Cancer chemotherapy and pharmacology
-
Cancer Chemother. Pharmacol. · Sep 2016
Multicenter StudyPhase 1 study to evaluate the effect of the MEK inhibitor trametinib on cardiac repolarization in patients with solid tumours.
Trametinib is a reversible, selective inhibitor of the mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and 2 (MEK2). Cardiotoxicity (congestive heart failure, decreased heart rate, left ventricular dysfunction, and hypertension) related to trametinib is an infrequent, but serious, adverse event (AE). Prolongation of the QT interval increases the risk of life-threatening cardiac arrhythmia. Thus, the risk of trametinib inducing QT prolongation at putative supratherapeutic exposure was evaluated. ⋯ The results of this study suggest trametinib has no significant effect on QT prolongation at supratherapeutic exposure.
-
Cancer Chemother. Pharmacol. · Sep 2016
Ethnic sensitivity assessment of the antibody-drug conjugate trastuzumab emtansine (T-DM1) in patients with HER2-positive locally advanced or metastatic breast cancer.
Trastuzumab emtansine (T-DM1) is indicated for previously treated HER2-positive metastatic breast cancer. Ethnic sensitivity assessment of T-DM1 was conducted using data from eight clinical studies to ensure that the clinically recommended dose is appropriate across ethnicities. ⋯ These results suggest that T-DM1 pharmacokinetics are comparable across ethnic groups and that use of the current dosing regimen is appropriate across ethnicities.