title: Sorafenib in the Treatment of Early Breast Cancer: Results of the Neoadjuvant Phase II Study - SOFIA.
abstract: BACKGROUND
  Sorafenib was tested for neoadjuvant treatment with an anthracycline/taxane-based chemotherapy in the open-label, multicentre, single-arm phase II study, 'SOFIA'.
  
  
  METHODS
  INCLUSION CRITERIA WERE: HER2 negative, cT3, cT4 or cT2 cN+, M0 primary breast cancer. Patients received 4 × epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2) (EC) intravenously (i.v.) in 3-weekly cycles followed or preceded by 12 weeks of paclitaxel (Pw) 80 mg/m(2). In cohort 1, sorafenib started at 800 mg daily with chemotherapy. An initial daily sorafenib dose of 200 mg was escalated, based on individual toxicities, every 3 weeks in cohort 2 (starting with EC) and every 2 weeks in cohort 3 (starting with Pw). The primary objective was to identify the most feasible regimen; secondary objectives were safety, pathological complete response (pCR) at surgery and pharmacokinetics.
  
  
  RESULTS
  Of the 36 recruited patients, 7/12 patients completed the study in cohort 1 and 24/24 patients in cohorts 2 and 3. The median cumulative sorafenib dose per patient was 37%, 65% and 46% in cohorts 1, 2 and 3, respectively. The main grade 3-4 toxicities were neutropenia and hand-foot syndrome. The pCR (ypT0/is) rate was 27.7%. No pharmacokinetic interaction was observed between sorafenib and epirubicin.
  
  
  CONCLUSIONS
  Sorafenib EC-Pw is feasible if the starting dose is 200 mg, escalated every 3 weeks based on the patients' individual toxicities.
authors.affiliation: German Breast Group, Neu-Isenburg, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
authors.affiliation: Department of Pharmacology, University of Cologne, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Rokitta
authors.affiliation: Elisabeth Krankenhaus Kassel, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Conrad
authors.affiliation: Brustzentrum, Frauenklinik, University Munich, Germany.
authors.forename: Nadia
authors.initials: N
authors.lastname: Harbeck
authors.affiliation: Elisabeth Krankenhaus Kassel, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Wüllner
authors.affiliation: Breast Unit, University Hospital Cologne, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Warm
authors.affiliation: Neue Frauenklinik, Luzerner Kantonsspital, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schwedler
authors.affiliation: UFK Rostock, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Gerber
authors.affiliation: Henriettenstiftung Hannover, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Schrader
authors.affiliation: UFK Schleswig-Holstein, Kiel, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Eidtmann
authors.affiliation: German Breast Group, Neu-Isenburg, Germany.
authors.forename: Keyur
authors.initials: K
authors.lastname: Mehta
authors.affiliation: Department of Pharmacology, University of Cologne, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Fuhr
authors.affiliation: German Breast Group, Neu-Isenburg, Germany ; UFK Frankfurt/M., Germany.
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
keywords: Anthracycline; Breast cancer; Pharmacokinetics; Sorafenib; Taxane