A phase 1 study of orally administered 5-fluoro-2’-deoxycytidine with tetrahydrouridine in patients with refractory solid tumors

We determined the RP2D for the combination of orally administered FdCyd and THU and measured prolonged stable disease and tumor suppressor gene hypomethylation in some patients, suggesting potential clinical benefit and molecular activity for this regimen in some patients. The paucity of tumor DNMT1 decreases and p16 re-expression are consistent with the lack of clinical response. However, it may also reflect the timing of on-treatment biopsies (following the 1-week break in FdCyd administration), since increases in p16-expressing CTCs were measured for the majority of CTC-assessable patients.