title: Is first-line single-agent mitoxantrone in the treatment of high-risk metastatic breast cancer patients as effective as combination chemotherapy? No difference in survival but higher quality of life were found in a multicenter randomized trial.
abstract: BACKGROUND
  To determine whether patients with high-risk metastatic breast cancer draw benefit from combination chemotherapy as first-line treatment.
  
  
  METHODS
  A total of 260 women with measurable metastatic breast cancer fulfilling high-risk criteria, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either mitoxantrone 12 mg/m(2) or the combination of fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) every 3 weeks. Treatment was continued until complete remission plus two cycles, or until disease progression. In the case of partial remission or stable disease, treatment was stopped after 12 cycles. Second-line treatment was vindesine, mitomycin and prednisolone. Gain from treatment was estimated using a modified Brunner's score composed of time to progression, patients' rating of the treatment benefit, alopecia, vomiting and performance status.
  
  
  RESULTS
  After recruitment from 1992 to 1997 and observation from 1997 to 1999, the final evaluation showed that single-agent treatment with mitoxantrone does not differ significantly from combination treatment with FEC in terms of response, objective remission rate, remission duration, time to response, time to best response, time to progression or overall survival. There was, however, a significant difference in gain from treatment using a modified Brunner's score favoring the single-agent treatment arm. There was no evidence that any subgroup would fare better with combination treatment.
  
  
  CONCLUSIONS
  No significant difference was detected between the treatment with mitoxantrone as a single agent and the combination of low-dose FEC in terms of response or survival; therefore, the imperative of the necessity of first-line combination chemotherapy for patients with high-risk metastatic breast cancer may be questioned. Since toxicity and quality of life score favored the single-agent mitoxantrone treatment arm, this treatment may be offered to patients preferring quality of life to a potential small prolongation of survival.
authors.affiliation: Department of Hematology and Medical Oncology, Deaconess Hospital, Oncological Center of Stuttgart, Germany. heidemann@diak-stuttgart.de
authors.forename: E
authors.initials: E
authors.lastname: Heidemann
authors.forename: H
authors.initials: H
authors.lastname: Stoeger
authors.forename: R
authors.initials: R
authors.lastname: Souchon
authors.forename: W-D
authors.initials: WD
authors.lastname: Hirschmann
authors.forename: H
authors.initials: H
authors.lastname: Bodenstein
authors.forename: C
authors.initials: C
authors.lastname: Oberhoff
authors.forename: J T
authors.initials: JT
authors.lastname: Fischer
authors.forename: M
authors.initials: M
authors.lastname: Schulze
authors.forename: M
authors.initials: M
authors.lastname: Clemens
authors.forename: R
authors.initials: R
authors.lastname: Andreesen
authors.forename: M
authors.initials: M
authors.lastname: Mahlke
authors.forename: M
authors.initials: M
authors.lastname: König
authors.forename: A
authors.initials: A
authors.lastname: Scharl
authors.forename: K
authors.initials: K
authors.lastname: Fehnle
authors.forename: M
authors.initials: M
authors.lastname: Kaufmann
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001707:Biopsy, Needle; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005858:Germany; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary*; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage*; D009367:Neoplasm Staging; D011336:Probability; D016016:Proportional Hazards Models; D011788:Quality of Life; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D015251:Epirubicin; D003520:Cyclophosphamide; D008942:Mitoxantrone; D005472:Fluorouracil