C225 antiepidermal growth factor receptor antibody enhances tumor radiocurability.
OBJECTIVE
Overexpression of epidermal growth factor receptor (EGFR) has been correlated with tumor resistance to radiation. Blockade of EGFR with C225 anti-EGFR antibody was previously shown to synergistically enhance radiation-induced tumor growth delay. The purpose of this study was to assess whether C225 can increase tumor cure by radiation.


METHODS
Nude mice bearing 8-mm-diameter A431 tumor xenografts in the hind leg were treated with C225 antibody, graded single doses of local tumor irradiation, or both. C225 was given i.p. at a dose of 1 mg/mouse 6 h before irradiation or 6 h before and 3 plus 6 days after irradiation. Tumor cure was the treatment endpoint assessed by the TCD(50) assay 120 days after treatment. The onset of recurrences of tumors not cured was also determined.


RESULTS
C225 antibody increased the antitumor effects of radiation by reducing TCD(50) values and delaying tumor recurrences. Tumor radiocurability was enhanced by a factor of 1.18 by a single dose and by a factor of 1.92 by three doses of C225. Likewise, the appearance of tumor recurrences was delayed by a factor of 1.37 by a single dose and by a factor of 2.13 by three doses of C225.


CONCLUSIONS
The data presented here demonstrate that C225 can increase tumor radiocurability and delay the appearance of recurrences of tumors not cured by radiation treatment.
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Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA.
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Milas
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068818:Cetuximab; D004307:Dose-Response Relationship, Radiation; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009369:Neoplasms / Q000737:chemistry / Q000532:radiotherapy*; D011853:Radiobiology; D011879:Radiotherapy Dosage; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D066246:ErbB Receptors; D000068818:Cetuximab