title: High-dose mitoxantrone and cyclophosphamide without stem cell support in patients with high-risk and advanced breast carcinoma: a Phase II multicentric trial.
abstract: BACKGROUND
  Currently employed high-dose regimens for patients with breast carcinoma consist mainly of single-cycle combinations of alkylating agents. In a previous Phase I trial, the authors developed a tandem high-dose combination of two cycles of mitoxantrone and cyclophosphamide for the treatment of patients with metastatic breast carcinoma (MBC) and high-risk breast carcinoma (HRBC). Treatment was delivered with granulocyte-colony stimulating factor (G-CSF) but without stem cell support to avoid potential tumor cell reinfusion. The objective was to validate the safety and obtain preliminary efficacy assessment of this combination in a Phase II trial.
  
  
  METHODS
  Fifty-three patients were included: 27 patients with MBC and 26 patients with HRBC. After standard induction treatment, patients received two cycles of mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2 separated by a 4-week interval. Patients received G-CSF and ciprofloxacin until hematologic recovery. Follow-up was performed in an outpatient setting.
  
  
  RESULTS
  One hundred one of 106 projected cycles (95%) were delivered. The mean dose intensities achieved were mitoxantrone 5.8 mg/m2 per week and cyclophosphamide 933 mg/m2 per week. Infection developed in 46% of the cycles, and platelet transfusions were required in 42%. Nonhematologic toxicity was mainly Grade 3 emesis. There were no toxic deaths. In 17 evaluable patients with MBC, 13 patients (77%) had response improvements, including 7 complete responses (41%).
  
  
  CONCLUSIONS
  Treatment with two cycles of mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2 with G-CSF but without stem cell support was well tolerated. The dose intensities achieved approach those obtained with conventional high-dose therapy. This combination warrants further investigation as an alternative to conventional high-dose regimens.
authors.affiliation: Medical Oncology Division, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Pérez-Gracia
authors.forename: R
authors.initials: R
authors.lastname: Colomer
authors.forename: E
authors.initials: E
authors.lastname: Esteban
authors.forename: R
authors.initials: R
authors.lastname: Barceló
authors.forename: M
authors.initials: M
authors.lastname: Benavides
authors.forename: J
authors.initials: J
authors.lastname: Puertas
authors.forename: A
authors.initials: A
authors.lastname: Arcediano
authors.forename: M V
authors.initials: MV
authors.lastname: Tornamira
authors.forename: V
authors.initials: V
authors.lastname: Valentín
authors.forename: A
authors.initials: A
authors.lastname: Muñoz
authors.forename: H
authors.initials: H
authors.lastname: Cortés-Funes
authors.forename: J
authors.initials: J
authors.lastname: Hornedo
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007239:Infections / Q000139:chemically induced; D007262:Infusions, Intravenous; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D012307:Risk Factors; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D008942:Mitoxantrone