Alternative scheduling of pulsatile, high dose sunitinib efficiently suppresses tumor growth.

ABSTRACT:

Background

Increased exposure to multitargeted kinase inhibitor sunitinib is associated with improved outcome, emphasizing the importance of maintaining adequate dosing and drug levels. The currently approved schedule (50 mg daily, four weeks on, two weeks off) precludes further dose-intensification. Recent data suggest that sunitinib, although initially developed as an antiangiogenic agent, has direct antitumor activity.

Methods

In this study, we tested whether a chemotherapy-like schedule of pulsatile high dose sunitinib would result in improved antitumor activity.

Results

In vitro, a single exposure to 20 μM sunitinib for 6-9 h resulted in complete inhibition of tumor cell growth and cell death conveyed through activation of caspases and autophagy upregulation. Not

SUBMITTER: Rovithi M 

PROVIDER: S-EPMC5013589 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature