Fudio, SalvadorTabernero, JosepSubbiah, VivekChawla, Sant PMoreno, VictorLongo, FedericoLopez, RafaelAnton, AntonioTrigo, Jose ManuelShapiro, GeoffreyJeong, WoondongVillalobos, Victor ManuelLubomirov, RubinFernandez-Teruel, CarlosAlfaro, VicenteBoni, Valentina2023-02-092023-02-092020-09-17Fudio S, Tabernero J, Subbiah V, Chawla SP, Moreno V, Longo F, et al. Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure-response analysis. Cancer Chemother Pharmacol. 2021 Jan;87(1):113-124http://hdl.handle.net/10668/16488This study assessed the effect of lurbinectedin, a highly selective inhibitor of oncogenic transcription, on the change from baseline in Fridericia's corrected QT interval (∆QTcF) and electrocardiography (ECG) morphological patterns, and lurbinectedin concentration-∆QTcF (C-∆QTcF) relationship, in patients with advanced solid tumors. Patients with QTcF ≤ 500 ms, QRS  A total of 1707 ECGs were collected from 39 patients (females, 22; median age, 56 years). The largest UB of the 90% CI of ΔQTcF was 9.6 ms, thus lower than the more conservative 10 ms threshold established at the ICH E14 guideline for QT studies in healthy volunteers. C-∆QTcF was better fit by an effect compartment model, and the 90% CI of predicted ΔQTcF at Cmax was 7.81 ms, also below the 10 ms threshold of clinical concern. ECG parameters and C-ΔQTcF modelling in this prospective study indicate that lurbinectedin was not associated with a clinically relevant effect on cardiac repolarization.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Cardiac repolarizationECGEffect compartmentLurbinectedinPlasma concentrationQTcFAdultAgedAntineoplastic agentsCarbolinesElectrocardiographyFemaleHeterocyclic compounds, 4 or more ringsHumansMaleMiddle agedNeoplasmsProspective studiesresearch article33108504open accessAntineoplásicosCarbolinasElectrocardiografíaNeoplasiasPersona de mediana edad10.1007/s00280-020-04153-61432-0843PMC7801313https://link.springer.com/content/pdf/10.1007/s00280-020-04153-6.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801313/pdf