The ADEBAR-trial: The sequencing of regional radiotherapy and chemotherapy does not influence cytostatic dose intensity

Abstract

744 Background: ADEBAR is a multicenter phase III trial to evaluate whether breast cancer (BC) pts with > 3 axillary lymph metastases benefit from 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). We analyzed the influence of timing of regional radiotherapy on the cytostatic dose density. Methods: As of June 1st 2004, 176 actively participating centers recruited 994 patients (29.2 patients/month, median) in the ADEBAR-study. Participating centers opted to time the mandatory regional radiotherapy, including breast or chest wall and infra-/supraclavicular irradiation, within a sandwich setting after half of the chemotherapy cycles, or after completion of the entire cytostatic treatment. Complete treatment data were evaluable of 435 patients. Results: In 336 pts (77.2%), radiotherapy was performed after the completion of all chemotherapy cycles, in 99 pts radiotherapy was performed after completing half of the chemotherapy cycles. At least one serious adverse event occurred in 86 pts (19.8%), and in 2.8% of the chemotherapy cycles. The interval between cycles was prolonged at least once in 142 pts (32.6%) and dose reduction was performed at least once in 75 pts (17.2%). Hospitalisation was necessary at least once in 125 pts (28.7%). The sequencing of radiotherapy and chemotherapy did not correlate with the incidence of serious adverse events (0.65), interval prolongation (p=0.29), and hospitalisation (p=0.71). There was a non-significant trend for more frequent dose reduction in patients with sequential treatment (19.0% vs. 11.1%, p=0.07). Conclusions: The sequencing of regional radiotherapy and chemotherapy - sandwich or sequential - does not influence cytostatic dose density. However, because of the predominant risk for life threatening distant metastasis, we recommend to complete the chemotherapy before starting radiotherapy in patients with more than three axillary lymph node metastases. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Novartis, Pierre Fabre Aventis, Novartis, Pierre Fabre