Phase I and pharmacological study of pazopanib in combination with oral topotecan in patients with advanced solid tumours.

ABSTRACT:

Background

This phase I study evaluated the safety, tolerability, maximum tolerated dose (MTD) and pharmacokinetics of two dosing schedules of oral topotecan in combination with pazopanib in patients with advanced solid tumours.

Methods

Stage I of this study was to determine whether there was an impact of pazopanib on topotecan exposure. In stage II, the MTD and safety profile of oral topotecan given weekly on days 1, 8 and 15 in a 28-day cycle; or daily-times-five on days 1-5 in a 21-day cycle, both in combination with daily pazopanib, were explored.

Results

In total, 67 patients were enroled. Pazopanib co-administration caused a substantial increase in exposure to total topotecan (1.7-fold) compared with topotecan alone, which is considered clinically relevant. Topo

SUBMITTER: Kerklaan BM 

PROVIDER: S-EPMC4559826 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature