Carcinomas unresponsive to either cisplatinum or anti-EGFR therapy can be growth inhibited by combination therapy of both agents.
BACKGROUND
Previously we demonstrated that the antitumor efficacy of monoclonal antibodies against the EGFR (epidermal growth factor receptor) of human tumor xenografts mainly depends on the EGFR content of tumors rather than on the tumors' entity. In this study we wanted to elucidate whether the described cumulative effect of cisplatin and Anti-EGFR therapy also depends on the EGFR expression.


METHODS
Xenotransplanted carcinomas with different EGFR levels were treated with monoclonal antibodies against the EGFR (EMD 72000 and EMD 55900), cisplatinum and a combination of both.


RESULTS
Each monoclonal antibody alone led to an EGFR-dependent significant tumor growth reduction. Cisplatinum alone had no growth inhibitory effects on tumors with high content in contrast to those with low EGFR content. The combination of antibodies with cisplatinum resulted in an EGFR-independent tumor growth inhibition which was stronger than observed in the case of monotherapy.


CONCLUSIONS
The obtained results may address upcoming phase I/II trials to use Anti-EGFR/Cisplatinum therapy regardless of the EGFR content of tumors.
Knecht
R
R
Department of Otorhinolaryngology, University of Frankfurt, Medical School, 60590 Frankfurt/M., Germany.
Peters
S
S
Adunka
O
O
Strebhardt
K
K
Gstoettner
W
W
Hambek
M
M
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004357:Drug Synergism; D066246:ErbB Receptors / Q000096:biosynthesis / Q000276:immunology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D002945:Cisplatin