Phase II Study of Dasatinib in Patients With Advanced Non–Small-Cell Lung Cancer

Johnson, Faye M.; Bekele, B. Nebiyou; Feng, Lei; Wistuba, Ignacio I.; Tang, Xi; Tran, Hai T.; Erasmus, Jeremy J.; Hwang, L.; Takebe, Naoko; Blumenschein, George R.; Lippman, Scott M.; Stewart, David J.

doi:10.1200/jco.2010.30.5474

Cited by 147 publications

(109 citation statements)

References 37 publications

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“…Concordant with these observations, a later study conducted by Li et al reported that EphA2, EphB2 and EphB4 were identified as targets of dasatinib in lung cancer, using quantitative phosphoproteomics [41]. Although a phase II study of dasatinib in molecular unselected patients with advanced NSCLC unfortunately showed disappointing activity, this inhibitor might be administrated on a potential subpopulation of patients with dasatinib-sensitive NSCLC, or be applied in combination therapy for NSCLC, which needs identification by further studies [42]. Other than multi-target RTK inhibitor, Noberini et al in Pasquale EB's lab identified two isomeric 2, 5-dimethylpyrrolyl benzoic acid derivatives able to selectively inhibit ephrin binding to EphA4 and EphA2 as well as the function of these receptors in live cells [43].…”

Section: Potential Therapeutic Reagents Targeting Ephs/ Ephrins In Lumentioning

confidence: 72%

The roles and therapeutic potentials of Ephs and ephrins in lung cancer

Xie

2013

Experimental Cell Research

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Section: Potential Therapeutic Reagents Targeting Ephs/ Ephrins In Lumentioning

confidence: 72%

The roles and therapeutic potentials of Ephs and ephrins in lung cancer

Xie

2013

Experimental Cell Research

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“…QTc prolongation was frequent (>5% of patients experiencing CTCAE scale grade I QTc prolongation) in patients treated with dasatinib, vandetanib, sorafenib, or sunitinib. Dasatinib is used to treat hematological malignancies and has been associated with QTc prolongation in 8% of treated patients (range, 1%–70%), but QTc >500 ms was seen only in <1% 13, 18, 20, 21, 22, 25, 32, 40, 42, 75…”

Section: Resultsmentioning

confidence: 99%

Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review

Porta‐Sánchez

Gilbert

Spears

et al. 2017

JAHA

159

142

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BackgroundThe cardiovascular complications of cancer therapeutics are the focus of the burgeoning field of cardio‐oncology. A common challenge in this field is the impact of cancer drugs on cardiac repolarization (ie, QT prolongation) and the potential risk for the life‐threatening arrhythmia torsades de pointes. Although QT prolongation is not a perfect marker of arrhythmia risk, this has become a primary safety metric among oncologists. Cardiologists caring for patients receiving cancer treatment should become familiar with the drugs associated with QT prolongation, its incidence, and appropriate management strategies to provide meaningful consultation in this complex clinical scenario.Methods and ResultsIn this article, we performed a systematic review (using Preferred Reporting Items of Systematic Reviews and Meta‐Analyses (PRISMA) guidelines) of commonly used cancer drugs to determine the incidence of QT prolongation and clinically relevant arrhythmias. We calculated summary estimates of the incidence of all and clinically relevant QT prolongation as well as arrhythmias and sudden cardiac death. We then describe strategies to prevent, identify, and manage QT prolongation in patients receiving cancer therapy. We identified a total of 173 relevant publications. The weighted incidence of any corrected QT (QTc) prolongation in our systematic review in patients treated with conventional therapies (eg, anthracyclines) ranged from 0% to 22%, although QTc >500 ms, arrhythmias, or sudden cardiac death was extremely rare. The risk of QTc prolongation with targeted therapies (eg, small molecular tyrosine kinase inhibitors) ranged between 0% and 22.7% with severe prolongation (QTc >500 ms) reported in 0% to 5.2% of the patients. Arrhythmias and sudden cardiac death were rare.ConclusionsOur systematic review demonstrates that there is variability in the incidence of QTc prolongation of various cancer drugs; however, the clinical consequence, as defined by arrhythmias or sudden cardiac death, remains rare.

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“…The efficacy results and favorable toxicity profile (in particular regarding the hematotoxicity) prompted us to launch a phase II study exploring the efficacy and toxicity of bortezomib single agent in untreated stage IV NSCLC. Such an approach had previously being reported by our group as well as others with innovative compounds [14,15].…”

Section: Introductionmentioning

confidence: 82%