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

Chan E, Arlinghaus LR, Cardin DB, Goff L, Berlin JD, Parikh A, Abramson RG, Yankeelov TE, Hiebert S, Merchant N, Bhaskara S, Chakravarthy AB
Radiother Oncol. 2016 119 (2): 312-8

PMID: 27106554 · PMCID: PMC4961249 · DOI:10.1016/j.radonc.2016.04.013

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.

Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

MeSH Terms (12)

Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols Capecitabine Chemoradiotherapy Diffusion Magnetic Resonance Imaging Humans Male Maximum Tolerated Dose Middle Aged Pancreatic Neoplasms

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