Tumor reoxygenation following administration of the EGFR inhibitor, gefitinib, in experimental tumors.

It is well recognized that tumor hypoxia is a critical determinant for response to therapy. The effect of an EGFR inhibitor/gefitinib (Iressa®) on tumor oxygenation was monitored daily using in vivo EPR (electron paramagnetic resonance) oximetry on TLT and FSaII tumor models. An increase in pO2 was shown at a dose of 45 mg/kg i.p. (n = 4/group/tumor model). This allowed the identification of a window of reoxygenation in both tumor models (with a maximum between 15 and 20 mmHg after 2 days of treatment). The increase in tumor oxygenation was shown to be the result of a decrease in oxygen consumption. This is the first report on the effect of gefitinib on oxygen consumption by tumor cells and subsequent increase in tumor oxygenation in vivo.