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 M0. 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.

[The German Guideline Clearinghouse on Breast Cancer: the need for frequent updating of breast cancer guidelines requires effective guideline updating procedures]. / Leitlinien-Clearingverfahren Mammakarzinom: Die Notwendigkeit einer häufigen Aktualisierung von Mammakarzinom-Leitlinien erfordert effektive Vorgehensweisen bei der Fortschreibung von Leitlinien.

In order to promote the quality of health care and guidelines in Germany the German Guideline Clearinghouse (Sponsors: German Medical Association, National Association of the Statutory Health Insurance Physicians, German Hospital Federation, Associations of the Sickness Funds and the Statutory Pension Insurance) was established at the Agency for Quality in Medicine (AQuMed) in 1999. The results of the 10th Guideline Clearing Project, the Guideline Clearing Report "Breast Cancer", were published in December 2003. In a systematic search using English/German language guideline databases and literature databases (Medline, Healthstar, Embase), 16 national guidelines were identified which were in accordance to the inclusion criteria (breast cancer treatment; German or English language; published after 1992; new guideline or genuine update (no adaptation); recommended for country-wide implementation). The methodological quality of these 16 guidelines was evaluated using the appraisal instrument of the German Guideline Clearinghouse, the checklist "Methodological Quality of Clinical Practice Guidelines". A peer review of the guidelines was performed by a multidisciplinary focus group of experts (intended guideline users from clinical and ambulatory settings as well as patients). This group consented comments and recommendations for actions of health care policy makers in Germany for a German breast cancer guideline based on examples from the appraised guidelines. None of the identified guidelines contained information about all of the 24 key topics that the focus group considered to be relevant for a German national guideline. The selected exemplary text extracts from the evaluated guidelines can be used as benchmarks and example sources for the development of a national German breast cancer guideline. From the beginning, patients should be involved in the development process within a multidisciplinary team. Due to the rapid emergence of new evidence, oncology guidelines need an effective procedure for updating in order to ensure that they are able to promote health care quality by giving current recommendations based on best available evidence. International networks such as the Guidelines International Network (G-I-N) will be helpful to collect and appraise the evidence for the national guideline development groups in an effective way.