title: A novel continuous infusional 5-fluorouracil-based chemotherapy regimen compared with conventional chemotherapy in the neo-adjuvant treatment of early breast cancer: 5 year results of the TOPIC trial.
abstract: BACKGROUND
  To compare the efficacy of continuous infusional 5-fluorouracil (5-FU)-based chemotherapy against conventional bolus chemotherapy in the preoperative treatment of patients with large operable early breast cancer.
  
  
  METHODS
  Four hundred and twenty-six women with histologically proven  3 cm invasive early breast cancer were randomised to receive pre-operative infusional 5-FU 200 mg/m(2) by daily 24 h continuous infusion via a Hickman line for 18 weeks with epirubicin 60 mg/m(2) intravenous (i.v.) bolus on day 1 and cisplatin 60 mg/m(2) i.v. bolus on day 1, both repeating 3-weekly (infusional ECisF), or conventional bolus doxorubicin 60 mg/m(2) i.v. on day 1 and cyclophosphamide 600 mg/m(2) i.v. on day 1, both repeating 3-weekly (AC), both schedules for six courses. Patients subsequently had local therapy (surgery or radiotherapy or both) and tamoxifen 20 mg orally daily as appropriate.
  
  
  RESULTS
  The 5 year results for AC and infusional ECisF, respectively, were as follows: overall response, 75% and 77%; complete clinical remission, 31% and 34%; pathological complete remission (pathCR), 16% for both; and pathCR with residual ductal carcinoma in situ (DCIS), 25% and 24%. Mastectomy rates were 37% and 34%, respectively. Five-year overall survival was 74% for AC and 82% for infusional ECisF (hazard ratio 0.76, 95% confidence interval 0.51-1.13; P = 0.18). Both treatments were well tolerated. Grade III/IV lethargy, vomiting, alopecia and plantar-palmar erythema were significantly greater for infusional ECisF; grade III/IV leucopenia was significantly greater for AC.
  
  
  CONCLUSIONS
  Preoperative continuous infusional 5-FU-based chemotherapy is no more active than conventional AC for early breast cancer; with a median 5 year follow-up, the infusion-based schedule shows a non-significant trend towards improved survival.
authors.affiliation: Royal Marsden Hospital, Fulham Road, Lonson SW3 6JJ, UK. ian.smith@rmh.nthames.nhs.uk
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: A
authors.initials: A
authors.lastname: Howell
authors.forename: S R
authors.initials: SR
authors.lastname: Ebbs
authors.forename: T F
authors.initials: TF
authors.lastname: Hickish
authors.forename: M E R
authors.initials: ME
authors.lastname: O'Brien
authors.forename: J L
authors.initials: JL
authors.lastname: Mansi
authors.forename: C B
authors.initials: CB
authors.lastname: Wilson
authors.forename: A C
authors.initials: AC
authors.lastname: Robinson
authors.forename: P A
authors.initials: PA
authors.lastname: Murray
authors.forename: C G A
authors.initials: CG
authors.lastname: Price
authors.forename: T J
authors.initials: TJ
authors.lastname: Perren
authors.forename: R W
authors.initials: RW
authors.lastname: Laing
authors.forename: J M
authors.initials: JM
authors.lastname: Bliss
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide