TY - JOUR
T1 - Neoadjuvant capecitabine combined with standard radiotherapy in patients with locally advanced rectal cancer: Mature results of a phase II trial
AU - Dunst, Juergen
AU - Debus, Juergen
AU - Rudat, Volker
AU - Wulf, Joern
AU - Budach, Wilfried
AU - Hoelscher, Tobias
AU - Reese, Thomas
AU - Mose, Stephan
AU - Roedel, Claus
AU - Zuehlke, Helmut
AU - Hinke, Axel
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2008/9
Y1 - 2008/9
N2 - Purpose: The objective of this expanded phase II trial was to confirm the safety results of the preceding phase I study and establish 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 university 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/m2bid on each day of the radiotherapy period with the first daily dose applied 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-preserving 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 downstaging in 61%. Acute toxicity with > 5% incidence of NCI (National Cancer Institute) grade ≥ 3 included lymphopenia (12%), leukopenia (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 chemoradiation of rectal cancer with a favorable safety profile.
AB - Purpose: The objective of this expanded phase II trial was to confirm the safety results of the preceding phase I study and establish 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 university 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/m2bid on each day of the radiotherapy period with the first daily dose applied 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-preserving 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 downstaging in 61%. Acute toxicity with > 5% incidence of NCI (National Cancer Institute) grade ≥ 3 included lymphopenia (12%), leukopenia (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 chemoradiation of rectal cancer with a favorable safety profile.
UR - http://www.scopus.com/inward/record.url?scp=56549126162&partnerID=8YFLogxK
U2 - 10.1007/s00066-008-1751-4
DO - 10.1007/s00066-008-1751-4
M3 - Journal articles
C2 - 19016023
AN - SCOPUS:56549126162
SN - 0179-7158
VL - 184
SP - 450
EP - 456
JO - Strahlentherapie und Onkologie
JF - Strahlentherapie und Onkologie
IS - 9
ER -