Open AccessWeekly EZN-2208 (PEGylated SN-38) in combination with bevacizumab in patients with refractory solid tumors
Author(s) -
Woondong Jeong,
Sook Ryun Park,
Annamaria Rapisarda,
Nicole Fer,
Robert J. Kinders,
Alice Chen,
Giovanni Melillo,
Barış Türkbey,
Seth M. Steinberg,
Peter Choyke,
James H. Doroshow,
Shivaani Kummar
Publication year - 2013
Publication title -
investigational new drugs
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 87
eISSN - 1573-0646
pISSN - 0167-6997
DOI - 10.1007/s10637-013-0048-3
Subject(s) - bevacizumab , medicine , tolerability , refractory (planetary science) , irinotecan , camptothecin , sn 38 , pharmacology , cancer research , cancer , colorectal cancer , chemotherapy , chemistry , adverse effect , physics , organic chemistry , astrobiology
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.