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Type: Journal article
Title: Adjuvant treatment of high-risk breast cancer using multicycle high-dose chemotherapy and filgrastim-mobilized peripheral blood progenitor cells
Author: Basser, R.
To, L.
Begley, C.
Juttner, C.
Maher, D.
Szer, J.
Cebon, J.
Collins, J.
Russell, I.
Olver, I.
Gill, P.
Fox, R.
Sheridan, W.
Green, M.
Citation: Clinical Cancer Research, 1995; 1(7):715-721
Publisher: American Association for Cancer Research
Issue Date: 1995
ISSN: 1078-0432
Statement of
R L Basser, L B To, C G Begley, C A Juttner, D W Maher, J Szer, J Cebon, J P Collins, I Russell and I Olve
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.
Keywords: Humans
Breast Neoplasms
Lymphatic Metastasis
Granulocyte Colony-Stimulating Factor
Recombinant Proteins
Antineoplastic Combined Chemotherapy Protocols
Neoplasm Staging
Leukocyte Count
Platelet Count
Chemotherapy, Adjuvant
Hematopoietic Stem Cell Transplantation
Middle Aged
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