Preoperative chemoradiotherapy with capecitabine and oxaliplatin in locally advanced rectal cancer. A phase I-II multicenter study of the Dutch Colorectal Cancer Group.

Background: We studied the maximum tolerated dose (MTD) and efficacy of oxaliplatin added to capecitabine and radiotherapy (Capox-RT) as neoadjuvant therapy for rectal cancer.

Methods: T3-4 rectal cancer patients received escalating doses of oxaliplatin (day 1 and 29) with a fixed dose of capecitabine of 1000 mg/m(2) twice daily (days 1-14, 25-38) added to RT with 50.4 Gy and surgery after 6-8 weeks. The MTD, determined during phase I, was used in the subsequent phase II, in which R0 resection rate (a negative circumferential resection margin) was the primary end point.

Results: Twenty-one patients were evaluable. In the phase I part, oxaliplatin at 85 mg/m(2) was established as MTD. In phase II, the main toxicity was grade III diarrhea (18%). All patients underwent surgery, and 20 patients had a resectable tumor. An R0 was achieved in 17/21 patients, downstaging to T0-2 in 7/21 and a pCR in 2/21.

Conclusion: Combination of Capox-RT has an acceptable acute toxicity profile and a high R0 resection rate of 81% in locally advanced rectal cancer. However the pCR rate was low.