title: Adjuvant treatment of high-risk breast cancer using multicycle high-dose chemotherapy and filgrastim-mobilized peripheral blood progenitor cells.
abstract: Women with primary breast cancer associated with extensive axillary node involvement or large primary tumors have a very poor prognosis despite treatment with standard-dose adjuvant chemotherapy. In an attempt to improve the outlook of these patients, we investigated the safety and feasibility of delivering three cycles of high-dose epirubicin and cyclophosphamide supported with filgrastim-mobilized peripheral blood progenitor cells (PBPC). Fifteen previously untreated women, median age 50 (range, 30-58) years, with poor prognosis early stage breast cancer received filgrastim (12 microgram/kg daily for 6 days) prior to chemotherapy to mobilize progenitor cells. Patients were then given three cycles of epirubicin (200 mg/m2) and cyclophosphamide (4 g/m2) at planned 28-day intervals, each followed by infusion of one third of the PBPC collected and daily administration of filgrastim (5 microgram/kg s.c.). Three leukaphereses collected a median of 114.9 (range, 22.7-273.5) x 10(4) granulocyte-macrophage-colony-forming cells/kg body weight. Hemopoietic recovery was rapid after each cycle, and there was no correlation between the rate of recovery and the number of granulocyte-macrophage-colony-forming cells infused. There was a small but significant progressive delay in recovery from hematological and nonhematological toxicities across the three cycles. Left ventricular ejection fraction fell to below 50% in eight (53%) patients, but none developed congestive cardiac failure. Two patients did not complete three cycles because of insufficient PBPC for a third cycle (n = 1) and 2-mercaptoethane sodium sulfonate- related drug reaction during the second cycle (n = 1). There were no deaths during the study or during the follow-up period (median, 70 weeks; range, 50-85 weeks), and no late toxicities occurred. Therefore, we concluded that the delivery of multiple cycles of nonmyeloablative, dose-intensive chemotherapy supported by PBPC and filgrastim is safe, and may be widely applicable to a variety of common chemosensitive cancers with a poor prognosis. The efficacy of three cycles of high-dose epirubicin and cyclophosphamide is to be compared with standard-dose chemotherapy in a randomized trial in patients with high-risk, operable stage II and III breast cancer.
authors.affiliation: Centre for Developmental Therapeutics-affiliates: Melbourne Tumor Biology Branch, Ludwig Institute for Cancer Research, Department of Medical Oncology,Heidelberg, Victoria, Australia.
authors.forename: R L
authors.initials: RL
authors.lastname: Basser
authors.forename: L B
authors.initials: LB
authors.lastname: To
authors.forename: C G
authors.initials: CG
authors.lastname: Begley
authors.forename: C A
authors.initials: CA
authors.lastname: Juttner
authors.forename: D W
authors.initials: DW
authors.lastname: Maher
authors.forename: J
authors.initials: J
authors.lastname: Szer
authors.forename: J
authors.initials: J
authors.lastname: Cebon
authors.forename: J P
authors.initials: JP
authors.lastname: Collins
authors.forename: I
authors.initials: I
authors.lastname: Russell
authors.forename: I
authors.initials: I
authors.lastname: Olver
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007937:Leukapheresis; D007958:Leukocyte Count; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D010976:Platelet Count; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D003520:Cyclophosphamide; D000069585:Filgrastim