Intratumoral delivery of docetaxel enhances antitumor activity of Ad-p53 in murine head and neck cancer xenograft model.
OBJECTIVE
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.


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 x 10(10) viral particles per injection), (c) docetaxel (1 mg/kg per injection), and (d) combination of Ad-p53 (1 x 10(10) 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.


CONCLUSIONS
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.
Yoo
George H
GH
Department of Otolaryngology-Head and Neck Surgery, Wayne State University, 5E University Health Center, 540 East Canfield Avenue, Detroit, MI 48201, USA. gyoo@med.wayne.edu
Subramanian
Geetha
G
Ezzat
Waleed H
WH
Tulunay
Ozlem E
OE
Tran
Vivian R
VR
Lonardo
Fulvio
F
Ensley
John F
JF
Kim
Harold
H
Won
Joshua
J
Stevens
Timothy
T
Zumstein
Louis A
LA
Lin
Ho-Sheng
HS
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D000077143:Docetaxel; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D015552:Injections, Intralesional; D051379:Mice; D043823:Taxoids / Q000008:administration & dosage*; D016159:Tumor Suppressor Protein p53 / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; D000077143:Docetaxel