title: Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial.
abstract: BACKGROUND
  Among breast cancer patients, nonresponse to initial neoadjuvant chemotherapy is associated with unfavorable outcome. We compared the response of nonresponding patients who continued the same treatment with that of patients who switched to a well-tolerated non-cross-resistant regimen.
  
  
  METHODS
  Previously untreated breast cancer patients received two 3-week cycles of docetaxel at 75 mg/m(2), doxorubicin at 50 mg/m(2), and cyclophosphamide at 500 mg/m(2) per day (TAC). Patients whose tumors did not decrease in size by at least 50% were randomly assigned to four additional cycles of TAC or to four cycles of vinorelbine at 25 mg/m(2) and capecitabine at 2000 mg/m(2) (NX). The outcome was sonographic response, defined as a reduction in the product of the two largest perpendicular diameters by at least 50%. A difference of 10% or less in the sonographic response qualified as noninferiority of the NX treatment. Pathological complete response was defined as no invasive or in situ residual tumor masses in the breast and lymph nodes. Toxic effects were assessed. All statistical tests were two-sided.
  
  
  RESULTS
  Of 2090 patients enrolled in the GeparTrio study, 622 (29.8%) who did not respond to two initial cycles of TAC were randomly assigned to an additional four cycles of TAC (n = 321) or to four cycles of NX (n = 301). Sonographic response rate was 50.5% for the TAC arm and 51.2% for the NX arm. The difference of 0.7% (95% confidence interval = -7.1% to 8.5%) demonstrated noninferiority of NX (P = .008). Similar numbers of patients in both arms received breast-conserving surgery (184 [57.3%] in the TAC arm vs 180 [59.8%] in the NX arm) and had a pathological complete response (5.3% vs 6.0%). Fewer patients in the NX arm than in the TAC arm had hematologic toxic effects, mucositis, infections, and nail changes, but more had hand-foot syndrome and sensory neuropathy.
  
  
  CONCLUSIONS
  Pathological complete responses to both regimens were marginal. Among patients who did not respond to the initial neoadjuvant TAC treatment, similar efficacy but better tolerability was observed by switching to NX than continuing with TAC.
authors.affiliation: German Breast Group, Frankfurt, Germany. minckwitz@germanbreastgroup.de
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Sherko
authors.initials: S
authors.lastname: Kümmel
authors.forename: Petra
authors.initials: P
authors.lastname: Vogel
authors.forename: Claus
authors.initials: C
authors.lastname: Hanusch
authors.forename: Holger
authors.initials: H
authors.lastname: Eidtmann
authors.forename: Jörn
authors.initials: J
authors.lastname: Hilfrich
authors.forename: Bernd
authors.initials: B
authors.lastname: Gerber
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.forename: Serban Dan
authors.initials: SD
authors.lastname: Costa
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
authors.forename: Keyur
authors.initials: K
authors.lastname: Mehta
authors.forename: Manfred
authors.initials: M
authors.lastname: Kaufmann
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D000069287:Capecitabine; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy; D018275:Carcinoma, Lobular / Q000188:drug therapy; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005858:Germany; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D010349:Patient Compliance; D011446:Prospective Studies; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D016217:Ultrasonography, Mammary; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D043823:Taxoids; D003841:Deoxycytidine; D014747:Vinblastine; D000069287:Capecitabine; D004317:Doxorubicin; D003520:Cyclophosphamide; D000077235:Vinorelbine; D005472:Fluorouracil