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Radiother Oncol. 2016 May;119(2):312-8. doi: 10.1016/j.radonc.2016.04.013. Epub 2016 Apr 19.

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

Author information

1
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, United States.
2
Vanderbilt University Institute of Imaging Science, United States.
3
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, United States; Vanderbilt University Institute of Imaging Science, United States; Departments of Radiology and Radiological Sciences, Biomedical Engineering, Physics, and Cancer Biology, Vanderbilt University, United States.
4
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, UHealth - University of Miami Health System, United States.
5
Department of Radiation Oncology and Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, United States.
6
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, United States. Electronic address: bapsi.chak@vanderbilt.edu.

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.

KEYWORDS:

HDAC inhibitor; Magnetic resonance imaging; Neoadjuvant therapy

PMID:
27106554
PMCID:
PMC4961249
DOI:
10.1016/j.radonc.2016.04.013
[Indexed for MEDLINE]
Free PMC Article

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