000097222 001__ 97222
000097222 005__ 20230519145343.0
000097222 0247_ $$2doi$$a10.1007/s00280-020-04153-6
000097222 0248_ $$2sideral$$a120992
000097222 037__ $$aART-2021-120992
000097222 041__ $$aeng
000097222 100__ $$aFudio, S.
000097222 245__ $$aEffect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure–response analysis
000097222 260__ $$c2021
000097222 5060_ $$aAccess copy available to the general public$$fUnrestricted
000097222 5203_ $$aPurpose: This 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. Methods: Patients with QTcF = 500 ms, QRS < 110 ms, PR < 200 ms, and normal cardiac conduction and function received lurbinectedin 3.2 mg/m2 as a 1-h intravenous infusion every 3 weeks. ECGs were collected in triplicate via 12-lead digital recorder in treatment cycle 1 and 2 and analyzed centrally. ECG collection time-matched blood samples were drawn to measure lurbinectedin plasma concentration. No effect on QTc interval was concluded if the upper bound (UB) of the least square (LS) mean two-sided 90% confidence intervals (CI) for ¿QTcF at each time point was < 20 ms. C-¿QTcF was explored using linear mixed-effects analysis. Results: A total of 1707 ECGs were collected from 39 patients (females, 22; median age, 56 years). The largest UB of the 90% CI of ¿QTcF 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 ¿QTcF at Cmax was 7.81 ms, also below the 10 ms threshold of clinical concern. Conclusions: ECG parameters and C-¿QTcF modelling in this prospective study indicate that lurbinectedin was not associated with a clinically relevant effect on cardiac repolarization.
000097222 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000097222 590__ $$a3.288$$b2021
000097222 591__ $$aPHARMACOLOGY & PHARMACY$$b160 / 279 = 0.573$$c2021$$dQ3$$eT2
000097222 591__ $$aONCOLOGY$$b168 / 245 = 0.686$$c2021$$dQ3$$eT3
000097222 594__ $$a5.9$$b2021
000097222 592__ $$a0.848$$b2021
000097222 593__ $$aCancer Research$$c2021$$dQ1
000097222 593__ $$aToxicology$$c2021$$dQ1
000097222 593__ $$aPharmacology (medical)$$c2021$$dQ1
000097222 593__ $$aOncology$$c2021$$dQ1
000097222 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000097222 700__ $$aTabernero, J.
000097222 700__ $$aSubbiah, V.
000097222 700__ $$aChawla, S.P.
000097222 700__ $$aMoreno, V.
000097222 700__ $$aLongo, F.
000097222 700__ $$aLopez, R.
000097222 700__ $$0(orcid)0000-0002-9159-4988$$aAnton, A.$$uUniversidad de Zaragoza
000097222 700__ $$aTrigo, J.M.
000097222 700__ $$aShapiro, G.
000097222 700__ $$aJeong, W.
000097222 700__ $$aVillalobos, V.M.
000097222 700__ $$aLubomirov, R.
000097222 700__ $$aFernandez-Teruel, C.
000097222 700__ $$aAlfaro, V.
000097222 700__ $$aBoni, V.
000097222 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000097222 773__ $$g87 (2021), 113–124$$pCancer chemother. pharmacol.$$tCANCER CHEMOTHERAPY AND PHARMACOLOGY$$x0344-5704
000097222 8564_ $$s660455$$uhttps://zaguan.unizar.es/record/97222/files/texto_completo.pdf$$yVersión publicada
000097222 8564_ $$s27382$$uhttps://zaguan.unizar.es/record/97222/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000097222 909CO $$ooai:zaguan.unizar.es:97222$$particulos$$pdriver
000097222 951__ $$a2023-05-18-13:17:26
000097222 980__ $$aARTICLE