A Study to Compare ETC vs. EC-TX and Ibandronate vs. Observation in Patients With Node-positive Primary Breast Cancer (GAIN)

In the recent AGO-study, a dose-dense and dose-intensified sequence of Epirubicin - Paclitaxel - Cyclophosphamide has shown superior efficacy compared to a conventionally dosed sequence of Epirubicin / Cyclophosphamid and Paclitaxel and was therefore chosen as standard treatment in this study. The experimental arm of EC-TX combines several strategies: the combination of EC will be administered every 2 weeks as a dose-dense regimen, the combination of TX can also be considered as dose-dense due to the weekly application of paclitaxel. Furthermore there is clinical evidence, that a combination of capecitabine and Paclitaxel provide synergistic effects with improved tumour response. A randomized phase III study could demonstrate a survival benefit of a combination of capecitabine with Docetaxel in patients with metastatic breast cancer. This synergistic effect is probably based on the preclinical observed taxane-mediated up-regulation of thymidine phosphorylase in the tumour cell, which give drive to an increased transformation of capecitabine to its active form 5-Fluorouracil. Apart from this synergy, the EC-TX regimen includes now 4 highly active compounds for the treatment of breast cancer. The total doses of Epirubicin and Paclitaxel are identical in both arms. The dosage of Cyclophosphamide is lower in the experimental arm, which is preferred due to the induction of leukaemia at higher doses of Cyclophosphamide. The duration of both arms with 18 and 20 weeks is nearly similar. The 2 by 2 factorial design of the trial provides the additional possibility to explore the efficacy of a bisphosphonate as another strategy to further improve the prognosis of node positive breast cancer.