title: Dose-intensive chemotherapy with doxorubicin, cyclophosphamide and GM-CSF fails to improve survival of metastatic breast cancer patients.
abstract: BACKGROUND
  A dose response relationship for doxorubicin and cyclophosphamide has been suggested. In a previous dose finding study we treated advanced breast cancer patients with escalating doses of doxorubicin and cyclophosphamide in combination with GM-CSF. The aim of this study is to further define the acute and cumulative toxicity of this treatment in relation to its antitumor activity.
  
  
  METHODS
  Twenty-eight patients with metastatic breast cancer were treated with doxorubicin (90 mg/m2) and cyclophosphamide (1000 mg/m2) at 3-week intervals. Dose reductions of 10% were applied in the second and fourth cycles. On the second day GM-CSF was started at 250 mu g/m2 daily for 10 days. The intention was to give 6 cycles, but when a complete remission was reached earlier only one more cycle was given as consolidation.
  
  
  RESULTS
  The median number of cycles was 5 (range 2-6). Twenty-three patients responded (82%, 95% CI 69%-97%), with 9 of them achieving a complete response (32%, 95% CI 14%-50%). For the 18 patients evaluable for time to progression and survival the median time to progression was 8 months and the median survival 14.5 months. Toxicity was substantial: grades 3 or 4 neutropenia occurred in 95% of cycles and grades 3-4 thrombocytopenia in 49% of cycles. Grade 3-4 mucositis was present in 13% of the cycles. Weakness and fatigue were always present and were cumulative. Four patients had a decline in the left ventricular ejection fraction (LVEF). These side effects were the reason for discontinuing therapy in 9 of the 28 patients (32%).
  
  
  CONCLUSIONS
  This treatment has a high response rate in comparison with conventional-dose chemotherapy but does not prolong time to progression or survival. The toxicity makes this protocol unsuitable for use as palliative treatment.
authors.affiliation: Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: Honkoop
authors.forename: K
authors.initials: K
authors.lastname: Hoekman
authors.forename: J
authors.initials: J
authors.lastname: Wagstaff
authors.forename: E
authors.initials: E
authors.lastname: Boven
authors.forename: C J
authors.initials: CJ
authors.lastname: van Groeningen
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
authors.forename: J B
authors.initials: JB
authors.lastname: Vermorken
authors.forename: H M
authors.initials: HM
authors.lastname: Pinedo
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis
chemical_list: D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide