title: Dose-dense primary systemic chemotherapy with gemcitabine plus epirubicin sequentially followed by docetaxel for early breast cancer: final results of a phase I/II trial.
abstract: We recruited 50 patients with T2-4 N0-2 M0 primary breast cancer into a phase I/II study to define the maximum tolerated dose (MTD), efficacy and tolerability of preoperative gemcitabine (1250 mg/m fixed dose) plus epirubicin (doses escalated from 90 mg/m) for 5 cycles followed by 4 cycles of docetaxel (scheduled fixed dose 100 mg/m) given on day 1 every 2 weeks (q2w) with pegfilgrastim support. The MTD for epirubicin was 100 mg/m, but the docetaxel dose had to be reduced to 80 mg/m. Dose-limiting toxicities included fatigue, stomatitis, diarrhea and dyspnea (all grade 3) during gemcitabine plus epirubicin, and fatigue (grade 3) and allergic reaction (grade 4) during docetaxel treatment, respectively. A pathologic complete response could be achieved in 13 patients (pT0+pTis, 26%), and in the breast and axilla in 12 patients [(pT0 or pTis)+pN0, 24%). Breast-conserving surgery (BCS) was possible in 35 patients (70%). Main grade 3/4 adverse events at MTD were fatigue (57/0%), leukopenia (27/8%), and liver (14/0%) and lung toxicity (14/0%). In conclusion, gemcitabine plus epirubicin 1250/100 mg/m q2w followed sequentially by docetaxel 80 mg/m q2w is highly effective as pre-operative chemotherapy with manageable toxicity. However, response and BCS rates could not be increased by administering gemcitabine plus epirubicin and docetaxel in a dose-dense fashion.
authors.affiliation: Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany. andreas_schneeweiss@med.uni-heidelberg.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: Florian
authors.initials: F
authors.lastname: Schuetz
authors.forename: Christian
authors.initials: C
authors.lastname: Rudlowski
authors.forename: Meinhard
authors.initials: M
authors.lastname: Hahn
authors.forename: Ilka
authors.initials: I
authors.lastname: Lauschner
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Sinn
authors.forename: Dietrich
authors.initials: D
authors.lastname: von Fournier
authors.forename: Christof
authors.initials: C
authors.lastname: Sohn
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000188:drug therapy; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D000068256:Darbepoetin alfa; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D004921:Erythropoietin / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D009503:Neutropenia / Q000517:prevention & control; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D011994:Recombinant Proteins; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000068256:Darbepoetin alfa; D003841:Deoxycytidine; D000077143:Docetaxel; D015251:Epirubicin; D004921:Erythropoietin; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor; D019394:Ki-67 Antigen; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011994:Recombinant Proteins; D043823:Taxoids; D000093542:Gemcitabine; C455861:pegfilgrastim