Objective: Phase I multicenter study defined the maximal tolerated dose (MTD), dose-limiting toxicity (DLT) and safety profile of capecitabine in combination with preoperative radiation for patients with locally advanced rectal cancer (LARC).

Material and Method: Patients were treated with oral capecitabine (700, 800, 900, 1000, 1100 and 1200 mg/m² twice daily continuously) plus preoperative whole pelvic irradiation (45-46 Gy in 23-25 fractions over 5–6 weeks). Surgery was performed at the median of 42 days after chemoradiation treatment.

Results: Twenty-seven patients were in this trial. Eighteen patients (3 per dose level) had received capecitabine from 700 mg/m² twice daily to the highest dose level of 1200 mg/m² twice daily. There were no grade 3/4 DLTs during dose escalation, a further nine patients were included at the highest capecitabine dose. Two of the twelve patients (16%) receiving capecitabine 1200 mg/m² twice daily developed grade 3 diarrhea and discontinued treatment. There were no other grade 3/4 adverse events. After capecitabine chemoradiation, 24 of 27 patients (89%) received definite surgery. Primary and lymph node down staging occurred in ten patients (42%). Sphincter-sparing surgery was performed in seven patients (26%) and abdominal-perineal resection was performed in 17 patients (63%).

Conclusion: Preoperative capecitabine chemoradiation based on continuous daily capecitabine is very well tolerated in patients with LARC. The authors did not reach the MTD in the present study.

Keywords: Rectal cancer, Chemoradiation, Capecitabine, Radiotherapy