Preoperative oxaliplatin (O), capecitabine (X), and external beam radiotherapy (RT) in patients (pts) with newly diagnosed, primary operable, locally advanced rectal cancer (LARC)

Abstract

14527 Background: Local recurrence after surgery is a cause of treatment failure and relapse in pts with LARC. Preoperative RT decreases local recurrence but not distant spread. X and O are both highly active chemotherapies for advanced colorectal cancer, particularly in combination, and both are radiosensitizers. Therefore, the addition of X and O to preoperative RT should improve efficacy in terms of local control and prevention of metastases. Methods: This study investigated the efficacy (rate of downstaging) and safety of preoperative chemoradiation in pts with LARC (of lower and middle rectum), T3NxM0 staged by MRT. RT was administered for 5 weeks, 5 days/week, 1.8 Gy/fraction, total dose 45 Gy, 3D conformation technique, in combination with O 50 mg/m2 intravenously on days 1, 8, 15, and 22, and oral X 825 mg/m2 twice a day on RT-days during weeks 1–4. Surgery was performed 14–28 days after completion of RT. Results: 59 pts were enrolled (19 female, 40 male); median age 61 years (range 34–76), 100% of pts are evaluable for efficacy and toxicity. 41 patients had comorbidities: 16 cardiac, 3 hepatic, 6 diabetes, 1 neurological/psychological, 49 others. Tumor downstaging was observed in 53% of pts (23 T2, 2 T1, 6 T0). 5 pts withdrew because of adverse events. 28 pts (47%) experienced grade 1 neurotoxicity and 5 pts (8%) had grade 2 neurotoxicity. The most frequent grade 3/4 NCI-CTC adverse event was diarrhea: 5/59 pts (8%). Total O and X doses received were 90% and 93% of the planned doses, respectively. The main reason for chemotherapy dose reduction was diarrhea occurring during the 3rd-4th week of treatment. Per-protocol therapy was terminated for 8 pts due to interruption of RT for more than 3 days or adverse events such as diarrhea and nausea (total dose received 25.2–34.2 Gy). Conclusions: These results demonstrate that preoperative O and X in combination with RT is feasible in pts with LARC, and comparable with 5-FU. As expected, the only clinically relevant toxicity was diarrhea, and dose intensity of both chemotherapeutic agents and RT was high. [Table: see text]