Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Jan 2015
Multicenter StudyPhase I study of the MEK inhibitor trametinib in combination with the AKT inhibitor afuresertib in patients with solid tumors and multiple myeloma.
To identify the maximum tolerated dose (MTD) and recommended Phase II dose of MEK/AKT inhibitor combination of trametinib and afuresertib. ⋯ Continuous daily dosing of trametinib/afuresertib combination was poorly tolerated. Evaluation of intermittent dose schedule showed greater tolerability. Given the interest in combination treatment regimens of MAPK and PI3K/AKT pathway inhibitors, further study of intermittent dose schedule or combination of trametinib with more selective inhibitors may be warranted.
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Cancer Chemother. Pharmacol. · Jan 2015
Randomized Controlled Trial Multicenter Study Clinical TrialPopulation pharmacokinetic model of ibrutinib, a Bruton tyrosine kinase inhibitor, in patients with B cell malignancies.
Ibrutinib is an oral Bruton's tyrosine kinase inhibitor, recently approved for the treatment of mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) patients with at least one prior therapy. We developed a population pharmacokinetic (PK) model for ibrutinib in patients. ⋯ The proposed population PK model was able to describe the plasma concentration-time profiles of ibrutinib across various trials. The linear model indicated that the compound's PK was dose independent and time independent.