title: Adjuvant high-dose therapy with peripheral blood stem cell support for patients with high-risk breast cancer.
abstract: We report on the efficacy and toxicity of a sequential high-dose therapy with peripheral blood stem cell (PBSC) support in 107 patients with high-risk stage II/III breast cancer. There were 90 patients with more than 9 tumour-positive axillary lymph nodes. An induction therapy of two cycles of ifosfamide (total dose, 7,500 mg/m(2)) and epirubicin (120 mg/m(2)) was given, and PBSC were harvested during granulocyte colony-stimulating factor (G-CSF)-supported leukocyte recovery following the second cycle. The PBSC-supported high-dose chemotherapy consisted of two cycles of ifosfamide (total dose 12,000 mg/m(2)), carboplatin (900 mg/m(2)) and epirubicin (180 mg/m(2)). Patients were autografted with a median number of 4.1 x 10(6) CD34+ cells/kg (range 1.9-26.5 x 10(6)), resulting in haematological reconstitution within approximately 2 weeks following high-dose therapy. The toxicity was moderate in general, and there was no treatment-related toxic death. Twenty-nine patients (27.1% of all patients) relapsed between 3 and 46 months following the last cycle of high-dose therapy (median 15 months). The probability of disease-free and overall survival at 3 years was 56% and 83%, respectively. A multivariate analysis showed that patients with stage II disease had a significantly better probability of disease-free survival (71%) in comparison with patients with stage III disease (30%). The probability of disease-free survival was also significantly better for patients with oestrogen receptor-positive tumours (62%) compared with patients with receptor-negative ones (40%). In conclusion, sequential high-dose chemotherapy with PBSC support can be safely administered to patients with high-risk stage II/III breast cancer. Further intensification of the therapy including the addition of non-cross-resistant drugs or immunological approaches may be envisaged for patients with stage III disease and hormone receptor-negative tumours.
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Hospitalstr. 3, D-69115 Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hohaus
authors.forename: S
authors.initials: S
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: M T
authors.initials: MT
authors.lastname: Voso
authors.forename: R F
authors.initials: RF
authors.lastname: Schlenk
authors.forename: D
authors.initials: D
authors.lastname: Wallwiener
authors.forename: G
authors.initials: G
authors.lastname: Bastert
authors.forename: R
authors.initials: R
authors.lastname: Haas
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007937:Leukapheresis; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D016190:Carboplatin; D007069:Ifosfamide