Experimental Therapeutics Poster Discusson on Tumor Targeting

Tuesday, October 18, 2005 3:30 PM-5:00 PM Room No. 603
Chair(s): Stratford, Ian; Greco, Olga

(PD010) C225-induced enhancement of tumor radioresponse: Influence of timing of C225 administration.

Milas, Luka1, Koto, Masashi*,1, Valdecanas, David1, Mason, Kathy1, Hunter, Nancy1, Fan, Zhen2, Fang, Fu-Min1, Ang, Kian3, 1 Experimental Radiation Oncology and Division of Radiation Oncology, Houston, TX, USA2 Experimental Therapeutics, Houston, TX, USA3 Division of Radiation Oncology, Houston, TX, USA

ABSTRACT- Background: Our earlier studies showed that the C225 anti-EGFR antibody strongly enhances single dose radiation-induced growth delay and cure of A431 human tumor xenografts (Clin Cancer Res, 6:701-708, 2000 and Int J Radiat Oncol Biol Phys, 51(2): 474-477, 2001). The present study tested whether this effect of C225 depends on timing of C225 in relation to single dose or fractionated irradiation. Materials and Methods: A431 tumor xenografts growing in the leg of nude mice were exposed to single dose or fractionated irradiation when 8 mm in diameter. Single or multiple injections of 1mg/mouse were given ip at different times before, during or following tumor irradiation. The endpoints of the treatments were tumor growth delay or tumor cure (TCD50 = radiation dose yielding 50% tumor cure). Results: A single dose of C225 given between 6 days before and 7 days after 18 Gy single dose irradiation enhanced tumor radioresponse to a similar extent, with enhancement factors (EF) 2.36 to 3.63. A TCD50 study, where tumors were given a range of single doses (10 to 70 Gy) provided similar results. C225 administered 3 h before plus 3 and 6 days after radiation reduced the control TCD50 value of 49.4 (44.9-55.9) Gy to 23.6 (20.8-26.2) Gy (EF = 2.09), and C225 administered 1, 4 and 5 days after radiation reduced it to 16.9 (9.9-20.3) Gy. (EF = 2.92). In the study with fractionated irradiation (20 Gy given in 2 Gy fractions twice daily for 5 days), C225 was administered (a) before and during, (b) before, during and after, (c) only after fractionated radiotherapy. All three schedules enhanced tumor radioresponse; however, while schedules a and c were similarly effective (EFs = 3.91 and 4.74, respectively), the schedule b was the most effective, EF being 6.62. Conclusions: C225 was highly effective in enhancing A431 tumor radioresponse to both single and fractionated irradiation. The effect appears to be the strongest when C225 is given before, during and after radiotherapy. [Supported by NIH Research Grant PO1 CA06294]

Key words: C225, EGFR, radiation

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2005 RRS