title: Tandem high-dose therapy with ifosfamide, epirubicin, carboplatin and peripheral blood stem cell support is an effective adjuvant treatment for high-risk primary breast cancer.
abstract: We evaluated the therapeutic efficacy and toxicity of a tandem high-dose therapy with peripheral blood stem cell (PBSC) support in 40 patients with high-risk, primary breast cancer (stage II-III) and involvement of ten or more positive axillary lymph nodes. Their median age was 44 years (range 23-56). Two cycles of cytotoxic chemotherapy with ifosfamide (10000 mg/m2) and epirubicin (100 mg/m2) were administered. Granulocyte colony-stimulating factor (G-CSF) was given to hasten neutrophil reconstitution and to mobilise PBSC during marrow recovery. Leukaphereses were performed following the first and/or second cycle. Tandem high-dose therapy consisted of two cycles with ifosfamide (15 or 12 g/m2) and epirubicin (150 mg/m2), while carboplatin (900 mg/m2) was added for the last 24 patients included. Using an immunocytochemical method, two of 11 patients had cytokeratin-positive tumour cells in three leukapheresis products that were collected following the first G-CSF-supported cycle with ifosfamide and epirubicin, whereas only two harvests obtained following the second cycle in 26 patients contained cytokeratin-positive tumour cells. The number of CD34+ cells/kg re-infused following both high-dose cycles was similar (4.20 +/- 0.29 x 10(6), first cycle and 5.25 +/- 0.63 x 10(6), second cycle), and no notable difference was noted in the speed of haematological reconstitution. An absolute neutrophil count (ANC) of 0.5 x 10(9)/1 was reached after a median time of 13 days, while an unsupported platelet count of 20.0 x 10(9)/1 was achieved after a median time of 8 (first cycle) and 9 (second cycle) days post-transplantation. Patients autografted with more than 7.5 x 10(6) CD34+ cells/kg had platelet counts above 20 x 10(9)/1 within less than 10 days. 6 patients relapsed between 7 and 11 months (median 8 months) post-transplantation. 37 patients are alive and in remission with a median follow-up time of 11 months (range 1-38). This translates into a probability of disease-free survival (DFS) of 77% (95% CI 32-95%) at 38 months. The probability of overall survival is 85%, since 3 patients with local relapse achieved a second complete remission following surgery and involved-field radiotherapy. In conclusion, a sequential high-dose therapy including ifosfamide, epirubicin, carboplatin and PBSC support is well tolerated and effective in patients with high-risk primary breast cancer. Involved-field irradiation should be performed post-transplantation to reduce the risk of local relapse.
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Haas
authors.forename: H
authors.initials: H
authors.lastname: Schmid
authors.forename: U
authors.initials: U
authors.lastname: Hahn
authors.forename: S
authors.initials: S
authors.lastname: Hohaus
authors.forename: H
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: S
authors.initials: S
authors.lastname: Murea
authors.forename: M
authors.initials: M
authors.lastname: Kaufmann
authors.forename: M
authors.initials: M
authors.lastname: Wannenmacher
authors.forename: D
authors.initials: D
authors.lastname: Wallwiener
authors.forename: G
authors.initials: G
authors.lastname: Bastert
authors.forename: W
authors.initials: W
authors.lastname: Hunstein
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008875:Middle Aged; D011994:Recombinant Proteins; D015996:Survival Rate
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D016190:Carboplatin; D000069585:Filgrastim; D007069:Ifosfamide