Abstract:
Background:Biologics have gained traction for use in oncology, but have demonstrate clinical variability for efficacy and safety. Therapeutic drug monitoring (TDM) can benefit patients' outcomes from a biologic therapy when the latter has a defined therapeutic window. A clinically relevant therapeutic window may exist for biologics with established exposure-response (E-R) relationships for efficacy and/or safety and a documented maximum tolerated dose (MTD). Additionally, the inter-individual variability (IIV) on the clearance (CL) parameter could determine risks for patients falling outside the proposed therapeutic window. Materials and methods:The US Food and Drug Administration (FDA)-approved oncology biologics between 2005-2016 were reviewed via FDA "Purple Book" (FDA-repository for licensed biologics). Data were extracted from biologics' pharmacokinetic models available on the clinical pharmacology reviews published on the FDA-Approved Drug Products website. Evaluated features for biologics with established E-R relationships for efficacy and/or safety and MTD include an IIV for the CL and various other covariates including demographic factors, disease factors, blood chemistry, or immunogenicity. Results:Five therapies were identified with documented E-R relationships for both efficacy and safety including, Yervoy®(ipilimumab), Zaltrap® (ziv-aflibercept), Portrazza® (necitumumab), Adcetris® (brentuximab-vedotin), and Blincyto® (blinatumomab). The corresponding IIV on CL were: 34%, 33%, 29%, 47%, and 97%, respectively. Among the five therapies, only three had defined MTD including, brentuximab-vedotin, necitumumab, and blinatumomab. Conclusion:Of the medications examined, blinatumomab was identified as the anticancer drug with the most available information for the establishment of TDM, and hence, may benefit through the use of TDM to optimize effectiveness and minimize patients' toxicity. The approach used here may provide a generalizable framework to retrospectively identify anticancer biologics with high IIV that may benefit from TDM to improve patients' clinical outcome.
journal_name
Onco Targets Therjournal_title
OncoTargets and therapyauthors
Fleisher B,Ait-Oudhia Sdoi
10.2147/OTT.S153056subject
Has Abstractpub_date
2017-12-27 00:00:00pages
113-121issn
1178-6930pii
ott-11-113journal_volume
11pub_type
杂志文章abstract:BACKGROUND:Lapatinib is a dual epidermal growth factor receptor (EGFR) and HER2 inhibitor. Overexpression of these receptors is frequently observed in head and neck squamous cell carcinoma (HNSCC). As growing proportion of HNSCC is characterized by human papillomavirus (HPV) infection, we aimed at evaluating the effica...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S68235
更新日期:2015-02-02 00:00:00
abstract:Purpose:Anaplastic thyroid cancer (ATC) is a kind of rare thyroid cancer with very poor prognosis. Doxorubicin has been approved in ATC treatment as a single agent, but monotherapy still shows no improvement of the total survival in advanced ATC. Lenvatinib was investigated with encouraging results in treating patients...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S278349
更新日期:2020-11-02 00:00:00
abstract::Programmed cell death-1 (PD-1) immune checkpoint inhibitors have exhibited promising efficacy in various types of tumors. Here, we report an unresectable locally advanced gastric cancer (GC) with programmed cell death ligand-1 (PD-L1) positive and microsatellite instability (MSI), which exhibiting an unexpected effica...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S243298
更新日期:2020-02-26 00:00:00
abstract:Background:Bladder cancer (BC) is one of the most prevalent malignancies of the genitourinary system, yet the underlying mechanism of BC progression still remains unclear. Growth arrest and DNA damage-inducible 45 alpha (GADD45a) is a repressive gene implicated in cell cycle regulation, as well as in human cancers deve...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S222223
更新日期:2019-09-16 00:00:00
abstract:Background:Long non-coding RNAs (lncRNAs) can affect tumorigenesis. Data from The Cancer Genome Atlas (TCAG) suggest that LINC02783 is highly expressed in renal cell carcinoma (RCC) and is expected to be a potential biological target. We conducted this study to verify this. Patients and Methods:We conducted this study...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S262046
更新日期:2020-10-09 00:00:00
abstract::The fusion of echinoderm microtubule-associated protein-like 4 with anaplastic lymphoma kinase (ALK) was identified as a transforming gene for lung cancer in 2007. This genetic rearrangement accounts for 2%-5% of non-small-cell lung cancer (NSCLC) cases, occurring predominantly in younger individuals with adenocarcino...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S38868
更新日期:2014-03-05 00:00:00
abstract:INTRODUCTION:The introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has improved the outlook for patients with advanced non-small-cell lung cancer (NSCLC) with EGFR+ mutations. However, most patients develop resistance, with the result that median progression-free survival (PFS) iŝ1...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S134382
更新日期:2017-05-05 00:00:00
abstract::Purpose: NSD3 (WHSC1L1) is a protein lysine methyltransferase that is recurrently amplified (8p11.23) in several cancer types, and its upregulation is involved in tumor cell proliferation, metastasis, and epithelial-mesenchymal transition (EMT). We aimed to evaluate its potential function as an oncogenic force in colo...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S191732
更新日期:2019-05-21 00:00:00
abstract:Background and objective:RNF6, an E3 ligase, has been reported to play an important role in the tumorigenesis in several tissues, but its role in gastric cancer is still unknown. In this study, we aimed to investigate the biological function and molecular mechanisms of RNF6 in gastric cancer. Materials and methods:The...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S174846
更新日期:2018-10-05 00:00:00
abstract::Triple-negative breast cancer is associated with a poor prognosis, and effective biomarkers for targeted diagnosis and treatment are lacking. The tumorigenicity of the provirus integration site for Moloney murine leukemia virus 1 (PIM-1) gene has been studied for many years. However, its significance in breast cancer ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S212752
更新日期:2019-08-08 00:00:00
abstract:BACKGROUND:Bevacizumab plus taxane chemotherapy improves progression-free survival (PFS) versus taxane monotherapy in the first-line treatment of HER2-negative metastatic breast cancer (MBC) and appears promising in the second-line setting. This retrospective analysis evaluated the efficacy and safety of this combinati...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S70654
更新日期:2014-11-27 00:00:00
abstract:Objective:To clarify the role and mechanism of GABPB1-AS1 in renal cell carcinoma. Methods:We collected 48 pairs of tumor and adjacent normal tissues from patients with clear cell renal cell carcinoma (ccRCC). Both 786-o and caki-1 ccRCC cell lines were transfected with GA-binding protein transcription factor subunit ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S257275
更新日期:2020-07-12 00:00:00
abstract:BACKGROUND:Current cancer treatments have unexpected side effects of which the death of normal cells is one. In some cancers, iron nanoparticles (NPs) can be subjected to diagnosis and passive targeting treatment. Cold atmospheric plasma (CAP) has a proven induction of selective cell death ability. In this study, we ha...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S95644
更新日期:2016-09-28 00:00:00
abstract:OBJECTIVE:To study microRNA (miR)-20a expression in hepatocellular carcinoma (HCC) and its effects on the proliferation, migration, and invasion of HepG2. METHODS:The real-time polymerase chain reaction was used to detect the expression of miR-20a in HCC tissue and normal tissue, as well as in HCC cell lines and norma...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S96861
更新日期:2016-05-27 00:00:00
abstract::[This corrects the article DOI: 10.2147/OTT.S196910.]. ...
