Concurrent use of vinorelbine and gefitinib induces supra-additive effect in head and neck squamous cell carcinoma cell lines.
OBJECTIVE
Squamous cell carcinoma of the head and neck (HNSCC) remains a clinical challenge because of the high rate of locoregional disease recurrence. Standard treatment includes surgery, radiation, chemoradiation or a combination of these approaches. New therapies are needed to achieve improved survival, quality of life and organ function in these patients. A novel molecular targeted therapy incorporated into our current treatment strategies may have a significant role in the treatment of HNSCC. The aim of this study was to evaluate the sensitivity of HNSCC cell lines to vinorelbine combined with gefitinib in vitro.


METHODS
Six recently established cell lines were used: UT-SCC-9, -11, -19A, -29 and -34 (laryngeal SCC) and UT-SCC-33 (oral cavity SCC). Chemosensitivity was tested using the 96-well plate clonogenic assay. The vinorelbine concentrations used varied between 0.4 and 1.0 nM and the gefitinib concentrations varied between 0.05 and 1.6 muM. Survival data were fitted to the LQ model, and the area under the curve (AUC) value was obtained with numerical integration. The type of interaction was determined by comparing the AUC ratio of the two drugs to the survival fraction (SF) of gefitinib alone.


RESULTS
In the current study the combination of vinorelbine and gefitinib had a clear supra-additive or additive cytotoxic effect on the HNSCC cell lines.


CONCLUSIONS
This finding is encouraging as a proof of the possible benefit of combing an EGFR targeting compound with a cell cycle specific drug and warrants further studies of available combinations in vitro.
Erjala
Kaisa
K
Department of Otorhinolaryngology, Head and Neck Surgery, Turku University Central Hospital, 20520 Turku, Finland.
Raitanen
Misa
M
Kulmala
Jarmo
J
Grénman
Reidar
R
D000704:Analysis of Variance; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011799:Quinazolines / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
D000972:Antineoplastic Agents, Phytogenic; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D014747:Vinblastine; D000077235:Vinorelbine; D000077156:Gefitinib