Sibylle Loibl1, Dennis Rokitta2, Bettina Conrad3, Nadia Harbeck4, Michaela Wüllner3, Mathias Warm5, Kathrin Schwedler6, Bernd Gerber7, Iris Schrader8, Holger Eidtmann9, Keyur Mehta1, Uwe Fuhr2, Gunter von Minckwitz10. 1. German Breast Group, Neu-Isenburg, Germany. 2. Department of Pharmacology, University of Cologne, Germany. 3. Elisabeth Krankenhaus Kassel, Germany. 4. Brustzentrum, Frauenklinik, University Munich, Germany. 5. Breast Unit, University Hospital Cologne, Germany. 6. Neue Frauenklinik, Luzerner Kantonsspital, Germany. 7. UFK Rostock, Germany. 8. Henriettenstiftung Hannover, Germany. 9. UFK Schleswig-Holstein, Kiel, Germany. 10. German Breast Group, Neu-Isenburg, Germany ; UFK Frankfurt/M., Germany.
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'. PATIENTS AND 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. CONCLUSION: Sorafenib EC-Pw is feasible if the starting dose is 200 mg, escalated every 3 weeks based on the patients' individual toxicities.
BACKGROUND:Sorafenib was tested for neoadjuvant treatment with an anthracycline/taxane-based chemotherapy in the open-label, multicentre, single-arm phase II study, 'SOFIA'. PATIENTS AND 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. CONCLUSION:Sorafenib EC-Pw is feasible if the starting dose is 200 mg, escalated every 3 weeks based on the patients' individual toxicities.
Entities:
Keywords:
Anthracycline; Breast cancer; Pharmacokinetics; Sorafenib; Taxane
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