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

Background and purpose: This single institution phase I trial determined the maximum tolerated dose (MTD) of concurrent vorinostat and capecitabine with radiation in non-metastatic pancreatic cancer. Material and methods: Twenty-one patients received escalating doses of vorinostat (100-400 mg daily) during radiation. Capecitabine was given 1000 mg q12 on the days of radiation. Radiation consisted of 30 Gy in 10 fractions. Vorinostat dose escalation followed the standard 3 + 3 design. No dose escalation beyond 400 mg vorinostat was planned. Diffusion-weighted (DW)-MRI pre- and post-treatment was used to evaluate in vivo tumor cellularity. Results: The MTD of vorinostat was 400 mg. Dose limiting toxicities occurred in one patient each at dose levels 100 mg, 300 mg, and 400 mg: 2 gastrointestinal toxicities and one thrombocytopenia. The most common adverse events were lymphopenia (76%) and nausea (14%). The apparent diffusion coefficient (ADC) increased in most tumors. Nineteen (90%) patients had stable disease, and two (10%) had progressive disease at time of surgery. Eleven patients underwent surgical exploration with four R0 resections and one R1 resection. Median overall survival was 1.1 years (95% confidence interval 0.78-1.35). Conclusions: The combination of vorinostat 400 mg daily M-F and capecitabine 1000 mg q12 M-F with radiation (30 Gy in 10 fractions) was well tolerated with encouraging median overall survival. (C) 2016 Elsevier Ireland Ltd. All rights reserved.