A phase I pharmacokinetic (PK) study of vorinostat (V) in combination with irinotecan (I), 5-fluorouracil (5FU), and leucovorin (FOLFIRI) in advanced upper gastrointestinal cancers (AGC)

e15540 Background: Currently, advanced AGC has no clear standard regimen. The loss of transforming growth factor-β (TGFβ) response contributes to oncogenesis and has been described in gastric cancer. V, an inhibitor of histone deacetylase (HDAC) can restore TGFβ activity. We hypothesize that the addition of V to a standard chemotherapy regimen, FOLFIRI will result in improved therapeutic efficacy. Methods: AGC (esophagus, gastric, hepatocellular) patients (pts) with adequate organ function, performance status (ECOG 0–1), and 0–1 prior chemotherapy regimens are eligible for this phase 1 study to determine the MTD of V. Treatment consists of standard FOLFIRI (I 180mg/m2, leucovorin 400mg/m2, 5FU 400mg/m2 followed by 46-hr infusion 5FU 2400 mg/m2 q2w) with escalating doses of V given orally daily starting on day 2 (doses 200mg, 300mg, 400mg) in part 1 of the study. Per pre-specified design, initial intra- and inter-patient dose escalation was permitted, but then changed to a standard 3+3 design after observe...