Rapid hematopoietic recovery after multicycle high-dose chemotherapy: enhancement of filgrastim-induced progenitor-cell mobilization by recombinant human stem-cell factor.
OBJECTIVE
To assess the mobilization potential and safety of recombinant human stem-cell factor (SCF) when coadministered with filgrastim to untreated women with poor-prognosis breast cancer.


METHODS
Eligible women had breast cancer with 10 or more positive axillary nodes, or estrogen receptor-negative tumor with 4 positive nodes, or stage III disease. Patients were randomized to receive SCF plus filgrastim or filgrastim alone. Filgrastim 12 microg/kg daily was administered for 6 days by continuous subcutaneous infusion. SCF was administered by daily subcutaneous injection at 5, 10, or 15 microg/kg concurrent with filgrastim for 7 days, or 10 microg/kg daily starting 3 days before filgrastim for a total of 10 days (SCF pretreatment). Apheresis was performed on days 5, 6, and 7 of filgrastim administration. Patients then had three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 g/m2 every 28 days, each supported by one third of the apheresis product.


RESULTS
Sixty-two women were treated. Greater yields occurred in patients who received SCF 10 microg/kg daily plus filgastim than those who received filgrastim alone (P=.013 for CD34+ cells; P=.07 for granulocyte-macrophage colony-forming cells [GM-CFCs]). The difference was more marked with SCF-pretreatment than concurrent SCF. Fewer aphereses were required to reach the predetermined target of peripheral-blood progenitor/stem cells (PBPCs) in women who received SCF. SCF was generally well tolerated. Hematologic recovery was rapid after each of the three cycles of chemotherapy. There was no difference in recovery between the different treatment groups.


CONCLUSIONS
Mobilization of PBPCs by filgrastim is significantly enhanced by coadministration of SCF, and commencing SCF before filgrastim can optimize this effect. SCF has the potential to reduce the number of aphereses required to collect a target number of PBPCs.
Basser
R L
RL
Centre for Developmental Cancer Therapeutics, Royal Melbourne Hospital, Parkville, Victoria, Australia. basser@licre.ludwig.edu
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Begley
C G
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Maher
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Juttner
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Cebon
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Mansfield
R
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Olver
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Duggan
G
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Szer
J
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Collins
J
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Schwartz
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Marty
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Menchaca
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Sheridan
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Fox
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Green
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D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001772:Blood Cell Count; D001781:Blood Component Removal; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D015672:Erythroid Precursor Cells; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006410:Hematopoiesis / Q000187:drug effects; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D016131:Lymphocyte Subsets; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D019089:Stem Cell Factor / Q000008:administration & dosage* / Q000009:adverse effects
D018952:Antigens, CD34; D006454:Hemoglobins; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D003520:Cyclophosphamide; D000069585:Filgrastim