Weekly EZN-2208 (PEGylated SN-38) in combination with bevacizumab in patients with refractory solid tumors.

ABSTRACT:

Background

Anti-angiogenic therapies such as bevacizumab upregulate hypoxia-inducible factor-1α (HIF-1α), a possible mechanism of drug resistance. Camptothecin analogues, including SN-38, have been shown to reduce the expression and transcriptional activity of HIF-1α in preclinical models. We hypothesized that co-administration of pegylated SN-38 (EZN-2208) may offset the induction of HIF-1α following bevacizumab treatment, resulting in synergistic antitumor effects.

Patients and methods

Patients with refractory solid tumors were enrolled. Objectives were to evaluate the modulation of HIF-1α protein and target genes in tumor biopsies following administration of the combination of EZN-2208 administered weekly × 3 (days 1, 8, 15) and bevacizumab administered every 2 weeks, in

SUBMITTER: Jeong W 

PROVIDER: S-EPMC7670584 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature