Abstract No. 1234

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. MilosevicRadiation 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)

Hypoxia Tumor Volume

IFP

Characteristic Group NumberSorafenib Dose/

Treatment Response200mg daily 3200mg twice daily 6 Dose limiting toxicity 2400mg 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) 42 died and 2 were alive with disease

85% : 4 year actuarial survival ( 2 deaths at 0.9 and 2.7 years)

ToxicityGrade 3 Acute fatigue 7

lymphopenia 5

diarrhea; 1 chronic diarrhea; dyspareunia 4

Grade 3 Late 3 rectal bleeding and radiation proctitis

4Table 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.