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Phase I/II Trial of Capecitabine, Oxaliplatin, and Radiation for Rectal Cancer

Claus Rödel, Gerhard. G. Grabenbauer, Thomas Papadopoulos, Werner Hohenberger, Hans-Joachim Schmoll, Rolf Sauer

From the Departments of Radiation Therapy and Surgery and Institute of Pathology, University of Erlangen, Erlangen; and Department of Internal Medicine and Hematology/Oncology, University of Halle-Wittenberg, Halle, Germany.

Address reprint requests to Claus Rödel, MD, Department of Radiotherapy, University of Erlangen, Universitätsstr 27, 91054 Erlangen, Germany; email: claus.roedel{at}strahlen.med.uni-erlangen.de.

Purpose: The purpose of this study was to establish the feasibility and efficacy of preoperative radiotherapy (RT) with concurrent capecitabine and oxaliplatin (XELOX-RT) in patients with rectal cancer.

Patients and Methods: Thirty-two patients with locally advanced (T3/T4) or low-lying rectal cancer received preoperative RT (total dose, 50.4 Gy). Capecitabine was administered concurrently at 825 mg/m² bid on days 1 to 14 and 22 to 35, with oxaliplatin starting at 50 mg/m² on days 1, 8, 22, and 29 with planned escalation steps of 10 mg/m². End points of the phase II study included downstaging, histopathologic tumor regression, resectability of T4 disease, and sphincter preservation in patients with low-lying tumors.

Results: Dose-limiting grade 3 gastrointestinal toxicity was observed in two of six patients treated with 60 mg/m² of oxaliplatin. Thus, 50 mg/m² was the recommended dose for the phase II study. Toxicities observed at this dose level were generally mild, with only two cases of short-lived grade 3 diarrhea. Myelosuppression, mainly leukopenia, was restricted to grade 2 in 19% of patients. T-category downstaging was achieved in 17 (55%) of 31 operated patients, and 68% of patients had negative lymph nodes. Pathologic complete response was found in 19% of the resected specimens. Radical surgery with free margins could be performed in 79% of patients with T4 disease, and 36% of patients with tumors 2 cm from the dentate line had sphincter-saving surgery.

Conclusion: Preoperative XELOX-RT is a feasible and well tolerated treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based therapy with XELOX chemoradiotherapy.

Supported in part by a grant from Hoffmann-La Roche AG, Grenzach-Wyhlen, Germany, and Sanofi-Synthelabo GmbH, Berlin, Germany.

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