Cetuximab and irinotecan interact synergistically to inhibit the growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice.
OBJECTIVE
Anaplastic thyroid carcinoma (ATC) remains one of the most lethal known human cancers. Targeted molecular therapy with cetuximab, a monoclonal antibody against epidermal growth factor receptor, offers new treatment potentials for patient with ATC. Cetuximab has also been reported to have synergistic effects when combined with irinotecan, a topoisomerase inhibitor. Therefore, we hypothesized that cetuximab and irinotecan would be effective in inhibiting the growth and progression of ATC in a murine orthotopic model.


METHODS
The in vitro antiproliferative effects of cetuximab and irinotecan on ATC cell line ARO were examined. We also studied the in vivo effects of cetuximab and irinotecan on the growth, invasion, and metastasis of orthotopic ATC tumors in nude mice. The in vivo antitumor efficacy of cetuximab/irinotecan combination was also compared with that of doxorubicin.


RESULTS
Cetuximab alone did not show any antiproliferative or proapoptotic effect on this cell line. However, when combined with irinotecan, cetuximab potentiated the in vitro antiproliferative and proapoptotic effect of irinotecan. Cetuximab, irinotecan, and cetuximab/irinotecan combination resulted in 77%, 79%, and 93% in vivo inhibition of tumor growth, respectively. Incidences of lymph node metastasis, laryngeal invasion, and tumor microvessel density were also significantly decreased in these treatment groups. Furthermore, the cetuximab/irinotecan combination was significantly more effective than doxorubicin in inhibiting the growth of orthotopic ATC xenografts.


CONCLUSIONS
Combination therapy with cetuximab/irinotecan inhibits the growth and progression of orthotopic ATC xenografts in nude mice. Given the lack of curative options for patients with ATC, combination therapy with cetuximab and irinotecan treatment warrants further study.
Kim
Seungwon
S
Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Prichard
Christopher N
CN
Younes
Maher N
MN
Yazici
Yasemin D
YD
Jasser
Samar A
SA
Bekele
B Nebiyou
BN
Myers
Jeffrey N
JN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D002448:Cell Adhesion / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D000068818:Cetuximab; D004347:Drug Interactions; D004357:Drug Synergism; D006801:Humans; D000077146:Irinotecan; D008207:Lymphatic Metastasis / Q000517:prevention & control; D008297:Male; D051379:Mice; D008819:Mice, Nude; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077146:Irinotecan; D000068818:Cetuximab; D002166:Camptothecin