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Open Access 01-12-2014 | Research

Effect of combined irradiation and EGFR/Erb-B inhibition with BIBW 2992 on proliferation and tumour cure in cell lines and xenografts

Authors: Kristin Gurtner, Nadja Ebert, Dorothee Pfitzmann, Wolfgang Eicheler, Daniel Zips, Michael Baumann, Mechthild Krause

Published in: Radiation Oncology | Issue 1/2014

Abstract

Background and purpose

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.

Material and 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).

Conclusion

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.

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Title: Effect of combined irradiation and EGFR/Erb-B inhibition with BIBW 2992 on proliferation and tumour cure in cell lines and xenografts
Authors: Kristin Gurtner
Nadja Ebert
Dorothee Pfitzmann
Wolfgang Eicheler
Daniel Zips
Michael Baumann
Mechthild Krause
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Radiation Oncology / Issue 1/2014
Electronic ISSN: 1748-717X
DOI: https://doi.org/10.1186/s13014-014-0261-z

At a glance: The STEP trials

Springer Medicine

Effect of combined irradiation and EGFR/Erb-B inhibition with BIBW 2992 on proliferation and tumour cure in cell lines and xenografts

Abstract

Background and purpose

Material and methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background and purpose

Material and methods

Results

Conclusion

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