Abstract:
BACKGROUND:Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are rapidly being developed for treatment of non-small-cell lung cancer (NSCLC) in patients harboring EGFR T790M mutations. This first-in-human phase 1 study evaluated the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, tolerability, and pharmacokinetics (PK), and preliminarily determined the antitumor activity of ES-072 in NSCLC patients with EGFR T790M mutations. PATIENTS AND METHODS:Dose escalation and expansion studies were performed using an accelerated titration method. Oral ES-072 doses (25-450 mg) were administrated once daily for single- and multiple-dose escalation trials. Characteristic PK parameters were assessed in the single-dose escalation phase and in the first cycle of the multiple-dose escalation phase. Tumor responses were assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 to evaluate ES-072 antitumor activity. RESULTS:Nineteen patients were enrolled onto this study, 16 to the dose-escalation phase and 3 to the dose-expansion phase. The most common adverse events were QT interval prolongation (11/19, 57.9%), anemia (5/19, 26.3%), mouth ulceration (4/19, 21.1%), keratosis (4/19, 21.1%), and cough (4/19, 21.1%). Safety and tolerability evaluation of ES-072 showed an maximum tolerated dose of 300 mg, and the RP2D dose was therefore 300 mg once daily. PK analysis showed an ES-072 half-life of 24.5 hours and a Tmax of approximately 4 hours. The total objective response rate and disease control rate were 46.2% and 76.9%, respectively. CONCLUSION:ES-072 was safe and well tolerated in NSCLC patients harboring EGFR T790M mutations, and adverse events were controllable and reversible. A RP2D of 300 mg once daily was determined, and preliminary investigations showed promising antitumor activity.
journal_name
Clin Lung Cancerjournal_title
Clinical lung cancerauthors
Zheng J,Shen L,Jiang N,Zhu Y,Wu L,Cao H,Sun W,Zhou J,Zhou Jdoi
10.1016/j.cllc.2020.07.001subject
Has Abstractpub_date
2020-11-01 00:00:00pages
509-519.e1issue
6eissn
1525-7304issn
1938-0690pii
S1525-7304(20)30223-0journal_volume
21pub_type
杂志文章abstract::Lung cancer continues to be the leading cause of cancer-related death in the United States. Small-cell lung cancer constitutes 15%-20% of all cases of lung cancer. It is a chemosensitive disease with an overall response rate of 70%-90% in first-line treatment. However, the majority of patients relapse, and further tre...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/clc.2001.n.010
更新日期:2001-05-01 00:00:00
abstract::Metastatic non-small-cell lung cancer is generally not considered to be curable, and the overall 5-year survival rate is less than 1%. Despite this poor prognosis, palliative chemotherapy can increase time and quality of life in the advanced-disease setting. New chemotherapy treatments and targeted therapies are avail...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2011.06.007
更新日期:2011-11-01 00:00:00
abstract::The absolute number of patients with lung cancer is rising as a result of our aging population. Until recently, clinicians have been reluctant to aggressively treat elderly patients with non-small-cell lung cancer (NSCLC) because of a lack of supportive data and concern for potential toxicity. Recently, evidence has e...
journal_title:Clinical lung cancer
pub_type: 杂志文章,评审
doi:10.3816/CLC.2005.n.031
更新日期:2005-11-01 00:00:00
abstract:INTRODUCTION:The lung is a heterogeneous organ with relative overperfusion of the lung bases. We determined whether a lower lobe primary tumor location was associated with poor outcomes in the setting of stage I non-small-cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). PATIENTS AND ME...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2016.09.001
更新日期:2017-03-01 00:00:00
abstract::This article describes the treatment rationale and study-related procedures for the A Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-Small-Cell Lung Cancer Following Disease Progression after One Prior Platinum-Based Therapy (REVEL) st...
journal_title:Clinical lung cancer
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.cllc.2012.06.007
更新日期:2012-11-01 00:00:00
abstract:PURPOSE:We conducted a phase I trial of the topoisomerase I inhibitor topotecan for the purpose of determining the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of topotecan when administered weekly to patients with advanced non-small-cell lung cancer. PATIENTS AND METHODS:Twelve patients with s...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/CLC.2010.n.035
更新日期:2010-07-01 00:00:00
abstract:INTRODUCTION:Pneumonitis is one of the immune-related adverse events of programmed death 1 (PD-1) inhibitors that sometimes cause lethal outcomes. Although some recent reports have described PD-1 inhibitors as more effective in non-small-cell lung cancer (NSCLC) patients with immune-related adverse events than in those...
journal_title:Clinical lung cancer
pub_type: 杂志文章,多中心研究
doi:10.1016/j.cllc.2019.07.006
更新日期:2019-11-01 00:00:00
abstract::Both gemcitabine and carboplatin have demonstrated activity in advanced non small-cell lung cancer. The combination of gemcitabine and cisplatin has demonstrated equivalent or superior efficacy to other commonly used agents and two-drug combinations, and a recent Eastern Cooperative Oncology Group trial suggested that...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/clc.2000.s.008
更新日期:2000-12-01 00:00:00
abstract::After decades of platinum-based chemotherapy for advanced small-cell lung cancer, there has finally been a therapeutic advance. The combination of a platinum chemotherapy, etoposide, and an immune checkpoint inhibitor has yielded overall survival benefits in two successive phase 3 trials. Unfortunately, these trials o...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2020.04.006
更新日期:2020-11-01 00:00:00
abstract::This study was designed as a multicenter, randomized, double-blind, placebo-controlled trial. Patients were randomized by center to placebo (16 patients, 31%), oral bexarotene 300 mg/m2/day (21 patients, 40%), or oral bexarotene 600 mg/m2/day (15 patients, 29%) following demonstration of stable or responsive disease a...
journal_title:Clinical lung cancer
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.3816/clc.2001.n.005
更新日期:2001-02-01 00:00:00
abstract:BACKGROUND:The benefits of immune checkpoint inhibitors for first-line treatment in patients with lung adenocarcinoma harboring EGFR mutations are unclear. The effects of ICIs depend on the tumor microenvironment (TME). Differences in TME properties between mutant and wild-type EGFR have not been fully characterized. ...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2018.03.011
更新日期:2018-09-01 00:00:00
abstract::Current treatments of non-small-cell lung cancer (NSCLC) are inadequate and new therapies are being developed that target specific cellular signaling proteins associated with tumor growth. One potential target is protein kinase C (PKC)-alpha, a signaling molecule with an important role in cell regulation and prolifera...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/clc.2004.n.032
更新日期:2004-11-01 00:00:00
abstract:INTRODUCTION:A recent review of phase I trials suggests that participation in these trials can be associated with clinical benefit and the rate of drug-related deaths is low. We conducted an analysis of the Cancer Therapy Evaluation Program (CTEP)-sponsored phase I trials to assess the outcomes of lung cancer patients ...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2011.03.022
更新日期:2011-07-01 00:00:00
abstract:BACKGROUND:It is unclear what proportion of VTE events in lung cancer patients are incidentally discovered and whether incidental events affect mortality. PATIENTS AND METHODS:We conducted a retrospective cohort study of lung cancer patients seen at the University of Rochester between January 1, 2006 and December 31, ...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2013.06.003
更新日期:2013-11-01 00:00:00
abstract:BACKGROUND:Hormesis is a favorable biological response to low toxin exposure. In the case of radiation, large doses are carcinogenic, but low doses might be protective. In the current study, we analyzed lung cancer incidence in high-impact radiation states where nuclear testing occurred and compared it with lung cancer...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2014.09.010
更新日期:2015-03-01 00:00:00
abstract:BACKGROUND:Patients with advanced non-small-cell lung cancer (NSCLC) and poor performance status (PS) are often excluded from trials. Gefitinib is a safe oral agent that may benefit these patients. PATIENTS AND METHODS:Seventy-two patients with poor PS and advanced NSCLC were enrolled onto this study of gefitinib 250 ...
