title: Effect of adjuvant chemotherapy with or without anthracyclines on the activity and efficacy of first-line cyclophosphamide, epidoxorubicin, and fluorouracil in patients with metastatic breast cancer.
abstract: OBJECTIVE
  To evaluate the effect of previous adjuvant chemotherapy with or without anthracyclines on overall survival (OS), progression-free survival (PFS), and objective response (OR) rates of metastatic breast cancer patients treated with cyclophosphamide, epidoxorubicin, and fluorouracil (CEF) as first-line chemotherapy.
  
  
  METHODS
  Three-hundred twenty-six assessable metastatic breast cancer patients entered onto four consecutive randomized trials performed in our Institution and North-West Oncology Group (GONO) cooperative centers from 1983 to 1994. Patients received CEF-based chemotherapy as first-line therapy and were then evaluated. One hundred forty-four patients (44%) did not receive previous adjuvant chemotherapy, and 143 (44%) and 39 (12%) patients received cyclophosphamide, methotrexate, and fluorouracil (CMF)-based and anthracycline-based adjuvant chemotherapy, respectively.
  
  
  RESULTS
  ORs to CEF chemotherapy were observed in 161 patients (49.4%). On univariate analysis, patients who had received prior adjuvant chemotherapy had a significantly lower probability of response than patients who did not: 43% versus 58% (P=.02). No difference between CMF-based (OR rate, 43%) and anthracycline-based (OR rate, 44%) adjuvant chemotherapy was observed. Stepwise logistic regression analysis indicated that adjuvant chemotherapy (P=.005), bone as dominant metastatic site (P=.02), and previous hormonotherapy for metastatic disease (P=.005) were the most important factors in predicting a poor OR rate. The median PFS and OS times of the whole group were 9.8 and 17.9 months, respectively. Patients who did not receive adjuvant chemotherapy had a longer survival time (21.1 months) compared with patients previously treated with CMF-based (15.3 months) or anthracycline-based (15.8 months) adjuvant chemotherapy. Multivariate analysis confirmed adjuvant chemotherapy to be among the strongest prognostic factors associated with both a poor PFS and OS.
  
  
  CONCLUSIONS
  Previous adjuvant chemotherapy adversely affects OR, PFS, and OS in metastatic breast cancer patients treated with the CEF regimen as first-line chemotherapy. No difference was observed between patients previously treated with CMF-based or anthracycline-based adjuvant chemotherapy.
authors.affiliation: Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Venturini
authors.forename: P
authors.initials: P
authors.lastname: Bruzzi
authors.forename: L
authors.initials: L
authors.lastname: Del Mastro
authors.forename: O
authors.initials: O
authors.lastname: Garrone
authors.forename: G
authors.initials: G
authors.lastname: Bertelli
authors.forename: M
authors.initials: M
authors.lastname: Guelfi
authors.forename: S
authors.initials: S
authors.lastname: Pastorino
authors.forename: R
authors.initials: R
authors.lastname: Rosso
authors.forename: M R
authors.initials: MR
authors.lastname: Sertoli
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004054:Diethylstilbestrol / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008593:Menopause; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged
chemical_list: D015251:Epirubicin; D004054:Diethylstilbestrol; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate