title: Neoadjuvant vinorelbine/epirubicin (VE) versus standard adriamycin/cyclophosphamide (AC) in operable breast cancer: analysis of response and tolerability in a randomised phase III trial (TOPIC 2).
abstract: BACKGROUND
  Vinorelbine is active and well tolerated against advanced breast cancer but there are no published efficacy studies in early breast cancer. We have therefore carried out a randomised phase III neoadjuvant trial in operable breast cancer.
  
  
  METHODS
  Patients with > or =3 cm operable breast carcinoma were randomised to receive either vinorelbine 25 mg/m(2) on days 1 and 8 and epirubicin 60 mg/m(2) on day 1, 3 weekly for six cycles (VE) or doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) i.v. on day 1, 3 weekly for six cycles (AC), prior to standard local therapy, and adjuvant endocrine therapy as appropriate.
  
  
  RESULTS
  A total of 451 patients were randomised. Results for AC and VE, respectively, were: overall clinical response 73% and 74%, complete clinical remission 20% and 24%, pathological complete remission 12% and 12%, mastectomy rate 52% and 55%. None of these differences were significant. Dose reduction was required in 8% for AC and 20% for VE (P <0.001) (GSCF support not used). Significantly more grade 3/4 toxicity for nausea, vomiting and alopecia (despite scalp cooling) was seen for AC compared with VE but significantly less grade 3/4 thrombophlebitis and neuropathy.
  
  
  CONCLUSIONS
  Neoadjuvant VE is as effective as AC in early breast cancer and was better tolerated except for thrombophlebitis and neuropathy.
authors.affiliation: Royal Marsden Hospital, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Chua
authors.forename: I E
authors.initials: IE
authors.lastname: Smith
authors.forename: R P
authors.initials: RP
authors.lastname: A'Hern
authors.forename: G A
authors.initials: GA
authors.lastname: Coombes
authors.forename: T F
authors.initials: TF
authors.lastname: Hickish
authors.forename: A C
authors.initials: AC
authors.lastname: Robinson
authors.forename: R W
authors.initials: RW
authors.lastname: Laing
authors.forename: M E R
authors.initials: ME
authors.lastname: O'Brien
authors.forename: S R
authors.initials: SR
authors.lastname: Ebbs
authors.forename: A
authors.initials: A
authors.lastname: Hong
authors.forename: A
authors.initials: A
authors.lastname: Wardley
authors.forename: T
authors.initials: T
authors.lastname: Mughal
authors.forename: M
authors.initials: M
authors.lastname: Verrill
authors.forename: D
authors.initials: D
authors.lastname: Dubois
authors.forename: J M
authors.initials: JM
authors.lastname: Bliss
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D012074:Remission Induction; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D015251:Epirubicin; D014747:Vinblastine; D004317:Doxorubicin; D003520:Cyclophosphamide; D000077235:Vinorelbine