Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure–response analysis

Cardiac repolarization; Lurbinectedin; Plasma concentration

Detalhes bibliográficos
Autores: Fudio, Salvador, Tabernero Caturla, Josep, Chawla, Sant P., Longo-Muñoz, Federico, Subbiah, Vivek, Moreno, Victor
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:11351/7752
Acesso em linha:https://hdl.handle.net/11351/7752
Access Level:acceso abierto
Palavra-chave:Càncer - Tractament
Medicaments antineoplàstics
Medicaments - Efectes fisiològics
DISEASES::Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Other subheadings::Other subheadings::Other subheadings::/administration & dosage
ENFERMEDADES::neoplasias
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
Otros calificadores::Otros calificadores::Otros calificadores::/administración & dosificación
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oai_identifier_str oai:recercat.cat:11351/7752
network_acronym_str ES
network_name_str España
repository_id_str
spelling Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure–response analysisFudio, SalvadorTabernero Caturla, JosepChawla, Sant P.Longo-Muñoz, FedericoSubbiah, VivekMoreno, VictorCàncer - TractamentMedicaments antineoplàsticsMedicaments - Efectes fisiològicsDISEASES::NeoplasmsOther subheadings::Other subheadings::Other subheadings::/drug therapyCHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic AgentsOther subheadings::Other subheadings::Other subheadings::/administration & dosageENFERMEDADES::neoplasiasOtros calificadores::Otros calificadores::Otros calificadores::/farmacoterapiaCOMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicosOtros calificadores::Otros calificadores::Otros calificadores::/administración & dosificaciónCardiac repolarization; Lurbinectedin; Plasma concentrationRepolarización cardíaca; Lurbinectedina; Concentración plasmáticaRepolarització cardíaca; Lurbinectedina; Concentració plasmàticaPurpose 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 ΔQTcF 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 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. Conclusions ECG parameters and C-ΔQTcF modelling in this prospective study indicate that lurbinectedin was not associated with a clinically relevant effect on cardiac repolarization.This study was funded by Pharma Mar S.A. and partially funded by the Industrial and Technological Development Center–CDTI (IDI-20150006).SpringerInstitut Català de la Salut[Fudio S] PharmaMar, 28770 Madrid, Spain. [Tabernero J] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Subbiah V] The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [Chawla SP] Sarcoma Oncology Center, Santa Monica, CA 90403, USA. [Moreno V] Fundación Jiménez Díaz, 28040 Madrid, Spain. [Longo F] Hospital Ramon y Cajal, 28034 Madrid, SpainVall d'Hebron Barcelona Hospital Campus2022202220202021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/7752Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésCancer Chemotherapy and Pharmacology;87https://doi.org/10.1007/s00280-020-04153-6Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/77522026-05-29T05:05:01Z
dc.title.none.fl_str_mv Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure–response analysis
title Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure–response analysis
spellingShingle Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure–response analysis
Fudio, Salvador
Càncer - Tractament
Medicaments antineoplàstics
Medicaments - Efectes fisiològics
DISEASES::Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Other subheadings::Other subheadings::Other subheadings::/administration & dosage
ENFERMEDADES::neoplasias
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
Otros calificadores::Otros calificadores::Otros calificadores::/administración & dosificación
title_short Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure–response analysis
title_full Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure–response analysis
title_fullStr Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure–response analysis
title_full_unstemmed Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure–response analysis
title_sort Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure–response analysis
dc.creator.none.fl_str_mv Fudio, Salvador
Tabernero Caturla, Josep
Chawla, Sant P.
Longo-Muñoz, Federico
Subbiah, Vivek
Moreno, Victor
author Fudio, Salvador
author_facet Fudio, Salvador
Tabernero Caturla, Josep
Chawla, Sant P.
Longo-Muñoz, Federico
Subbiah, Vivek
Moreno, Victor
author_role author
author2 Tabernero Caturla, Josep
Chawla, Sant P.
Longo-Muñoz, Federico
Subbiah, Vivek
Moreno, Victor
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Fudio S] PharmaMar, 28770 Madrid, Spain. [Tabernero J] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Subbiah V] The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [Chawla SP] Sarcoma Oncology Center, Santa Monica, CA 90403, USA. [Moreno V] Fundación Jiménez Díaz, 28040 Madrid, Spain. [Longo F] Hospital Ramon y Cajal, 28034 Madrid, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Càncer - Tractament
Medicaments antineoplàstics
Medicaments - Efectes fisiològics
DISEASES::Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Other subheadings::Other subheadings::Other subheadings::/administration & dosage
ENFERMEDADES::neoplasias
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
Otros calificadores::Otros calificadores::Otros calificadores::/administración & dosificación
topic Càncer - Tractament
Medicaments antineoplàstics
Medicaments - Efectes fisiològics
DISEASES::Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Other subheadings::Other subheadings::Other subheadings::/administration & dosage
ENFERMEDADES::neoplasias
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
Otros calificadores::Otros calificadores::Otros calificadores::/administración & dosificación
description Cardiac repolarization; Lurbinectedin; Plasma concentration
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/7752
url https://hdl.handle.net/11351/7752
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cancer Chemotherapy and Pharmacology;87
https://doi.org/10.1007/s00280-020-04153-6
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv Scientia
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869418725928599552
score 15,81155

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