Combination Of 5fu-Based Chemoradiation With Egfr Inhibitor Cetuximab And Effect On Pcr Rate In Patients Undergoing Neoadjuvant Treatment In Advanced Rectal Cancer.

623 Background: Neoadjuvant chemoradiation is a standard treatment for advanced rectal cancer patients. Here, we investigate whether treatment combined with the EGFR inhibitor cetuximab could enhance prognosis. Safety and efficacy (pathohistological regression rate, pCR) of chemoradiation in combination with cetuximab were evaluated. Methods: In a single-center phase I/II study patients with adenocarcinoma of the rectum (up to 16 cm above the anal verge) in stage cT3-4, cN0-1, were treated with cetuximab (weekly 250mg/m2, loading dose 400mg/m2) combined with radiotherapy (50,4Gy in 28 fractions) and 5-FU. Maximal tolerated dose of 5FU in combination with cetuximab and radiotherapy was determined in a phase I part (3+3 design; dose level 1: 750 mg/m2 5FU days 1-5 and 29-33; dose level 2: 1000 mg/m2 5FU days 1-5 and 29-33. Surgery was performed between 4 to 6 weeks after combined treatment. pCR rate of tumor cells was determined after surgery. Results: 20 patients were included into the trial, 19 patients received treatment: In the phase I part 2 out of 6 patients in level 2 experienced dose limiting toxicities (thrombocytopenia and diarrhea grade 3). Therefore, dose level 1 was considered safe for further enrollment. All 19 patients received the complete course of radiotherapy (50,4Gy). 15 patients received the complete cetuximab schedule, one patient discontinued after an allergic reaction at the first infusion, 3 patients missed 1 cycle of cetuximab in week 3 or 6. 18 patients continued to surgery. Sphincter preservation surgery was performed in 12 patients (63.2%), R0-resection rate was 100%. pCR grade IV (pCR) was documented in 1 patient (5,5%), grade III in 4 patients and grade I and II in 13 patients. So far no local recurrences occurred, 4 patients died (3 patients due to metastatic disease progression). Conclusions: The MTD of 5FU in combination with radiotherapy and cetuximab was 750mg/m2. Treatment was well tolerated and did not alter surgical management. However, pCR-rate was not elevated compared to standard 5FU-based preoperative chemoradiation. Whether the addition of cetuximab improves prognosis in this group of patient remains unclear. Clinical trial information: 2005-004139-23.