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 to characterize axitinib pharmacokinetics and safety in patients with renal impairment. PATIENTS AND METHODS:Effect of renal function (baseline creatinine clearance [CrCL]) on axitinib clearance was evaluated in a population pharmacokinetic model in 207 patients with advanced solid tumors who received a standard axitinib starting dose, and in 383 healthy volunteers. Axitinib safety according to baseline CrCL was assessed in previously treated patients with RCC (n = 350) who received axitinib in the phase 3 AXIS study. RESULTS:Median axitinib clearance was 14.0, 10.7, 12.3, 7.81, and 12.6 L/h, respectively, in individuals with normal renal function (≥90 ml/min; n = 381), mild renal impairment (60-89 ml/min; n = 139), moderate renal impairment (30-59 ml/min; n = 64), severe renal impairment (15-29 ml/min; n = 5), and end-stage renal disease (<15 ml/min; n = 1). The population pharmacokinetic model adequately predicted axitinib clearance in individuals with severe renal impairment or end-stage renal disease. Grade ≥3 adverse events (AEs) were reported in 63 % of patients with normal renal function or mild impairment, 77 % with moderate impairment, and 50 % with severe impairment; study discontinuations due to AEs were 10 %, 11 %, and 0 %, respectively. CONCLUSIONS:Axitinib pharmacokinetics and safety were similar regardless of baseline renal function; no starting-dose adjustment is needed for patients with pre-existing mild to severe renal impairment.
journal_name
Target Oncoljournal_title
Targeted oncologyauthors
Chen Y,Rini BI,Motzer RJ,Dutcher JP,Rixe O,Wilding G,Stadler WM,Tarazi J,Garrett M,Pithavala YKdoi
10.1007/s11523-015-0389-2subject
Has Abstractpub_date
2016-04-01 00:00:00pages
229-34issue
2eissn
1776-2596issn
1776-260Xpii
10.1007/s11523-015-0389-2journal_volume
11pub_type
杂志文章abstract：:With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal tox...
journal_title：Targeted oncology
pub_type： 杂志文章,评审
doi：10.1007/s11523-015-0368-7
更新日期：2015-12-01 00:00:00
abstract：BACKGROUND:The WEE1 inhibitor adavosertib (AZD1775) has been investigated in Western patients. OBJECTIVE:This open-label Phase Ib study (NCT02341456) investigated the safety, pharmacokinetics, and clinical activity of adavosertib in combination with carboplatin alone or paclitaxel plus carboplatin in Asian patients wi...
journal_title：Targeted oncology
pub_type： 杂志文章
doi：10.1007/s11523-020-00701-5
更新日期：2020-02-01 00:00:00
abstract：:Mesothelin is a tumor differentiation antigen, which is highly expressed in several solid neoplasms, including pancreatic cancer. Its selective expression on malignant cells and on only a limited number of healthy tissues has made it an interesting candidate for investigation as a diagnostic and prognostic biomarker a...
journal_title：Targeted oncology
pub_type： 杂志文章,评审
doi：10.1007/s11523-018-0567-0
更新日期：2018-06-01 00:00:00
abstract：:In anticancer drug development, there has been increasing consideration for the potential of a compound to cause adverse electrocardiographic changes, especially QT interval prolongation, which can be associated with risk of torsades de pointes and sudden death. Irrespective of overt clinical toxicities, QTc assessmen...
journal_title：Targeted oncology
pub_type： 杂志文章,评审
doi：10.1007/s11523-014-0325-x
更新日期：2015-03-01 00:00:00
abstract：:Several angiogenesis inhibitors have been approved for commercial use and many additional agents are under development for the treatment of various malignancies. Cardiovascular toxicities have been increasingly recognized as effects of this entire class of new anticancer therapeutics. There is a limited but growing un...
journal_title：Targeted oncology
pub_type： 杂志文章,评审
doi：10.1007/s11523-009-0106-0
更新日期：2009-04-01 00:00:00
abstract：BACKGROUND:Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations. OBJECTIVE:The purpose of this study was to assess...
journal_title：Targeted oncology
pub_type： 杂志文章
doi：10.1007/s11523-017-0497-2
更新日期：2017-08-01 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：:Personalized medicine is defined by the National Cancer Institute as "a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, and treat disease." In oncology, the term "personalized medicine" arose with the emergence of molecularly targeted agents. The prescript...
journal_title：Targeted oncology
pub_type： 杂志文章,评审
doi：10.1007/s11523-012-0237-6
更新日期：2012-12-01 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：:Basal transcription regulation of the epidermal growth factor receptor is dependent upon a CA simple sequence repeat polymorphism in the intron-1 (CA-SSR-1). Here, we evaluate the role of CA-SSR-1 in complete resected esophageal cancer (EC) patients without neoadjuvant or adjuvant treatment. Genomic DNA was extracted ...
journal_title：Targeted oncology
pub_type： 杂志文章
doi：10.1007/s11523-013-0260-2
更新日期：2014-03-01 00:00:00
abstract：:Data regarding the expression of epidermal growth factor receptor (EGFR) in melanoma and its role in the tumor biology are conflicting. In BRAF V600-mutant melanomas, the expression of EGFR has been associated with acquired resistance to BRAF inhibitors. In this study, we assessed EGFR expression and downstream signal...
journal_title：Targeted oncology
pub_type： 杂志文章
doi：10.1007/s11523-014-0318-9
更新日期：2015-03-01 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：: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：: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：:The poly(ADP-ribose) polymerase inhibitor rucaparib is approved as monotherapy in the treatment and maintenance settings for women with relapsed ovarian cancer in the European Union and the United States. We review the safety profile of rucaparib in both settings and provide recommendations for the clinical management...
journal_title：Targeted oncology
pub_type： 杂志文章
doi：10.1007/s11523-020-00715-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：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
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:The identification of prognostic and/or predictive biomarkers for response to immune checkpoint inhibitors (ICI) could help guide treatment decisions. OBJECTIVE:We assessed changes in programmed cell death-1 (PD1)/PD1 ligand (PDL1) expression in key immunomodulatory cell subsets (myeloid-derived suppressor ...
journal_title：Targeted oncology
pub_type： 杂志文章
doi：10.1007/s11523-018-0595-9
更新日期：2018-10-01 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：: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：:The discovery of chemoresistant cancer stem cells (CSCs) in carcinomas has created the need for therapies that specifically target these subpopulations of cells. Here, we characterized a bispecific targeted toxin that is composed of two antibody fragments and a catalytic protein toxin allowing it to bind two CSC marke...
journal_title：Targeted oncology
pub_type： 杂志文章
doi：10.1007/s11523-013-0290-9
更新日期：2014-09-01 00:00:00
abstract：:Among neuroendocrine carcinomas of the gut, well-differentiated tumors are highly vascularized, featuring specific characteristics on contrast-enhanced imaging. Well-differentiated neuroendocrine tumors spontaneously harbor hypervascular enhancement, coexisting with areas of necrosis mainly located at the center of tu...
journal_title：Targeted oncology
pub_type： 杂志文章
doi：10.1007/s11523-012-0216-y
更新日期：2012-06-01 00:00:00
abstract：BACKGROUND:Immunotherapy based on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has revolutionized the treatment of non-small cell lung cancer (NSCLC). Patients with high PD-L1 expression or DNA mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) cancer are re...
journal_title：Targeted oncology
pub_type： 杂志文章
doi：10.1007/s11523-020-00703-3
更新日期：2020-02-01 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：BACKGROUND:The variability in progression-free survival (PFS) and overall survival (OS) among patients with epithelial ovarian cancer (EOC) makes it difficult to reliably predict outcomes. A predictive biomarker of bevacizumab efficacy as first-line therapy in EOC is still lacking. OBJECTIVE:The MITO group conducted a...
journal_title：Targeted oncology
pub_type： 杂志文章,多中心研究
doi：10.1007/s11523-018-0574-1
更新日期：2018-08-01 00:00:00
abstract：:The currently prevalent somatic mutation theory of carcinogenesis and metastases explicitly assumes that cancer is a cellular disease, i.e. a disease of the control of cell proliferation and/or cell differentiation. Accordingly, explanations should always be sought for at a gene and/or gene product level, regardless o...
journal_title：Targeted oncology
pub_type： 杂志文章,评审
doi：10.1007/s11523-013-0277-6
更新日期：2013-06-01 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：: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
