Phase I trial of chemoradiation with capecitabine and vorinostat in pancreatic cancer.

225 Background: Histone deacetylase inhibitors (HDACi) and fluoropyrimidines are synergistic and are radiation (R) sensitizers. The combination of the fluoropyrimidine capecitabine ( C) and the HDACi vorinostat (V) with R was evaluated in the treatment (tx) of non-metastatic pancreatic cancer (NMPC). Methods: Patients (Pts) with NMPC were treated with C + V + R. C dose was 1000 mg q12 Monday (M) - Friday (F) on the days of R. R was given via 3D conformal therapy to a total dose of 3000 cGy in 10 fractions over 2 weeks (wk). V dose was given daily M-F x 4 wk. V doses evaluated were: 100, 200, 300, and 400 mg. Resectability assessment occurred within 6 wk after completion of tx. Diffusion weighted- MRIs (DW-MRIs) were obtained pre tx and one wk after tx initiation to assess tumor cellularity. Peripheral blood mononuclear cells (PBMCs) were collected pre tx, during tx, and after completion to assess whole cell HDAC activity. Unresectable pts could opt for continuation of C and V (CCV) at systemic doses (C 10...