title: Effect of combined irradiation and EGFR/Erb-B inhibition with BIBW 2992 on proliferation and tumour cure in cell lines and xenografts.
abstract: OBJECTIVE
  In previous experiments an enhanced anti-proliterative effect of the EGFR/ErbB tyrosine kinase inhibitor (TKI) BIBW 2992 with single dose irradiation was observed in FaDu tumour xenografts. Aim of the present experiment was to determine if this effect can also be seen in combination with a fractionated radiotherapy. Secondly we investigate the efficacy of BIBW 2992 on local tumour control for UT-SCC-15.
  
  
  METHODS
  Tumour pieces of FaDu, UT-SCC-14, A431, UT-SCC-15 (squamous cell carcinomas) and A7 (glioma) tumour models were transplanted onto the right hind leg of NMRI (nu/nu) nude mice. For evaluation of tumour growth mice were either treated daily orally with BIBW 2992 (30 mg/kg body weight), or carrier up to a final tumour size of 15 mm or with a fractionated radiotherapy (15f/15d, 30 Gy) with simultaneous application of BIBW 2992 or carrier. For local tumour control UT-SCC-15 tumours were treated with a fractionated radiotherapy (30f/6weeks) or received 30f/6 weeks in combination with daily orally BIBW 2992 (22.5 mg/kg b.w.) during RT.
  
  
  RESULTS
  A significant effect on tumour growth time was observed in all tumour models for BIBW 2992 application alone. However, substantial intertumoural heterogeneity could be seen. In the UT-SCC-14, UT-SCC-15 and A431 tumour models a total regression of the tumours and no recurrence during treatment time (73 days) were determined where as for the A7 tumour only a slight effect was noticeable. For the combined treatment of fractionated radiotherapy (15f/15d) and BIBW 2992 administration a significant effect on tumour growth time was seen compared to irradiation alone for A7, UT-SCC-15 and A431 (ER 1.2 - 3.7), this advantage could not be demonstrated for FaDu and UT-SCC-14. However, the local tumour control was not altered for the UT-SCC-15 tumour model when adding BIBW 2992 to fractionated irradiation (30f/6weeks).
  
  
  CONCLUSIONS
  A heterogeneous effect on tumour growth time of BIBW 2992 alone as well as in combination with fractionated irradiation could be demonstrated for all tumour models. However, the significant effect on tumour growth time did not translate into an improvement of local tumour control for the UT-SCC-15 tumour model.
authors.affiliation: Department of Radiation Oncology, UniversityHospital C.G. Carus, Fetscherstr. 74, 01307, Dresden, Germany. kristin.gurtner@uniklinikum-dresden.de.|OncoRay - National Centerfor Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, TechnischeUniversität and Helmholtz-Zentrum Dresden -Rossendorf, Dresden, Germany. kristin.gurtner@uniklinikum-dresden.de.
authors.forename: Kristin
authors.initials: K
authors.lastname: Gurtner
authors.affiliation: Department of Radiation Oncology, UniversityHospital C.G. Carus, Fetscherstr. 74, 01307, Dresden, Germany. nadja.ebert@uniklinikum-dresden.de.|OncoRay - National Centerfor Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, TechnischeUniversität and Helmholtz-Zentrum Dresden -Rossendorf, Dresden, Germany. nadja.ebert@uniklinikum-dresden.de.
authors.forename: Nadja
authors.initials: N
authors.lastname: Ebert
authors.affiliation: Department of Radiation Oncology, UniversityHospital C.G. Carus, Fetscherstr. 74, 01307, Dresden, Germany. Dorothee.Pfitzmann@uniklinikum-dresden.de.|OncoRay - National Centerfor Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, TechnischeUniversität and Helmholtz-Zentrum Dresden -Rossendorf, Dresden, Germany. Dorothee.Pfitzmann@uniklinikum-dresden.de.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Pfitzmann
authors.affiliation: Department of Radiation Oncology, UniversityHospital C.G. Carus, Fetscherstr. 74, 01307, Dresden, Germany. wolfgang.eicheler@mailbox.tu-dresden.de.|OncoRay - National Centerfor Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, TechnischeUniversität and Helmholtz-Zentrum Dresden -Rossendorf, Dresden, Germany. wolfgang.eicheler@mailbox.tu-dresden.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eicheler
authors.affiliation: Department of Radiation Oncology, University Hospital Tuebingen, Tuebingen, Germany. Daniel.Zips@med.uni-tuebingen.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zips
authors.affiliation: Department of Radiation Oncology, UniversityHospital C.G. Carus, Fetscherstr. 74, 01307, Dresden, Germany. Michael.Baumann@uniklinikum-dresden.de.|OncoRay - National Centerfor Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, TechnischeUniversität and Helmholtz-Zentrum Dresden -Rossendorf, Dresden, Germany. Michael.Baumann@uniklinikum-dresden.de.|German Cancer consortium (DKTK) Dresden and German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany. Michael.Baumann@uniklinikum-dresden.de.|Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany. Michael.Baumann@uniklinikum-dresden.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
authors.affiliation: Department of Radiation Oncology, UniversityHospital C.G. Carus, Fetscherstr. 74, 01307, Dresden, Germany. Mechthild.Krause@uniklinikum-dresden.de.|OncoRay - National Centerfor Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, TechnischeUniversität and Helmholtz-Zentrum Dresden -Rossendorf, Dresden, Germany. Mechthild.Krause@uniklinikum-dresden.de.|German Cancer consortium (DKTK) Dresden and German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany. Mechthild.Krause@uniklinikum-dresden.de.|Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany. Mechthild.Krause@uniklinikum-dresden.de.
authors.forename: Mechthild
authors.initials: M
authors.lastname: Krause
mesh_terms: D000077716:Afatinib; D000818:Animals; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy / Q000379:methods*; D019583:Dose Fractionation, Radiation; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000532:radiotherapy*; D011799:Quinazolines / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
chemical_list: D011799:Quinazolines; D011838:Radiation-Sensitizing Agents; D000077716:Afatinib; C512478:EGFR protein, human; D066246:ErbB Receptors