title: Concomitant chemoirradiation with vinorelbine and gefitinib induces additive effect in head and neck squamous cell carcinoma cell lines in vitro.
abstract: OBJECTIVE
  The study was performed to measure the radiosensitizing effect of vinorelbine together with gefitinib in head and neck squamous cell carcinoma (HNSCC) cell lines in vitro.
  
  
  METHODS
  Three recently established HNSCC cell lines, originating from larynx and oral cavity tumors, were tested in this study. Vinorelbine concentration of 0.5 nM was used, corresponding to the IC(70) value of cell lines. Gefitinib concentrations of 0.10-0.35 microM were used, corresponding to IC(70)- and IC(50)-values of each cell line, causing 30% and 50% inhibition in clonogenic survival, respectively. Vinorelbine was added to the medium and the cells were plated in 96-well culture plates in this solution. 24h later the cells were irradiated in plates with 4 MeV photons generated by a linear accelerator, producing radiation doses 0.75-7.5 Gy. Immediately after irradiation the desired concentrations of gefitinib were added, whereafter the plates were incubated at 37 degrees C with 5% CO(2). After four weeks, the number of wells containing coherent living colonies, consisting of 32 cells or more, was counted. The plating efficiency was calculated and the fraction survival data were fitted to the linear quadratic model, F=exp[-(alphaD+betaD(2))]. The area under the survival curve (AUC) value was obtained with numerical integration. ErbB receptor expression of the HNSCC cell lines was analyzed by Western blotting.
  
  
  RESULTS
  The growth-inhibitory effect of simultaneous vinorelbine and gefitinib concomitant with radiation was supra-additive in cell line UT-SCC-33 and additive in cell lines UT-SCC-19A and -34.
  
  
  CONCLUSIONS
  HNSCC is in vitro constantly sensitive to the combination of vinorelbine and gefitinib, which have together an additive effect in concomitant use with irradiation. Further studies are warranted to evaluate the concomitant use of vinorelbine and gefitinib with irradiation in clinical studies. In addition, both drugs are available in an oral formulation allowing effortless administration schedules.
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Turku University Central Hospital, Finland.
authors.forename: Kaisa
authors.initials: K
authors.lastname: Erjala
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Maria
authors.initials: M
authors.lastname: Sundvall
authors.forename: Jarmo
authors.initials: J
authors.lastname: Kulmala
authors.forename: Klaus
authors.initials: K
authors.lastname: Elenius
authors.forename: Reidar
authors.initials: R
authors.lastname: Grénman
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004357:Drug Synergism; D066246:ErbB Receptors / Q000032:analysis / Q000037:antagonists & inhibitors*; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000628:therapy*; D006801:Humans; D011799:Quinazolines / Q000008:administration & dosage*; D020893:Receptor, ErbB-3 / Q000032:analysis; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D011799:Quinazolines; D014747:Vinblastine; D066246:ErbB Receptors; D020893:Receptor, ErbB-3; D000077235:Vinorelbine; D000077156:Gefitinib