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Effect of Docetaxel on the Surgical Tumor Microenvironment of Head and Neck Cancer in Murine Models
George H. Yoo, MD;
Geetha Subramanian, MD;
Marie P. Piechocki, PhD;
John F. Ensley, MD;
Omer Kucuk, MD;
Ozlem E. Tulunay, MD;
Fulvio Lonardo, MD;
Harold Kim, MD;
Joshua Won;
Timothy Stevens;
Ho-Sheng Lin, MD
Arch Otolaryngol Head Neck Surg. 2008;134(7):735-742.
Objectives To identify the antitumor activity and wound-healing effect of docetaxel delivered in the surgical tumor microenvironment of head and neck squamous cell carcinoma (HNSCC).
Design Control and experimental series.
Setting Academic medical center.
Subjects BALB/c and severe combined immunodeficiency mice.
Intervention Intrawound (IW) docetaxel therapy was tested in 3 HNSCC xenograft and 2 taxane-resistant models. Intratumoral (IT) docetaxel therapy was further tested in the 2 taxane-resistant models.
Main Outcome Measures Tumor size, survival, and wound toxic effects were measured. The effect of docetaxel on various factors involved in wound healing and tumor growth within the surgical tumor microenvironment was also analyzed.
Results In a pilot study using BALB/c mice, IW docetaxel therapy was not associated with problems in wound healing. Using the HN6, HN12, and HN30 HNSCC xenograft model, IW docetaxel prevented tumor growth and improved survival when compared with controls. No local or systemic toxic effect or wound-healing problem was noted. Using taxane-resistant xenograft lung cancer (H460/T800) and syngeneic salivary cancer (BALB/c mucoepidermoid carcinoma) models, IW therapy did not delay tumor growth. An antitumor effect was detected with repeated docetaxel injections in the H460/T800 taxane-resistant model but not in the BALB/c mucoepidermoid carcinoma model. Docetaxel inhibited the expression of growth factors and receptors in tumor cells; however, it did not inhibit the level of wound-healing growth factors in the surgical tumor microenvironment.
Conclusions These preclinical results support further testing of IW docetaxel treatment in HNSCC. Docetaxel appears to exert antitumor activity without affecting factors involved in wound healing in the tumor microenvironment.
Author Affiliations: Department of Otolaryngology–Head and Neck Surgery (Drs Yoo, Subramanian, Piechocki, Ensley, Kucuk, Tulunay, and Lin and Messrs Won and Stevens), Division of Hematology/Oncology, Department of Medicine (Drs Ensley and Kucuk), and Department of Radiation Oncology (Dr Kim), Karmanos Cancer Institute, Department of Pathology, Wayne State University (Dr Lonardo), and Department of Surgery, John D. Dingell Veterans Affairs Medical Center (Dr Lin), Detroit, Michigan.
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