EGFR antibody-supplemented TPE-chemotherapy. Preclinical investigations to a novel approach for head and neck cancer induction treatment.
Recent studies on polychemotherapy of head and neck cancer have shown an improved remission rate on adding taxanes to the standard cytotoxic drugs cisplatin and 5-fluorouracil (5-FU). Moreover, for enhancing the response rate of chemotherapy today, a series of biological response modifiers are of interest including modulators of the epidermal growth factor receptor (EGFR). Therefore we investigated whether the addition of monoclonal antibodies against the EGFR could enhance the response rate of cisplatin, 5-FU and docetaxel. Squamous cell cancer lines were transplated on nude mice. After tumors had begun to grow, they were treated either with cisplatin, 5-FU and docetaxel alone or in combination with escalating doses of a humanized monoclonal anti-EGFR antibody. Comparing with controls, docetaxel alone as well as the combination of docetaxel, cisplatin and 5-FU resulted in a significant tumor growth delay. The antibody alone also slowed down the tumor growth significantly at each concentration. Nevertheless, neither chemotherapy agents nor antibody alone yielded complete tumor remissions over an observation period up to 6 weeks. Only the combination of cisplatin, 5-FU, docetaxel and the antibody resulted in highly significant complete tumor remissions. Therefore we can show for the first time that the effect of TPF, which is now used as a novel Phase II protocol for induction chemotherapy in head and neck cancer, could be highly significantly enhanced through the addition of anti-EGFR antibodies. Because we did not observe an increased toxicity in the animal experiments, TPF/anti-EGFR therapy may define a new strategy in the induction treatment of head and neck carcinomas.
Department of Otorhinolaryngology, School of Medicine, J.W. Goethe University, 60590 Frankfurt, Germany. knecht@em.uni-frankfurt.de
Rainald
R
Knecht
Silke
S
Peters
Christine
C
Solbach
Mehran
M
Baghi
Wolfgang
W
Gstöttner
Markus
M
Hambek
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D004195:Disease Models, Animal; D000077143:Docetaxel; D066246:ErbB Receptors / Q000276:immunology*; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D043823:Taxoids / Q000008:administration & dosage; D014062:Tongue Neoplasms; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D043823:Taxoids; D000077143:Docetaxel; D066246:ErbB Receptors; D002945:Cisplatin; D005472:Fluorouracil