Adjuvant inhibition of the epidermal growth factor receptor after fractionated irradiation of FaDu human squamous cell carcinoma.
OBJECTIVE
Experiments performed by others have shown that inhibition of EGFR before and after single dose irradiation prolonged growth delay and improved local tumour control. This suggests that adjuvant EGFR inhibition can inactivate clonogens that survived irradiation. To test this hypothesis local tumour control was investigated after fractionated radiotherapy and adjuvant EGFR-TK inhibition.


METHODS
FaDu hSCC xenografts were irradiated with 30 fractions in 6 weeks with total doses of 30-100Gy. After the end of fractionated irradiation, BIBX1382BS was administered daily orally over a time period of 75 days. Tumour volumes were determined two times per week, the volume doubling time during adjuvant treatment was calculated for progressing and recurrent tumours. Local tumour control was investigated 120 days after end of irradiation.


RESULTS
Adjuvant BIBX1382BS significantly reduced the tumour growth rate but did not improve local tumour control. The TCD(50) values were 66.1Gy (95% C.I.: 59; 73Gy) after adjuvant BIBX1382BS treatment and 67.9Gy (61; 75Gy) for control tumours (P=0.9).


CONCLUSIONS
These data indicate that, although growth of recurrent tumour cells after irradiation is dependent on the EGFR pathway, tumour cells retain their clonogenic potential despite of EGFR inhibition. The results imply also that a decreased tumour growth rate does not necessarily allow conclusions on enhanced inactivation of clonogenic cells when antiproliferative drugs are combined with radiation.
Krause
M
M
Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Fetscherstr, 74, 01307 Dresden, Germany.
Hessel
F
F
Zips
D
D
Hilberg
F
F
Baumann
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy* / Q000662:veterinary; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000662:veterinary; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental; D009930:Organic Chemicals / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
D000970:Antineoplastic Agents; C423062:BIBX 1382BS; D009930:Organic Chemicals; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases