Abstract No A Phase I/II Study of the Angiogenesis Inhibitor Sorafenib in Cervical Cancer Patients Treated with Radiotherapy Naz Chaudary A. Fyles, C. Townsley, K. Han, R.P. Hill, S. Kim, W. Levin, H. MacKay, L. Manchul, I. Yeung, A. Oza, M. Milosevic Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada; and Departments of Radiation Oncology and Medical Biophysics, University of Toronto, Toronto, Canada Poster #12

AIM: To examine the efficacy and toxicity of sorafenib in patients with cervix cancer receiving RT and cisplatin chemotherapy (RTCT) HypoxiaTumor Volume IFP Characteristic GroupNumber Sorafenib Dose/ Treatment Response 200mg daily 3 200mg twice daily6 Dose limiting toxicity2 400mg twice daily 4 Grade 3 anal fissure 1 Locally infiltrative stage IIIB, rapid regression, vesico vaginal fistula 1 Tumor Control DFS (disease free) PS (persistent pelvic disease) RD (recurrent disease) DFS (at last follow up ) 8 PD (at completion of treatment- died) 1 RD (1 primary site and pelvic LN (died); 1 pelvic LN alone; 2 distant met sites) 4 2 died and 2 were alive with disease 85% : 4 year actuarial survival ( 2 deaths at 0.9 and 2.7 years) Toxicity Grade 3 Acute fatigue 7 lymphopenia 5 diarrhea; 1 chronic diarrhea; dyspareunia 4 Grade 3 Late 3 rectal bleeding and radiation proctitis 4 Table 1: Clinical Outcomes- detailed table on poster #12 Phase I/II Study Schema

Sorafenib reduces tumor perfusion and/or vascular permeability

Sorafenib reduces tumor infiltration by myeloid cells that can contribute to vascular persistence and new vessel formation during RT The combination of RTCT and sorafenib was well tolerable similar to RTCT alone. Mechanism: Sorafenib offsets the RT resistance through an of hypoxia, by neutrophil recruitment to the tumor = allowing better treatment response.