer were tested for their specific inhibitory effects on the cytotoxicity of autologous lymphocytes on tumour cells in a microculture assay. By adding a standard volume of the sera to suspensions of well-washed lymphocytes the inhibitory effect was quantitated by comparison with...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1973.67

    authors: Currie GA

    更新日期:1973-07-01 00:00:00

  • Met/HGF receptor modulates bcl-w expression and inhibits apoptosis in human colorectal cancers.

    abstract::The met proto-oncogene is the tyrosine kinase growth factor receptor for hepatocyte growth factor. In the present study, we investigated the role of met expression on the modulation of apoptosis in colorectal tumours. The gene expressions of c-met and the anti-apoptotic bcl-2 family, including bcl-2, bcl-x(L)and bcl-w...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1054/bjoc.2000.1301

    authors: Kitamura S,Kondo S,Shinomura Y,Kanayama S,Miyazaki Y,Kiyohara T,Hiraoka S,Matsuzawa Y

    更新日期:2000-09-01 00:00:00

  • Cyclin A is associated with an unfavourable outcome in patients with non-small-cell lung carcinomas.

    abstract::Specimens of formalin-fixed, paraffin-embedded non-small-cell lung carcinomas (NSCLCs; n = 187) were analysed immunohistochemically for expression of cyclin A. The analysis was intended to determine whether cyclin A has additional prognostic value for predicting patients' survival and drug response. Of the 187 NSCLCs,...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1997.302

    authors: Volm M,Koomägi R,Mattern J,Stammler G

    更新日期:1997-01-01 00:00:00

  • Study populations for period analyses of cancer survival.

    abstract:BACKGROUND:Period analysis is increasingly used to compute long-term cancer survival, as it provides better prediction of survival of newly diagnosed patients than traditional cohort analysis. However, the patient population to which period survival estimates best pertain to and which should be described in a study is ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.2013.14

    authors: Jansen L,Hakulinen T,Brenner H

    更新日期:2013-02-19 00:00:00

  • Endometrial cancer risk factors among Lynch syndrome women: a retrospective cohort study.

    abstract:BACKGROUND:Lynch syndrome (LS) is associated with a significant lifetime risk of endometrial cancer (EC). There are limited data on factors modifying the EC risk in LS patients. METHODS:The study cohort included 136 LS mutation-positive women. Exposure data were collected by postal questionnaires. Cox regression model...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.2016.193

    authors: Staff S,Aaltonen M,Huhtala H,Pylvänäinen K,Mecklin JP,Mäenpää J

    更新日期:2016-07-26 00:00:00

  • Antibody guided lymphangiography in the staging of cervical cancer.

    abstract::Iodine-123-labelled tumour associated monoclonal antibody HMFG2 was administered intralymphatically at a time that cannulation of pedal lymphatic vessels was performed for standard lymphangiography in 6 patients with cervical cancer. Gamma camera images were taken at 2 h and 24 h after injection of antibody and at a s...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1985.125

    authors: Epenetos AA

    更新日期:1985-06-01 00:00:00

  • Educational attainment among survivors of childhood cancer: a population-based cohort study in Denmark.

    abstract::We identified 2384 patients in the Danish Cancer Register in whom cancer had been diagnosed in 1960-1996 before they reached the age of 20 and compared them with 53 143 sex- and age-matched controls identified from the Register of Population Statistics. Complete education records and demographic and socioeconomic info...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6602085

    authors: Koch SV,Kejs AM,Engholm G,Johansen C,Schmiegelow K

    更新日期:2004-08-31 00:00:00

  • Raman spectroscopy: elucidation of biochemical changes in carcinogenesis of oesophagus.

    abstract::Several techniques are under development to diagnose oesophageal adenocarcinoma at an earlier stage. We have demonstrated the potential of Raman spectroscopy, an optical diagnostic technique, for the identification and classification of malignant changes. However, there is no clear recognition of the biochemical chang...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6603102

    authors: Shetty G,Kendall C,Shepherd N,Stone N,Barr H

    更新日期:2006-05-22 00:00:00