Influence of sequencing of chemotherapy and radiotherapy regarding adverse effects of the cytostatic treatment: Results of the ADEBAR trial

Abstract

559 Background: The ADEBAR-trial was designed as a multicenter randomised phase III study for high risk primary breast cancer (BC) pts., i.e. with more than 3 axillary lymph node metastases. Primary objective of the trial was to evaluate the benefit of a sequential anthracycline-docetaxel regimen (E90C-D: 4 cycles epirubicin [E] 90 mg/m2 plus cyclophosphamide [C] 600 mg/m2 q21 days followed by 4 cycles docetaxel [D] 100mg/m2 q21 days) compared to dose-intensive anthracycline- containing polychemotherapy (FE120C: 6 cycles E 60 mg/m2 d 1+8, 5-FU 500mg/m2 d 1+8 and C 75 mg/m2 d 1–14, q4 weeks). Patients and Methods: The study started in 2001 and was closed in 2005. By this time 200 actively participating sites had recruited a total number of 1,502 patients. One of the stratification issues was the sequencing of chemotherapy and radiotherapy. All patients were required to receive adjuvant radiotherapy. However the timing of irradiation, either in a sandwich setting after the first half of chemotherapy cycles or after completion of the entire cytostatic treatment was at the discretion of the study sites. In a toxicity-analysis in December 2006, the influence of sequencing of chemotherapy and radiotherapy was analyzed in 980 patients. Results: In 223 pts. radiotherapy was performed midtime after the first half of chemotherapy cycles, 757 pts. received radiotherapy only after completing the entire cytostatic treatment and before starting endocrine treatment, if applicable. Hospitalisation occurred in 32.7 % (73 pts.) of the sandwich group and in 27.9% (211 pts.) of the sequential group (p-value = 0.160). Interval prolongation was necessary in 37.7% (84 pts.) versus 31.6% (239 pts.) in the sequential group, (p-value = 0.089). The target dose was reduced in 15.7% (35 pts.) in the sandwich group and in 20.2% (153 pts.) of the sequential group, (p-value = 0.132). SAEs occurred in 29.6% (66 pts.) in the sandwich group versus 23.1% (175 pts.), (p-value = 0.048). Conclusion: No consistent association between treatment toxicity and the timing of chemotherapy and radiotherapy was observed. Because in this high risk patient group, the prevention of systemic relapse is most important, chemotherapy should be completed before the start of radiotherapy. No significant financial relationships to disclose.