Abstract:
:Cetuximab in combination with an irinotecan-containing regimen is a standard treatment in patients with KRAS wild-type (KRAS WT), metastatic colorectal cancer (mCRC). We investigated the addition of the oral MET inhibitor tivantinib to cetuximab + irinotecan (CETIRI) based on preclinical evidence that activation of the MET pathway may confer resistance to anti-EGFR therapy. Previously treated patients with KRAS WT advanced or mCRC were enrolled. The phase 1, open-label 3 + 3, dose-escalation study evaluated the safety and maximally tolerated dose of tivantinib plus CETIRI. The phase 2, randomized, double-blinded, placebo-controlled study of biweekly CETIRI plus tivantinib or placebo was restricted to patients who had received only one prior line of chemotherapy. The phase 2 primary endpoint was progression-free survival (PFS). The recommended phase 2 dose was tivantinib (360 mg/m(2) twice daily) with biweekly cetuximab (500 mg/m(2)) and irinotecan (180 mg/m(2)). Among 117 patients evaluable for phase 2 analysis, no statistically significant PFS difference was observed: 8.3 months on tivantinib vs. 7.3 months on placebo (HR, 0.85; 95% confidence interval, 0.55-1.33; P = 0.38). Subgroup analyses trended in favor of tivantinib in patients with MET-High tumors by immunohistochemistry, PTEN-Low tumors, or those pretreated with oxaliplatin, but subgroups were too small to draw conclusions. Neutropenia, diarrhea, nausea and rash were the most frequent severe adverse events in tivantinib-treated patients. The combination of tivantinib and CETIRI was well tolerated but did not significantly improve PFS in previously treated KRAS WT mCRC. Tivantinib may be more active in specific subgroups.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Eng C,Bessudo A,Hart LL,Severtsev A,Gladkov O,Müller L,Kopp MV,Vladimirov V,Langdon R,Kotiv B,Barni S,Hsu C,Bolotin E,von Roemeling R,Schwartz B,Bendell JCdoi
10.1002/ijc.30049subject
Has Abstractpub_date
2016-07-01 00:00:00pages
177-86issue
1eissn
0020-7136issn
1097-0215journal_volume
139pub_type
杂志文章,随机对照试验abstract::Thirty-one different long-term established human carcinoma culture cell lines were examined for the presence or absence of receptors for the Fc portion of immunoglobulin G (IgG) ("Fc receptors"), the third component of complement (C3 receptors), sheep erythrocytes and mouse erythrocytes. Included in the catalogue of l...
journal_title:International journal of cancer
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abstract::The aim of this study was to assess the diagnostic performance of breast imaging in the diagnosis of breast cancer in a non-screening population. In a consecutive set of patients referred for mammography in one year, the results of palpation and radiological breast imaging were scored on a 5-point grading scale and li...
journal_title:International journal of cancer
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abstract::A hamster lymphoid cell line, HCT-2, transformed by human T-cell leukemia virus type I (HTLV-I) was serially transplanted for 9 passages in newborn hamsters. A total of 34 newborn hamsters inoculated intraperitoneally (i.p.) with 0.2-2 X 10(7) HCT-2 cells developed fatal lymphomas with dissemination to various organs ...
journal_title:International journal of cancer
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doi:10.1002/ijc.2910410617
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abstract::Early detection, clinical management and disease recurrence monitoring are critical areas in cancer treatment in which specific biomarker panels are likely to be very important in each of these key areas. We have previously demonstrated that levels of alpha-2-heremans-schmid-glycoprotein (AHSG), complement component C...
journal_title:International journal of cancer
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abstract::Liquid-based cytology (LBC) has replaced conventional cytology (CC) for cervical cancer screening in some countries. However, it remains unclear whether LBC is superior to CC. A randomized controlled trial was conducted between August 2007 and March 2009 in Germany to compare LBC, alone and in combination with compute...
journal_title:International journal of cancer
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更新日期:2013-06-15 00:00:00
abstract::One hundred patients with Ph1-chromosome-positive chronic myelogenous leukemia (CML) with t(9;22) are included in the present investigation. The position of the Ph1 chromosome in relation to the normal as well as the abnormal chromosomes 9 was localized at metaphase in 1,000 bone-marrow cells. Our study suggests that ...
journal_title:International journal of cancer
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abstract::A single treatment of chick embryo fibroblasts with DNA recovered from chick embryo fibroblasts productively infected and transformed with four different strains of RSV, or productively infected with two different strains of RAV, resulted in virus production and cell transformation (in the case of RSV) two or three p...
journal_title:International journal of cancer
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abstract::Vascular endothelial growth factor (VEGF) is an angiogenic factor that also functions as an autocrine growth factor for VEGF receptor (VEGFR)-2(+) melanomas. In multiple studies, VEGFR-2 was detected by immunostaining in 78-89% of human melanoma cells, suggesting that most patients with melanoma would benefit from an...
journal_title:International journal of cancer
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abstract::Data from a hospital-based matched case-control study with 531 male pairs were analyzed for risks of cancer of the lower urinary tract associated with previous employment and particular occupational exposures. Statistically significant odds ratios were obtained for ever-employment as mining workers (2.0), turners (2.3...
journal_title:International journal of cancer
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abstract::We have shown that modulation of intracellular calcium in EBV latently infected cells could induce the expression of viral antigens, and suggested that a protein kinase-C (PKC) may play a major role in the EBV genome activation. We now report further investigations on the role of PKC using 2 selective enzymatic inhibi...
