Phase I trial of vorinostat added to chemoradiation with capecitabine in pancreatic cancer.
This single institution phase I trial determined the maximum tolerated dose (MTD) of concurrent vorinostat and capecitabine with radiation in non-metastatic pancreatic cancer.



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.



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).



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.
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, United States.
Emily
E
Chan
Vanderbilt University Institute of Imaging Science, United States.
Lori R
LR
Arlinghaus
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, United States.
Dana B
DB
Cardin
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, United States.
Laura
L
Goff
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, United States.
Jordan D
JD
Berlin
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, United States.
Alexander
A
Parikh
Vanderbilt University Institute of Imaging Science, United States.
Richard G
RG
Abramson
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.
Thomas E
TE
Yankeelov
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, United States.
Scott
S
Hiebert
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, UHealth - University of Miami Health System, United States.
Nipun
N
Merchant
Department of Radiation Oncology and Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, United States.
Srividya
S
Bhaskara
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, United States. Electronic address: bapsi.chak@vanderbilt.edu.
Anuradha Bapsi
AB
Chakravarthy
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage*; D059248:Chemoradiotherapy; D038524:Diffusion Magnetic Resonance Imaging; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*
D000069287:Capecitabine
HDAC inhibitor; Magnetic resonance imaging; Neoadjuvant therapy