journal_title:OncoTargets and therapy
pub_type: 已发布勘误
doi:10.2147/OTT.S229714
更新日期:2019-09-19 00:00:00
abstract::Trastuzumab is a monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). HER2 is amplified or overexpressed in about 15% of breast cancers and is associated with aggressive disease. Clinical benefits of trastuzumab have been established in the treatment of both early and metastatic HE...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S27733
更新日期:2013-01-01 00:00:00
abstract:Objective:To compare cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and CHOP plus etoposide (CHOPE) with regard to outcomes including efficacy and safety for patients with peripheral T-cell lymphoma (PTCL). Methods:Relevant literature was searched using PubMed, Embase, Wanfang, and CNKI for eligible...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S189825
更新日期:2019-03-28 00:00:00
abstract::Mammalian nuclear receptors (NRs) are transcription factors regulating the expression of target genes that play an important role in drug metabolism, transport, and cellular signaling pathways. The orphan and structurally unique receptor small heterodimer partner 1 (syn NR0B2) is not only known for its modulation of d...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S106926
更新日期:2016-08-08 00:00:00
abstract::Recent studies have shown that microRNAs play a pivotal role in the pathogenesis of cancer. In our current study, the expression levels of microRNA-211 (miR-211) were measured in human non-small-cell lung cancer (NSCLC) tissues and cell lines. We found that miR-211 expression levels were increased in NSCLC tissues and...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S143084
更新日期:2017-11-28 00:00:00
abstract:OBJECTIVE:The objective of the present investigation was to study the clinical significances of the abnormal expressions of Piwil1 and Piwil2 protein in colonic adenoma and adenocarcinoma. METHODS:This study had applied immunohistochemical method to detect 45 cases of tissues adjacent to carcinoma (distance to cancero...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S77003
更新日期:2015-05-27 00:00:00
abstract:Purpose:Cervical squamous cell carcinoma (CSCC) seriously affects women's health worldwide, and it is of great significance to illuminate the specific role of circRNAs in CSCC. Materials and Methods:Three mRNA datasets, two miRNA datasets and one circRNA dataset of CSCC, downloaded from GEO, were utilized in this stud...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S254323
更新日期:2020-08-25 00:00:00
abstract::Circulating tumor DNA (ctDNA) can be identified in the peripheral blood of patients and harbors the genomic alterations found in tumor tissues, which provides a noninvasive approach for detection of gene mutations. We conducted this meta-analysis to investigate whether ctDNA can be used for monitoring KRAS gene mutati...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S123954
更新日期:2017-02-16 00:00:00
abstract:OBJECTIVES:PD-1/PD-L1 and CTLA-4 have been investigated and are thought to play an important role in tumor evasion. This study aimed to investigate expression patterns of immune-related molecules, and their clinical impacts in malignant salivary gland tumors. PATIENTS AND METHODS:We performed immunohistochemical stain...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S134589
更新日期:2017-06-13 00:00:00
abstract::Bladder cancer (BC) is a common urinary system tumor with high aggressiveness, and it results in relatively high mortality due to a lack of precise and suitable biomarkers. In this study, we applied the weighted gene coexpression network analysis method to miRNA expression data from BC patients, and screened for netwo...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S146479
更新日期:2017-11-22 00:00:00
abstract::Targeted therapies against EGFR, vascular endothelial growth factor, and vascular endothelial growth factor receptor have expanded treatment options for patients with metastatic colorectal cancer (mCRC). Unfortunately, biomarkers to identify patients that are most likely to derive benefit from targeted therapies in th...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S68558
更新日期:2015-12-30 00:00:00
abstract:Background:The oncogenic potential of special AT-rich binding protein 1 (SATB1) has been reported in various types of cancer, but its function in cervical cancer remains not fully investigated. This study aimed to investigate the effect of SATB1 mRNA expression on tumor progression and outcomes in the cervical cancer p...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S191414
更新日期:2019-01-30 00:00:00
abstract::MicroRNAs (miRs) have been demonstrated to play key roles in the development and progression of hepatocellular carcinoma (HCC). However, the regulatory mechanism of miR-503 in HCC has not been fully uncovered. In this study, we found that miR-503 was significantly downregulated in HCC tissues compared to nontumorous l...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S106351
更新日期:2016-06-15 00:00:00
abstract::Background: During the past decades, great efforts have been built to develop lung cancer vaccines. Whole tumor cell lysate (TCL) are ideal sources of antigens for cancer vaccine design, which however have limited efficacy due to insufficient immunogenicity. Recently, radiotherapy has been closely related to immunothe...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S197516
更新日期:2019-05-16 00:00:00
abstract::Immune checkpoint inhibitors (ICIs) have transformed the therapeutic strategy and prognosis of advanced non-small cell lung cancer (NSCLC) patients. Nowadays, ICIs as monotherapy or in combination with chemotherapy are the standard of care treatment in advanced NSCLC, and in stage III, durvalumab (a programmed death l...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S259308
更新日期:2020-07-14 00:00:00
abstract::Patients with Lynch Syndrome (LS) are at high risk of developing colorectal cancer at an early age. Germline mutations in DNA mismatch repair genes and microsatellite instability are clear signatures of this autosomal dominant disorder. Here, we report the clinical history of a 38-year-old patient with LS-related meta...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S167645
更新日期:2018-10-23 00:00:00