Induction (neoadjuvant) chemotherapy for locally advanced head and neck cancer (LAHNC) constitutes a three drug regimen consisting of a taxane, a platin, and 5-fluorouracil (TPF). TPF induction chemotherapy is effective but is associated with significant toxicity especially myelosuppression and mucositis. Overall response rates exceeding 80% and complete response (CR) rates ranging from 20 to 54% have been reported. Achieving CR correlates with good prognosis while failure to respond to induction chemotherapy predicts resistance to subsequent radiotherapy. Toward enhancing CR rates after induction therapy in LAHNC, we have initiated a trial combining the poly(ADP-ribose) polymerase inhibitor veliparib with cisplatin, 5FU and docetaxel therapy. Previously, we have shown that veliparib enhances accelerated senescence in cells and tumors treated with radiation or genotoxic therapy. Here, we intend to pursue parallel preclinical research constituting correlative studies for this trial. Thus, we intend to examine tissue culture, animal models and biopsies from treated patient tumors to understand whether accelerated senescence is a potential mediator of success in induction therapy, with or without veliparib. We also hope to identify biomarkers that indicate sensitivity to veliparib and/or induction therapy, and that indicate success of these treatments.

Public Health Relevance

Head and neck cancer remains a considerable health challenge. This study is directed at improving the initial treatment of patients to increase cures. By testing whether the PARP inhibitor veliparib can enhance chemotherapy, we hope to identify a low toxicity drug that can improve outcomes without increasing side effects.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA176843-02
Application #
8738622
Study Section
Developmental Therapeutics Study Section (DT)
Program Officer
Wolpert, Mary K
Project Start
2013-09-20
Project End
2017-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
2
Fiscal Year
2014
Total Cost
$318,014
Indirect Cost
$116,739
Name
University of Chicago
Department
Genetics
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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