Doxorubicin/pemetrexed followed by docetaxel versus doxorubicin/cyclophosphamide followed by docetaxel as neoadjuvant treatment for early-stage breast cancer:: A randomized phase II trial

Background: Microarray gene expression profiling has indicated that complex molecular gene expression signatures might be predictive of outcome after systemic treatment for early breast cancer. Neoadjuvant systemic therapy (NST) with its assessment of pathologic complete response (pCR), so far the best surrogate parameter for cure, provides a unique opportunity to rapidly identify such molecular predictors. Patients and Methods: Currently, an International, randomized phase II study of 2 sequential regimens as NST is being conducted in patients with primary invasive breast cancer T2-4a-c N0-2 MO. Patients receive 4 cycles of doxorubicin/pemetrexed, followed by 4 cycles of docetaxel (AP-Doc) or 4 cycles of doxorubicin/cyclophosphamide, followed by 4 cycles of docetaxel (AC-Doc). Tumor, tissue, blood, and serum are collected at baseline and, if available, after 4 cycles of chemotherapy, and at surgery. The clinical objectives are to assess pCR rate, tumor response, rate of histologically negative axillary lymph nodes, disease-free survival, and safety after NST with AP-Doc or AC-Doc. Translational research objectives include the identification of differentially expressed genes predictive for the achievement of pCR after either treatment regimen. Results: As of January 2007, 178 of the 256 patients planned for this study had been enrolled at 12 European centers. The recommendation after a planned interim safety and efficacy analysis was to continue with the trial as planned. Conclusion: We anticipate this study will provide a better understanding of the treatment options with pemetrexed in primary breast cancer and give insight into the practical robustness of the new marker sets in response prediction.