450 Strahlenther Onkol 2008 · No. 9 © Urban & Vogel Strahlentherapie und Onkologie Original Article Neoadjuvant Capecitabine Combined with Standard Radiotherapy in Patients with Locally Advanced Rectal Cancer Mature Results of a Phase II Trial* Juergen Dunst 1 , Juergen Debus 2 , Volker Rudat 3 , Joern Wulf 4 , Wilfried Budach 5 , Tobias Hoelscher 6 , Thomas Reese 7 , Stephan Mose 8 , Claus Roedel 8 , Helmut Zuehlke 9 , Axel Hinke 10 Purpose: The objective of this expanded phase II trial was to confirm the safety results of the preceding phase I study and es- tablish the efficacy of neoadjuvant radiochemotherapy with capecitabine in rectal cancer in a multicenter setting. Patients and Methods: 96 patients (63% male, age 34–81 years) with advanced rectal cancer (cT3–4 or cN+) from seven univer- sity centers in Germany were recruited. All were to receive a total irradiation dose of 50.4–55.8 Gy with conventional fractions. Capecitabine was given at an oral dosage of 825 mg/m 2 bid on each day of the radiotherapy period with the first daily dose ap- plied 2 h before irradiation, followed by surgery 6 weeks later. Results: Most of the patients suffered from an advanced primary tumor (cT3: 57%, cT4: 40%) with lymph node involvement in 60%. After neoadjuvant treatment, with a mean of 99% of the scheduled radiation dose actually delivered, a clinical response rate of 68% (95% confidence interval: 57–78%) was observed. Out of 87 evaluable patients undergoing surgery, a sphincter-pre- serving procedure could be performed in 51% and R0 resection in 94%. A pathologically complete response was achieved in six patients (7%, 95% confidence interval: 3–14%). The comparison of initial diagnosis and pathologic findings showed a downstag- ing in 61%. Acute toxicity with > 5% incidence of NCI (National Cancer Institute) grade ≥ 3 included lymphopenia (12%), leuko- penia (6%), and diarrhea (7%). Mild to moderate hand-foot syndrome occurred in 12% only. After a median follow-up of 48 months, the 5-year overall survival and tumor control data were, with regard to patient selection, in the expected range with an overall survival of 65%, a relapse-free survival of 47%, and a local recurrence rate after 5 years of 17%. Conclusion: The data clearly confirm that capecitabine is an adequate substitute for 5-fluorouracil in preoperative chemoradia- tion of rectal cancer with a favorable safety profile. Key Words: Capecitabine · Rectal cancer · Radiotherapy · Neoadjuvant therapy · Phase II study Strahlenther Onkol 2008;184:450–6 DOI 10.1007/s00066-008-1751-4 Präoperative Radiochemotherapie mit Capecitabin beim lokal fortgeschrittenen Rektumkarzinom: Langzeitergebnisse einer Phase-II-Studie Ziel: Diese multizentrische Phase-II-Studie sollte Effektivität und Toxizität einer neoadjuvanten Radiochemotherapie mit Capeci- tabine prüfen. Patienten und Methodik: 96 Patienten (davon 63% männlich, Alter 34–81 Jahre) mit lokal fortgeschrittenem Rektumkarzinom (cT3–4 oder cN+) aus sieben deutschen Universitätskliniken wurden rekrutiert. Alle erhielten eine präoperative Radiotherapie (50,4–55,8 Gy in konventioneller Fraktionierung mit 5 × 1,8 Gy) und zusätzlich 2 × täglich 825 mg/m 2 Capecitabin während der Received: April 16, 2007; accepted: June 13, 2008 * Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, USA, June 5–8, 2004. 1 Department of Radiotherapy, University of Lübeck, Germany, 2 University of Heidelberg, Germany, 3 University of Hamburg, Germany, 4 University of Würzburg, Germany, 5 University of Tübingen, Germany, 6 Technical University, Dresden, Germany, 7 Martin Luther University, Halle, Germany, 8 University of Frankfurt, Germany, 9 Paul Gerhard Hospital, Wittenberg, Germany, 10 WiSP GmbH, Langenfeld, Germany.