Phase I study of preoperative continuous 5-FU and sorafenib with external radiation therapy in locally advanced rectal adenocarcinoma.

Abstract

3636^ Background: Preoperative treatment with fluoropyrimidine-based chemoradiotherapy is the standard of care in locally advanced rectal cancer (T3, T4 or N1). Sorafenib inhibits of ras/raf, PDFGR and VEGFR with synergistic activity with radiation (RT). This phase I study evaluated the safety and efficacy of sorafenib with infusional 5-FU and RT in patients with locally advanced rectal cancer. Methods: Patients with stage II or III rectal cancer, confirmed by endoscopic ultrasound (EUS) and CT scan, were recruited in 4 cohorts of 3 patients per dose level (DL), with an expansion cohort at the MTD. A 3+3 dose escalation design was used. RT was given in 25 fractions at 1.8Gy (45Gy) day 1-5 at all dose levels. Patients underwent surgery 6-10 weeks following neoadjuvant therapy. Results: 14 patients were enrolled at Moffitt Cancer Center, including 8 females and 6 males with a median age of 55 years (range: 40-72). After observing toxicity in the first cohort (2 patients with G2 and G3 skin toxicity and 1 pa...