Phase I trial of recombinant human granulocyte-macrophage colony-stimulating factor derived from yeast in patients with breast cancer receiving cyclophosphamide, doxorubicin, and fluorouracil.
OBJECTIVE
To establish the optimum biologic dose and maximal-tolerated dose (MTD) of once-daily, subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor derived from yeast (RhuGM-CSF) in patients with breast cancer.


METHODS
Seventeen patients with either newly diagnosed breast cancer with more than four involved axillary nodes (five patients) or metastatic breast cancer (12 patients) were treated with cyclophosphamide 1 g/m2, doxorubicin 50 mg/m2, and fluorouracil 500 mg/m2 (CAF) intravenously (IV) once every 3 weeks. RhuGM-CSF was administered subcutaneously once daily for 14 days after the second and third CAF cycles, at one of three dose levels.


RESULTS
The 125-micrograms/m2/d RhuGM-CSF dose level shortened the duration of neutropenia in only one of three patients. The 250-micrograms/m2/d level was effective in shortening the duration of the neutropenic nadir (< .5 x 10(9)/dL) by 2 or more days in five of six patients. The 500-micrograms/m2/d level caused severe toxicity (chest pain, two patients; deep vein thrombosis, one patient) in three of eight patients.


CONCLUSIONS
RhuGM-CSF administered once daily at the 250-micrograms/m2/d level is well tolerated and effective in shortening the duration of the neutrophil nadir by 2 or more days after CAF therapy.
O'Reilly
S E
SE
British Columbia Cancer Agency, Vancouver Clinic, University of British Columbia, Canada.
Gelmon
K A
KA
Onetto
N
N
Parente
J
J
Rubinger
M
M
Page
R A
RA
Plenderleith
I H
IH
D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000009:adverse effects; D004317:Doxorubicin / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012441:Saccharomyces cerevisiae
D011994:Recombinant Proteins; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D005472:Fluorouracil