Concurrent cetuximab, cisplatin, and radiation for squamous cell carcinoma of the head and neck in vitro.
OBJECTIVE
For locoregionally advanced HNSCC, chemoradiotherapy with cisplatin or another platinum compound is considered as one of the standard treatment regimes. Cisplatin has improved the loco-regional control, but also increased especially the acute side effects. Cetuximab blocks ligand binding and receptor activation by binding to the extracellular domain of the EGFR. The blockade of EGFR signaling in combination with cytotoxic drugs or with radiotherapy could be a novel effective management with a relatively favourable toxicity for HNSCC. In the present study we have examined in vitro a potentially novel effective management for HNSCC, cetuximab combined with cisplatin and radiotherapy.


METHODS
Seven head and neck SCC cell lines were studied. Cetuximab concentrations of 0.22-8.20 nM and cisplatin concentrations of 0.038-0.220 microg/ml were used. In order to test the concurrent use of cetuximab, cisplatin and radiation, the cells were treated with the desired drug concentrations immediately after irradiation, plated into 96-well culture plates, and incubated for 4 weeks. The number of positive wells was counted. The PE was calculated and fraction survival data were fitted to the LQ model. AUC value was obtained with numerical integration. The types of interaction were analyzed.


RESULTS
Cetuximab and cisplatin constantly induced an additive or supra-additive effect when combined with irradiation in the seven HNSCC cell lines tested.


CONCLUSIONS
We evaluated concurrent cetuximab, cisplatin, and radiation for HNSCC cell lines. Preliminary efficacy results are encouraging, and further development of this targeted combined modality paradigm is warranted.
Zhang
Na
N
Department of Otorhinolaryngology-Head and Neck Surgery, Turku University Hospital, Turku, Finland.
Erjala
Kaisa
K
Kulmala
Jarmo
J
Qiu
Xueshan
X
Sundvall
Maria
M
Elenius
Klaus
K
Grénman
Reidar
R
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000528:radiation effects*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D000068818:Cetuximab; D002945:Cisplatin / Q000494:pharmacology; D003131:Combined Modality Therapy; D003470:Culture Media; D004357:Drug Synergism; D066246:ErbB Receptors / Q000032:analysis / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011336:Probability; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003470:Culture Media; D066246:ErbB Receptors; D000068818:Cetuximab; D002945:Cisplatin