Abstract:
BACKGROUND:Sunitinib (S) is a multi-targeted tyrosine kinase inhibitor. It is synergistic with chemotherapy in preclinical models. We hypothesized that sunitinib in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) would be a tolerable and effective regimen in advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. OBJECTIVE:Since the outcomes of advanced gastric and GEJ adenocarcinoma patients are poor, we decided to study a combination of FOLFIRI + S, to establish tolerability and efficacy. PATIENTS AND METHODS:This was a phase I study for patients with advanced chemo-naïve gastric or GEJ adenocarcinoma. Dose escalation used a standard 3 + 3 design. The primary objective was to determine the tolerability and safety of FOLFIRI + S. Secondary objectives were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). RESULTS:A total of 23 patients participated in the study (male 78%, female 22%). The median age was 61 (range: 38-77) years. Median follow-up time was 67.5 (95% CI 58.9-76) months. The most frequently reported adverse events were anemia (78%; G3/4: 4%), neutropenia (78%; G3/4: 43%), nausea (74%; G3/4:13%), diarrhea (65%; G3/4: 4%), vomiting (61%, G3/4: 9%) lymphopenia (52%; G3/4: 13%), and fatigue (52%; G3/4:17%). Two dose-limiting toxicities were noted each at dose level (DL) 1 and 1A, one at DL 1B, and three at DL 2. Maximum tolerated dose was determined at DL 1B. At the time of data reporting, 21 patients had died. The median OS and PFS were 12.4 (95% CI 8.9, 16.5) months and 6.2 (95% CI 3.4, 13.5) months, respectively. Of all patients, 35% (eight out of 23) had a partial response. CONCLUSIONS:FOLFIRI + S has signs of clinical activity in patients with advanced gastric and GEJ adenocarcinoma, and the side-effect profile was similar to previously reported studies. Current treatment paradigms in gastric cancer probably negate further study of this regimen. ClinicalTrials.gov identifier: NCT00524186.
journal_name
Target Oncoljournal_title
Targeted oncologyauthors
Mukherjee S,Fountzilas C,Boland PM,Gosain R,Attwood K,Tan W,Khushalani N,Iyer Rdoi
10.1007/s11523-019-00692-ysubject
Has Abstractpub_date
2020-02-01 00:00:00pages
85-92issue
1eissn
1776-2596issn
1776-260Xpii
10.1007/s11523-019-00692-yjournal_volume
15pub_type
杂志文章abstract::Elderly and poor performance status advanced non-small cell lung cancer (NSCLC) patients often tolerate chemotherapy poorly. Special approaches are needed for these patient populations. Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR), erlotinib and gefitinib, are active agents in the t...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-009-0104-2
更新日期:2009-01-01 00:00:00
abstract::Obinutuzumab (Gazyva®, Gazyvaro®) is a recombinant, monoclonal, humanized and glycoengineered, type II, anti-CD20, IgG1 antibody. It has recently been granted an additional indication for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen. In the...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-017-0485-6
更新日期:2017-04-01 00:00:00
abstract::It is believed that the insulin-like growth factor receptor type 1 (IGF-1R) signaling pathway plays a pivotal role in cancer growth, progression, and resistance to anticancer therapies. Strategies are being developed to block IGF-1R as an anticancer treatment. We reviewed several potential strategies for disrupting th...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-009-0123-z
更新日期:2009-12-01 00:00:00
abstract::In subsets of gastrointestinal stromal tumors (GISTs), mutations of the KIT and PDGFRA receptor tyrosine kinases correlate with tumor prognosis and response to tyrosine kinase inhibitors (TKIs). Determining genotypes in TKI-resistant GISTs is challenging due to the potential risks and limitations of repeated biopsies ...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-015-0361-1
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:Peripheral T-cell lymphoma (PTCL) is associated with poor prognosis, particularly in patients with relapsed/refractory (R/R) disease. Pralatrexate, a folate analogue inhibitor, was the first drug approved to treat R/R PTCL. OBJECTIVE:As the distribution of PTCL subtypes differs between populations and few p...
journal_title:Targeted oncology
pub_type: 杂志文章,多中心研究
doi:10.1007/s11523-019-00630-y
更新日期:2019-04-01 00:00:00
abstract::The First-Line Erbitux in Lung Cancer (FLEX) trial showed that the addition of cetuximab to chemotherapy followed by weekly cetuximab maintenance significantly improved survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC). The phase IIIb NSCLC Erbitux Trial (NEXT) trial (NCT00820755) inv...
journal_title:Targeted oncology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s11523-014-0336-7
更新日期:2015-06-01 00:00:00
abstract::Atezolizumab (Tecentriq®), a humanized, anti-programmed cell death ligand-1 (PD-L1) monoclonal antibody, in combination with bevacizumab, carboplatin and paclitaxel (ABCP) or with carboplatin and nab-paclitaxel (ACnP) has been approved as first-line treatment for metastatic nonsquamous NSCLC, based on results from the...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-019-00686-w
更新日期:2019-12-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer diagnosed worldwide. HCC occurs due to chronic liver disease and is often diagnosed at advanced stages. Chemotherapeutic agents such as doxorubicin are currently used as first-line agents for HCC therapy, but these are non-selective cytotox...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-016-0452-7
更新日期:2017-02-01 00:00:00
abstract::Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Efficacy of this drug was documented in the BR.21 trial showing that adenocarcinoma, female gender, Asian ethnicity and never-smoker status are predictive of clinical response to erlotinib. Retrospective studies documented the same bene...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-010-0163-4
更新日期:2010-12-01 00:00:00
abstract:BACKGROUND:Axitinib, an inhibitor of vascular endothelial growth factor (VEGF) receptors, is approved as second-line treatment for advanced renal cell carcinoma (RCC). Agents targeting the VEGF pathway may induce renal toxicities, which may be influenced by pre-existing renal dysfunction. OBJECTIVE:The objective was t...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-015-0389-2
更新日期:2016-04-01 00:00:00
abstract::ABP 980 was developed as a biosimilar to trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2), that is indicated for the treatment of HER2-positive metastatic breast cancer, early breast cancer (EBC), and metastatic gastric cancer. ABP 980 is approved in the United States, Europ...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-019-00675-z
更新日期:2019-12-01 00:00:00
abstract::Despite recent advances that have been made in the therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC), effective management of bone metastases remains a key goal not yet reached. The receptor tyrosine kinase MET and the vascular endothelial growth factor receptor (VEGFR) seem to play an i...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-015-0412-7
更新日期:2016-08-01 00:00:00
abstract::Dynamic contrast-enhanced ultrasonography (DCE-US) is a new functional technique enabling a quantitative assessment of solid tumor perfusion using raw linear data. DCE-US allows the calculation of parameters as slope of wash-in or area under the curve (AUC) representing, respectively, blood flow or blood volume. Reduc...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-010-0136-7
更新日期:2010-03-01 00:00:00
abstract::Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological entity that may occur in patients receiving anti-vascular endothelial growth factor (VEGF) agents such as bevacizumab and tyrosine kinase inhibitors. Little is known about the characteristics of patients at risk for PRES under anti-VEGF agen...
journal_title:Targeted oncology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s11523-011-0201-x
更新日期:2011-12-01 00:00:00
abstract::Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive malignancy with poor outcome occurring in adolescents and young adults. Therapeutic options for patients with advanced disease are limited. Preclinical studies have shown that VEGFR-2 and VEGFA are overexpressed in DSRCT and that DSRCT xenografts wer...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-012-0251-8
更新日期:2013-09-01 00:00:00
abstract::Differentiated thyroid carcinoma is the most frequent neoplasm of the endocrine system. Although thyroid cancer usually has an excellent prognosis, no therapeutic options are available for patients that develop metastases and are or became resistant to radioiodine therapy. The deeper knowledge of molecular aberrations...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-009-0124-y
更新日期:2009-12-01 00:00:00
abstract::We aimed to assess the prognostic role of pretreatment neutrophilia, lymphocytopenia, and neutrophil to lymphocyte ratio (NLR) in patients treated with vascular endothelial growth factor-tyrosine kinase inhibitors (VEGFR-TKIs) for late relapsing (>5 years) metastatic renal cell carcinoma (mRCC). Data were collected fr...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-014-0356-3
更新日期:2015-12-01 00:00:00
abstract::δ-Catenin is the only member of the p120 catenin (p120ctn) subfamily whose normal pattern of expression is restricted to the brain. Similar to p120ctn, δ-catenin can bind to the juxtamembrane domain of E-cadherin. We examined the expression of δ-catenin, p120ctn, and E-cadherin using immunohistochemistry in 95 cases o...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-013-0269-6
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:The prognosis of patients with advanced pancreatic cancer is dismal, and there is a need for novel and effective treatments. OBJECTIVES:Tο determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a novel gemcitabine (G) and temsirolimus (T) combination (phase I) and estimate the 6-m...