journal_title:Clinical lung cancer
pub_type: 杂志文章,多中心研究
doi:10.3816/CLC.2005.n.028
更新日期:2005-09-01 00:00:00
abstract:BACKGROUND:Evidence favoring a multidisciplinary team (MDT) approach in the treatment of lung cancer is scarce, especially in the United States. The purpose of the present investigation was to evaluate survival outcomes of lung cancer patients treated with an MDT compared with a traditional care model. PATIENTS AND ME...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2018.01.006
更新日期:2018-07-01 00:00:00
abstract::An early phase II study of topotecan produced favorable results in a small number of untreated and previously treated patients with small-cell lung cancer (SCLC). This multicenter study was conducted in patients with relapsed SCLC at 19 medical institutions in Japan. Topotecan 1.0 mg/m2/day was administered for 5 cons...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/clc.2003.n.002
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:A few reports have evaluated the outcomes of concurrent chemoradiotherapy (CRT) for patients with postoperative recurrence of non-small cell lung cancer (NSCLC). PATIENTS AND METHODS:From 2000 through 2011, 1237 consecutive patients with NSCLC underwent pulmonary resection at our institution. Of those, 280 ...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2014.06.001
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:ROS1 gene fusions cause several cancers by constitutively activating the ROS1 tyrosine kinase receptor. ROS1-targeted inhibitor therapy improves survival in the approximately 1% to 2% of patients with lung adenocarcinoma with ROS1 gene fusions. Although fluorescence in situ hybridization (FISH) is the standa...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2014.10.003
更新日期:2015-03-01 00:00:00
abstract:BACKGROUND:Little is known about the difference between black and non-black patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), particularly regarding survival. We thus characterized the EGFR expression profile, clinical characteristics, and survival outcome in these patien...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2019.07.003
更新日期:2020-03-01 00:00:00
abstract:OBJECTIVE:The objective of this study is to externally validate the 8th Edition of the Tumor, Node, and Metastasis staging system and its updated T descriptors in patients with non-small cell lung cancer with N3 disease. METHODS:Data were extracted from the Surveillance, Epidemiology, and End Results database. Chi-squ...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2017.05.009
更新日期:2017-11-01 00:00:00
abstract:INTRODUCTION:Small-cell lung cancer is an aggressive disease for which the mainstay of treatment is chemotherapy. Despite good initial responses most patients will relapse. Some will receive second-line therapy with clinical benefit, but for third-line chemotherapy there is little evidence to guide treatment decisions ...
journal_title:Clinical lung cancer
pub_type: 杂志文章,多中心研究
doi:10.1016/j.cllc.2013.11.003
更新日期:2014-03-01 00:00:00
abstract::Two cases of complications secondary to the use of microwave ablation (MWA) in non-small-cell lung cancer (NSCLC) are discussed herein. The first case involves a 62-year-old man with stage IB NSCLC who declined surgery and pursued MWA. Within 7 months, he had residual disease at the MWA treatment site, and surgery was...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/CLC.2008.n.019
更新日期:2008-03-01 00:00:00
abstract:BACKGROUND:Afatinib is approved in the US, Europe, and several other regions for first-line treatment for epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS:Treatment-naive patients with advanced EGFRm+ NSCLC were randomized to afatinib (40 mg/d) versus...
journal_title:Clinical lung cancer
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.cllc.2018.03.009
更新日期:2018-07-01 00:00:00
abstract::The insulin-receptor substrate family plays important roles in cellular growth, signaling, and survival. Two new members of this family have recently been isolated: IRS5/Dok4 and IRS6/Dok5. This study examines the expression of IRS5/DOK4 in a panel of lung cancer cell lines and tumor specimens. The results demonstrate...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/CLC.2008.n.053
更新日期:2008-11-01 00:00:00
abstract:INTRODUCTION:The objective of this study was to present the outcomes of moderately hypofractionated helical intensity-modulated radiation therapy (HT) with/without simultaneous integrated boost (SIB) on fluorodeoxyglucose-positron emission tomography (FDG-PET) positive areas (gross tumor volume [GTV]-PET) for patients ...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2018.08.019
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Malignant pleural effusion (MPE) has a profound impact on quality of life and survival in patients with lung cancer. Identification of the factors within the tumor and its environment that mediate MPE is still lacking. PATIENTS AND METHODS:Intratumoral microvessel density (MVD), endothelial cell and pericyt...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2013.06.007
更新日期:2013-11-01 00:00:00
abstract:INTRODUCTION:Non-small-cell lung cancer (NSCLC) patients harboring ALK or ROS1 rearrangements invariably acquire resistance to the first- and second-generation tyrosine kinase inhibitors (TKIs), most notably ALK G1202R and ROS1 G2032R. Lorlatinib, a novel third-generation TKI, produced remarkable results from the first...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2018.12.020
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Y-box binding protein 1 (YB-1) is an oncogenic transcription factor that is activated in response to various genotoxic stresses. The purpose of this study was to elucidate whether YB-1 correlates with the expression of lung resistance-related protein (LRP) and epidermal growth factor receptor (EGFR) in prima...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2011.11.006
更新日期:2012-09-01 00:00:00