title: Toxicity Assessment of a Phase III Study Evaluating FEC-Doc and FEC-Doc Combined with Gemcitabine as an Adjuvant Treatment for High-Risk Early Breast Cancer: the SUCCESS-A Trial.
abstract: Introduction:This paper aims to evaluate the toxicity profile of additive gemcitabine to adjuvant taxane-based chemotherapy in breast cancer patients.Methods:Patients enrolled in this open-label randomized controlled Phase III study were treated with 3 cycles of epirubicin-fluorouracil-cyclophosphamide (FEC) chemotherapy followed by 3 cycles of docetaxel with those receiving 3 cycles of FEC followed by 3 cycles of gemcitabine-docetaxel (FEC-DG). 3690 patients were evaluated according to National Cancer Institute (NCI) toxicity criteria (CTCAE). The study medications were assessed by the occurrence of grade 3-4 adverse events, dose reductions, postponements of treatment cycles and granulocyte colony-stimulating factor (G-CSF) support.Results:No differences in neutropenia or febrile neutropenia were demonstrated. However, thrombocytopenia was significantly increased with FEC-DG treatment (2.0 vs. 0.5 %, p < 0.001), as was leukopenia (64.1 vs. 58.5 %, p < 0.001). With FEC-DG significantly more G-CSF support in cycles 4 to 6 (FEC-DG: 57.8 %, FEC-D: 36.3 %, p < 0.001) was provided. Transaminase elevation was significantly more common with FEC-DG (SGPT: 6.3 %, SGOT: 2 %), whereas neuropathy (1.2 %), arthralgia (1.6 %) and bone pain (2.6 %) were more common using FEC-D. Dose reductions > 20 % (4 vs. 2.4 %) and postponement of treatment cycles (0.9 vs. 0.4 %) were significantly more frequent in the FEC-DG arm. Eight deaths occurred during treatment in the FEC-DG arm and four in the FEC-D arm.Conclusion:The addition of gemcitabine increased hematological toxicity and was associated with more dose reductions and postponements of treatment cycles.
authors.affiliation: Department of Gynecology and Obstetrics, Ludwig-Maximilians-University, Munich.
authors.forename: L
authors.initials: L
authors.lastname: Schröder
authors.affiliation: Department of Gynecology and Obstetrics, Ludwig-Maximilians-University, Munich.
authors.forename: B
authors.initials: B
authors.lastname: Rack
authors.affiliation: Department of Gynecology and Obstetrics, Ludwig-Maximilians-University, Munich.
authors.forename: H
authors.initials: H
authors.lastname: Sommer
authors.affiliation: Department of Gynecology and Obstetrics, Ludwig-Maximilians-University, Munich.
authors.forename: J G
authors.initials: JG
authors.lastname: Koch
authors.affiliation: Department of Gynecology and Obstetrics, Ludwig-Maximilians-University, Munich.
authors.forename: T
authors.initials: T
authors.lastname: Weissenbacher
authors.affiliation: Department of Gynecology and Obstetrics, University of Ulm, Ulm.
authors.forename: W
authors.initials: W
authors.lastname: Janni
authors.affiliation: Head of Division Gynecologic Oncology National Center for Tumor Diseases, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg.
authors.forename: A
authors.initials: A
authors.lastname: Schneeweiss
authors.affiliation: Luisenkrankenhaus Düsseldorf, Düsseldorf.
authors.forename: M
authors.initials: M
authors.lastname: Rezai
authors.affiliation: Gemeinschaftspraxis Dr. R. Lorenz/N. Hecker, Braunschweig.
authors.forename: R
authors.initials: R
authors.lastname: Lorenz
authors.affiliation: Department of Gynecology and Obstetrics, Heinrich Heine University of Düsseldorf, Düsseldorf.
authors.forename: B
authors.initials: B
authors.lastname: Jäger
authors.affiliation: Department of Gynecology and Obstetrics, University of Ulm, Ulm.
authors.forename: A
authors.initials: A
authors.lastname: Schramm
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen.
authors.forename: L
authors.initials: L
authors.lastname: Häberle
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen.
authors.forename: P A
authors.initials: PA
authors.lastname: Fasching
authors.affiliation: Department of Gynecology and Obstetrics, University of Ulm, Ulm.
authors.forename: T W P
authors.initials: TW
authors.lastname: Friedl
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen.
authors.forename: M W
authors.initials: MW
authors.lastname: Beckmann
authors.affiliation: Department of Gynecology and Obstetrics, University of Ulm, Ulm.
authors.forename: C
authors.initials: C
authors.lastname: Scholz
keywords: adjuvant chemotherapy; breast cancer; gemcitabine; hematological; toxicity