journal_title:Targeted oncology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s11523-018-0605-y
更新日期:2018-12-01 00:00:00
abstract::Chemotherapy represents the mainstay of non-small cell lung cancer (NSCLC) treatment, but response is usually observed in only one out of three patients. Massive efforts have been carried out to identify biomarkers that might help clinicians to choose appropriate drugs, by identifying potentially sensitive subjects an...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-010-0132-y
更新日期:2010-03-01 00:00:00
abstract::The advent of imatinib mesilate, an oral target therapy, has dramatically changed the natural history of gastrointestinal stromal tumours (GISTs). This rare neoplasm has become the paradigm of targeted therapies in solid tumours, also introducing a home-based cure concept in oncology. However, it should be retained th...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-012-0221-1
更新日期:2012-12-01 00:00:00
abstract::Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) catalyze the first rate-limiting step in the oxidative metabolism of compounds containing indole rings, including the transformation of the essential amino acid L-tryptophan to N-formyl-L-kynurenine. Through direct and indirect means, IDO exerts bo...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-017-0547-9
更新日期:2018-04-01 00:00:00
abstract::Sorafenib (Nexavar®) is currently the only systemic agent approved for use in hepatocellular carcinoma (HCC). Its approval was based on the results of the pivotal SHARP and Sorafenib Asia-Pacific (AP) trials in Child-Pugh (CP) class A patients with advanced HCC, which showed significantly longer median overall surviva...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-017-0484-7
更新日期:2017-04-01 00:00:00
abstract:OBJECTIVE:To determine the efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in molecularly selected patients with advanced non-small cell lung cancer (NSCLC), we performed this pooled analysis. METHOD:Randomized trials of EGFR-TKIs as treatment for advanced NSCLC wer...
journal_title:Targeted oncology
pub_type: 杂志文章,meta分析,收录出版
doi:10.1007/s11523-015-0376-7
更新日期:2016-02-01 00:00:00
abstract::The selective BRAF inhibitors vemurafenib and dabrafenib yield high response rates and improved overall survival in patients with BRAF V600E-mutant metastatic melanoma. Treatment traditionally continues until disease progression or the development of unacceptable toxicity. Acquired drug resistance and toxicity are key...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-015-0410-9
更新日期:2016-08-01 00:00:00
abstract:BACKGROUND:Immune checkpoint inhibitors (ICIs) demonstrated improved overall survival (OS) in heavily pretreated unselected patients with metastatic gastro-esophageal junction (mGOJ)/gastric cancer (GC). Attempts to select patients based on programmed death-ligand 1 (PD-L1) expression appear to be suboptimal. A strong ...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-020-00723-z
更新日期:2020-06-01 00:00:00
abstract::The ubiquitin (Ub)+proteasome proteolytic pathway is responsible for the selective degradation of the majority of nuclear and cytosolic proteins. The proteasome is a high molecular weight multicatalytic protease that serves as the catalytic core of the complex Ub-dependent protein degradation pathway and is an excitin...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-010-0165-2
更新日期:2010-12-01 00:00:00
abstract::Vemurafenib, a specific inhibitor of mutated BRAF kinase, may activate wild-type BRAF and therefore induce squamous cell skin carcinomas in patients treated for melanoma. All vemurafenib clinical trials excluded patients with multiple primary malignant tumors; therefore, the action of this drug on concurrent BRAF wild...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-015-0384-7
更新日期:2016-04-01 00:00:00
abstract:BACKGROUND:In 2017, nivolumab monotherapy was shown to be effective as third- or later-line therapy in patients with advanced gastric or gastroesophageal junction cancer. OBJECTIVE:In this study, we investigated the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the outcomes of nivolumab monotherapy...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-020-00716-y
更新日期:2020-06-01 00:00:00
abstract:BACKGROUND:Hypovitaminosis D is associated with an adverse prognosis in colon cancer patients, possibly due to the effects of the vitamin on the immune system. Antibody-dependent cell-mediated cytotoxicity (ADCC) significantly contributes to the anti-tumor effects of monoclonal antibodies, including cetuximab, an epide...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-018-0586-x
更新日期:2018-10-01 00:00:00