journal_title:International journal of cancer
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doi:10.1002/ijc.2910400624
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abstract::Detection of methylated free-circulating DNA (mfcDNA) for hyperplastic polyposis 1 (HPP1) in blood is correlated with a poor prognosis for patients with metastatic colorectal cancers (mCRC). Here, we analyzed the plasma levels of HPP1 mfcDNA in mCRC patients treated with a combination therapy containing a fluoropyrimi...
journal_title:International journal of cancer
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更新日期:2017-05-01 00:00:00
abstract::A case of epidermodysplasia verruciformis in a patient from Upper-Volta is described. Slightly elevated, flat warts were observed on hands, feet, arms and legs, and pityriasis versicolor-like lesions were found mainly on the trunk. The patient showed no malignant tumors. Histological examination revealed hyperkeratosi...
journal_title:International journal of cancer
pub_type: 杂志文章
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journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:2013-09-15 00:00:00
abstract::HtrA1, a member of serine protease family, has been previously found to be involved in resistance to chemotherapy in ovarian cancer although the underlying mechanism is not clear. Using mixture-based oriented peptide library approach, previously we identified X-linked inhibitor of apoptosis protein (XIAP), a member of...
journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:2012-03-01 00:00:00
abstract::There is limited research on the effect of dietary quality on hepatocellular carcinoma (HCC) risk in populations with relatively high risk of HCC. Using data from Singapore Chinese Health Study, a prospective cohort study, of 63 257 Chinese aged 45 to 74, we assessed four diet-quality index (DQI) scores: the Alternati...
journal_title:International journal of cancer
pub_type: 杂志文章
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journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:2000-04-01 00:00:00
abstract::Sunlight is essential for the production of vitamin D in the body. Evidence exists to suggest that vitamin D metabolites may have a role in tumor growth suppression. In this large study, involving over a million cancer patients from the United Kingdom, we have analyzed the role of season of diagnosis and sunlight expo...
journal_title:International journal of cancer
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更新日期:2006-10-01 00:00:00
abstract::Multiple genetic changes occur during the evolution of normal cells into cancer cells. It has been reported that both cyclin D1 and p53 genes play major roles in oncogenesis and/or cell cycle control in various cancers. In this study, we examined the overexpression of cyclin D1 and p53 by the immunohistochemical metho...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970620)74:3<310::aid-ijc
更新日期:1997-06-20 00:00:00
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abstract::Biopsies obtained from 74 Tunisian women with breast cancer (33 cases), benign breast disease (17 cases), and cervical cancer (24 cases) were assayed for the presence of an antigen cross-reacting with gp52 of the mouse mammary tumor virus (MMTV) in order to determine the frequency and possible prognostic significance ...
journal_title:International journal of cancer
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abstract::Cryopreserved tumour cells obtained from the ascitic fluid of a patient with an ovarian carcinoma were employed to determine the effect on in vitro drug cytotoxicities of varying both drug concentration and exposure time. Four antitumour drugs, in common clinical usage, were selected for study. Tumour-cell survival fo...
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journal_title:International journal of cancer
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更新日期:1998-05-18 00:00:00
abstract::Family history of urogenital cancers has been associated with an increased risk of cancer at the same sites. To evaluate the risks of bladder, prostate and renal cell neoplasms for family history of urogenital cancers in first-degree relatives, we analysed data from a case-control study conducted in northern Italy bet...
journal_title:International journal of cancer
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abstract::More women are surviving after breast cancer due to early detection and modern treatment strategies. Body weight also influences survival. We aimed to characterize associations between postdiagnosis weight change and prognosis in postmenopausal long-term breast cancer survivors. We used data from a prospective populat...
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journal_title:International journal of cancer
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abstract::During natural metastasis, cancer cells are released continuously into the bloodstream and arrested in target organs; the process is repetitive rather than a single event. In this communication, the effect of preceding on successive "pulses" of cancer cells is discussed in relation to the arrest, retention and tumor f...
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abstract::The U.S. Preventive Services Task Force (USPSTF) recently updated their national lung screening guidelines and recommended low-dose computed tomography (LDCT) for lung cancer (LC) screening through age 80. However, the risk of overdiagnosis among older populations is a concern. Using four comparative models from the C...
journal_title:International journal of cancer
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abstract::Human papillomavirus (HPV) is detected in nearly all cervical cancers and approximately half of vaginal cancers. However, vaginal cancer is an order of magnitude less common than cervical cancer, not only in the general population but also among women with HIV/AIDS. It is interesting therefore that recent studies foun...
journal_title:International journal of cancer
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abstract::The recently identified cell adhesion regulator (CAR) modulates the process of integrin-mediated cell adhesion. The CAR gene is located on 16q, a locus at which high levels of allelic losses have been demonstrated in advanced human hepatocellular carcinoma (HCC). We studied the possible involvement of the CAR gene in ...
journal_title:International journal of cancer
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abstract::Obesity has been postulated to increase the risk of colorectal cancer by mechanisms involving insulin resistance and the metabolic syndrome. We examined the associations of body mass index (BMI), waist circumference, the metabolic syndrome, metabolic obesity phenotypes and homeostasis model-insulin resistance (HOMA-IR...
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