Sorafenib administered using a high-dose, pulsatile regimen in patients with advanced solid malignancies: a phase I exposure escalation study.

ABSTRACT:

Background

(Pre)clinical evidence is accumulating that intermittent exposure to increased doses of protein kinase inhibitors may improve their treatment benefit. In this phase I trial, the safety of high-dose, pulsatile sorafenib was studied.

Patients and methods

High-dose sorafenib was administered once weekly in exposure escalation cohorts according to a 3 + 3 design. Drug monitoring was performed in weeks 1-3 and doses were adjusted to achieve a predefined target plasma area under the curve (AUC)(0-12 h). The effect of low gastric pH on improving sorafenib exposure was investigated by intake of the acidic beverage cola.

Results

Seventeen patients with advanced malignancies without standard treatment options were included. Once weekly, high-dose sorafenib exposure w

SUBMITTER: Mammatas LH 

PROVIDER: S-EPMC7188706 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature