Intratumoral delivery of docetaxel enhances antitumor activity of Ad-p53 in murine head and neck cancer xenograft model☆
Received 18 May 2008 published online 27 March 2009.
Abstract
Purpose
The aim of this study is to determine the ability of intratumorally delivered docetaxel to enhance the antitumor activity of adenovirus-mediated delivery of p53 (Ad-p53) in murine head and neck cancer xenograft model.
Materials and methods
A xenograft head and neck squamous cell carcinoma mouse model was used. Mice were randomized into 4 groups of 6 mice receiving 6 weeks of biweekly intratumoral injection of (a) diluent, (b) Ad-p53 (1 × 1010 viral particles per injection), (c) docetaxel (1 mg/kg per injection), and (d) combination of Ad-p53 (1 × 1010 viral particles per injection) and docetaxel (1 mg/kg per injection). Tumor size, weight, toxicity, and overall and disease-free survival rates were determined.
Results
Intratumoral treatments with either docetaxel alone or Ad-p53 alone resulted in statistically significant antitumor activity and improved survival compared with control group. Furthermore, combined delivery of Ad-p53 and docetaxel resulted in a statistically significant reduction in tumor weight when compared to treatment with either Ad-p53 or docetaxel alone.
Conclusion
Intratumoral delivery of docetaxel enhanced the antitumor effect of Ad-p53 in murine head and neck cancer xenograft model. The result of this preclinical in vivo study is promising and supports further clinical testing to evaluate efficacy of combined intratumoral docetaxel and Ad-p53 in treatment of head and neck cancer.
aDepartment of Otolaryngology-Head and Neck Surgery, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA
bDepartment of Surgery, John D. Dingell VA Medical Center, Detroit, MI, USA
cDepartment of Pathology, Wayne State University and Karmanos Cancer Institute, Detroit, Detroit, MI, USA
dDepartment of Medicine, Division of Hematology/Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA
eDepartment of Radiation Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA
Corresponding author. Department of Otolaryngology-Head and Neck Surgery, Wayne State University, 5E University Health Center, 540 East Canfield Avenue, Detroit, MI 48201, USA. Tel.: +1 313 745 4336; fax: +1 313 577 8555.
☆ This work was supported by the National Institute of Health/National Institute of Dental and Craniofacial Research (R21 DE014878).
ABSTRACT