title: Doxorubicin/pemetrexed followed by docetaxel versus doxorubicin/ cyclophosphamide followed by docetaxel as neoadjuvant treatment for early-stage breast cancer: a randomized phase II trial.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gynecology and Obstetrics, University of Heidelberg, Germany. andreas.schneeweiss@med.uni-heidelberg.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: Ilka
authors.initials: I
authors.lastname: Lauschner
authors.forename: Amparo
authors.initials: A
authors.lastname: Ruiz
authors.forename: Angel
authors.initials: A
authors.lastname: Guerrero
authors.forename: Pedro
authors.initials: P
authors.lastname: Sánchez-Rovira
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Seguí
authors.forename: Kay
authors.initials: K
authors.lastname: Goerke
authors.forename: Michael
authors.initials: M
authors.lastname: Wolf
authors.forename: Alexeyg G
authors.initials: AG
authors.lastname: Manikhas
authors.forename: Juergen
authors.initials: J
authors.lastname: Wacker
authors.forename: Frederik
authors.initials: F
authors.lastname: Marmé
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Sinn
authors.forename: Christof
authors.initials: C
authors.lastname: Sohn
authors.forename: Kambiz
authors.initials: K
authors.lastname: Mansouri
authors.forename: Thomas
authors.initials: T
authors.lastname: Bauknecht
authors.forename: Meinhard
authors.initials: M
authors.lastname: Hahn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D000068437:Pemetrexed; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D043823:Taxoids; D000068437:Pemetrexed; D000077143:Docetaxel; D006147:Guanine; D004317:Doxorubicin; D003520:Cyclophosphamide