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

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 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.

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.

• Authors: George H Yoo, Geetha Subramanian, Waleed H Ezzat, Ozlem E Tulunay, Vivian R Tran, Fulvio Lonardo, John F Ensley, Harold Kim, Joshua Won, Timothy Stevens, Louis A Zumstein, Ho-Sheng Lin
• Journal: American journal of otolaryngology (Am J Otolaryngol) 2010 Mar-Apr Vol. 31 Issue 2 Pg. 78-83 ISSN: 1532-818X [Electronic] United States
• PMID: 20015717 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright (c) 2010 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Taxoids
• Tumor Suppressor Protein p53
• Docetaxel

Topics

• Adenoviridae (genetics)
• Animals
• Antineoplastic Agents (administration & dosage)
• Carcinoma, Squamous Cell (drug therapy)
• Docetaxel
• Head and Neck Neoplasms (drug therapy)
• Injections, Intralesional
• Mice
• Taxoids (administration & dosage)
• Tumor Suppressor Protein p53 (administration & dosage)
• Xenograft Model Antitumor Assays