Adjuvant treatment of high-risk breast cancer using multicycle high-dose chemotherapy and filgrastim-mobilized peripheral blood progenitor cells

Basser, RL; To, LB; Begley, CG; Juttner, CA; Maher, DW; Szer, J; Cebon, J; Collins, JP; Russell, I; Olver, I; Gill, PG; Fox, RM; Sheridan, WP; Green, MD

Author(s): Basser, RL; To, LB; Begley, CG; Juttner, CA; Maher, DW; Szer, J; Cebon, J; Collins, JP; Russell, I; Olver, I; Gill, PG; Fox, RM; Sheridan, WP; Green, MD;
Details: Publication Year 1995-07,Volume 1,Issue #7,Page 715-721
Journal Title: CLINICAL CANCER RESEARCH
Publication Type: Journal Article
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 mu g/kg daily for 6 days) prior to chemotherapy to mobilize progenitor cells. Patients were then given three cycles of epirubicin (200 mg/m(2)) and cyclophosphamide (4 g/m(2)) at planned 28-day intervals, each followed by infusion of one third of the PBPC collected and daily administration of filgrastim (5 mu g/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.
Publisher: AMER ASSOC CANCER RESEARCH
Keywords: COLONY-STIMULATING FACTOR; AUTOLOGOUS BONE-MARROW; G-CSF; RANDOMIZED TRIAL; TRANSPLANTATION; DOXORUBICIN; TOXICITY; CYCLOPHOSPHAMIDE; EPIRUBICIN; RECOVERY
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Creation Date: 1995-07-01 12:00:00