Neoadjuvant chemoradiation therapy with capecitabine (X) plus cetuximab (C), and external beam radiotherapy (RT) in locally advanced rectal cancer (LARC): ABCSG trial R03

Abstract

4109 Background: Pre-operative chemoradiation is a standard treatment for LARC. X and C are synergistic with radiotherapy and active in colorectal neoplasms. This phase II multicenter trial was designed to assess the feasability and tolerability of a preoperative combination of X, C, plus RT in patients with LARC. Secondary endpoints were downstaging-rate and induction of complete pathological response (CPR). Only patients (pts.) with MRT-documented T3/T4-tumours were included. Methods: Pts. with potentially resectable cT4 or cT3 LARC (lower/mid rectum) were enrolled. Chemoradiotherapy consisted of X (825mg/sqm twice daily on RT-days weeks 1–4), C (400mg/sqm loading dose once per week, 200mg/sqm weekly x 4) and pelvic RT 3D conformation technique (1.8Gy/day, 45Gy total). Surgery was performed 28–42 days after completion of RT. Results: 31 pts. were enrolled, median age was 61 years (range 41 to 80), PS 0: 22 pts. (71%), PS 1: 8 pts. (26%), PS 2: 1 pt. (3%). 21 pts. (68%) presented with cT4, 10 pts. (32%) with cT3 tumors. 25 pts. (81%) had positive lymph nodes (LN) by imaging, 2 pts. were LN-negative, 4 pts. (13%) are not evaluable for N-stage. 28 pts (90%) are available for evaluation of toxicity and efficacy. Treatment with X and C plus RT was well tolerated, in only 4 pts. grade 3 toxicity was observed: acneiform skin rash 2 pts (7%), diarrhea 3 pts (11%), 1 pt. (4%) suffered from grade 4 diarrhea. Median dose intensity of X and C was >95% during the entire treatment period. Tumor downstaging was observed in 14 pts. (50%) total, 12/19 (63%) T4 tumours and 2/9 (22%) T3 tumors responded. While no patient achieved a CPR, in 14 pts. a lymph node clearing (ypN0) was observed. Conclusions: The combination of capecitabine and cetuximab plus radiotherapy is a well tolerated preoperative treatment regime for LARC (cT3/4). The main toxicity consisted of diarrhea. The combination is effective in the primary tumor as well as in the lymph nodes, both with possible impact on therapy outcome. No significant financial relationships to disclose.