title: Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study.
abstract: BACKGROUND
  Patients with an early response to neoadjuvant chemotherapy have chemosensitive tumors and a high probability for a pathological complete response at surgery. The relationship between extended chemotherapy and pathological complete response at surgery was investigated in a clinical trial.
  
  
  METHODS
  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) (TAC). Those whose tumor size decreased by 50% or more by sonographic measurement (ie, reduction in the product of the two largest perpendicular diameters by at least 50%) were classified as responders and randomly assigned to receive four or six more cycles of TAC, for a total of six or eight TAC cycles. The primary aim was to increase the rate of a pathological complete response (defined as no invasive or in situ residual tumor masses in the breast and lymph nodes) from 20% to 26%. Sonographic response rates and rates of breast-conserving surgery and adverse effects were also assessed. All statistical tests were two-sided.
  
  
  RESULTS
  Of the 2090 patients in the GeparTrio trial, 1390 (66.5%) were randomly assigned as responders after two initial TAC cycles to receive an additional four (n = 704) or six (n = 686) TAC cycles. Rates of pathological complete response were not statistically significantly different between the arms (21.0% with six TAC cycles and 23.5% with eight TAC cycles; difference = 2.5%, 95% confidence interval [CI] = -1.8% to 6.8%; P = .27). More clinical (48.2% vs 52.9%, difference = 4.7%; 95% CI = -0.55% to 9.95%; P = .08) and sonographic (22.6% vs 27.6%, difference = 5%; 95% CI = 0.45% to 9.55%; P = .033) complete responses at surgery were observed with eight TAC cycles than with six TAC cycles. The rate of breast-conserving surgery was similar in both arms (67.5% vs 68.5%, respectively, P = .68). Grade 3 or 4 leukopenia and edema and various grade 1 or 2 adverse events were more frequent in patients receiving eight TAC cycles than in those receiving six cycles.
  
  
  CONCLUSIONS
  Patients receiving eight TAC cycles had statistically significantly higher sonographic response rates but not pathological complete response rates than those receiving six TAC cycles. However, they also had more toxic effects. So far, eight cycles of TAC cannot be recommended for the whole group of patients responding to two initial cycles of 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; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D016001:Confidence Intervals; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005858:Germany; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D016017:Odds Ratio; D010349:Patient Compliance; D011446:Prospective Studies; D012107:Research Design; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D016217:Ultrasonography, Mammary
chemical_list: D043823:Taxoids; D004317:Doxorubicin; D003520:Cyclophosphamide