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The Hiebert Laboratory

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

AUTHORS

Chan EEmily , Arlinghaus LRLori R , Cardin DBDana B , Goff LLaura , Berlin JDJordan D , Parikh AAlexander , Abramson RGRichard G , Yankeelov TEThomas E , Hiebert SScott , Merchant NNipun , Bhaskara SSrividya , Chakravarthy ABAnuradha Bapsi . Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2016 04 19; 119(2). 312-8

ABSTRACT

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 (100-400mg daily) during radiation. Capecitabine was given 1000mg q12 on the days of radiation. Radiation consisted of 30Gy in 10 fractions. Vorinostat dose escalation followed the standard 3+3 design. No dose escalation beyond 400mg 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 400mg. Dose limiting toxicities occurred in one patient each at dose levels 100mg, 300mg, and 400mg: 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 1.1years (95% confidence interval 0.78-1.35).

CONCLUSIONS: The combination of vorinostat 400mg daily M-F and capecitabine 1000mg q12 M-F with radiation (30Gy in 10 fractions) was well tolerated with encouraging median overall survival.