Effect of docetaxel on the surgical tumor microenvironment of head and neck cancer in murine models.
OBJECTIVE
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).


METHODS
Control and experimental series.


METHODS
Academic medical center.


METHODS
BALB/c and severe combined immunodeficiency mice.


METHODS
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.


METHODS
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.
Yoo
George H
GH
Department of Otolaryngology-Head and Neck Surgery, Wayne State University, 5E University Health Center, 4201 St Antoine, Detroit, MI 48201, USA. gyoo@med.wayne.edu
Subramanian
Geetha
G
Piechocki
Marie P
MP
Ensley
John F
JF
Kucuk
Omer
O
Tulunay
Ozlem E
OE
Lonardo
Fulvio
F
Kim
Harold
H
Won
Joshua
J
Stevens
Timothy
T
Lin
Ho-Sheng
HS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D018277:Carcinoma, Mucoepidermoid / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D015552:Injections, Intralesional; D008175:Lung Neoplasms / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010039:Otorhinolaryngologic Neoplasms / Q000473:pathology*; D010865:Pilot Projects; D012468:Salivary Gland Neoplasms / Q000473:pathology; D043823:Taxoids / Q000494:pharmacology* / Q000633:toxicity; D047368:Tumor Burden; D014945:Wound Healing / Q000187:drug effects*
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel