title: Prospective, randomized trial of 5-fluorouracil, leucovorin, doxorubicin, and cyclophosphamide chemotherapy in combination with the interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion protein (PIXY321) versus GM-CSF in patients with advanced breast cancer.
abstract: We conducted a prospective randomized trial to evaluate the ability of the interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion protein, PIXY321, to ameliorate cumulative thrombocytopenia after multiple cycles of 5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide (FLAC) chemotherapy compared with GM-CSF in patients with advanced breast cancer. Fifty-three patients were randomized to receive either PIXY321. 375 microg/m2 twice a day subcutaneously, or GM-CSF, 250 microg/m2 daily subcutaneously after FLAC chemotherapy. PIXY321 was less well tolerated than GM-CSF, with more patients developing chills and local skin reactions and more patients stopping PIXY321 due to intolerance. While no difference in the neutrophil nadirs was seen with the two cytokines, the duration of the absolute neutrophil count less than 1,000/muL for all cycles was significantly longer with PIXY321 than with GM-CSF. Fifty percent of patients treated with multiple cycles of FLAC chemotherapy on both study arms developed dose-limiting thrombocytopenia. No differences in platelet nadirs, duration of thrombocytopenia, or need for platelet transfusions were observed with PIXY321 versus GM-CSF. The average delivered doses of FLAC chemotherapy were somewhat higher in the GM-CSF study arm. PIXY321 was not superior to GM-CSF in ameliorating the cumulative thrombocytopenia observed with multiple cycles of FLAC chemotherapy and was less well tolerated.
authors.affiliation: Medicine Branch, Biostatistics and Data Management Section, National Cancer Institute and Clinical Center, National Institutes of Health, Bethesda, MD USA.
authors.forename: J A
authors.initials: JA
authors.lastname: O'Shaughnessy
authors.forename: A
authors.initials: A
authors.lastname: Tolcher
authors.forename: D
authors.initials: D
authors.lastname: Riseberg
authors.forename: D
authors.initials: D
authors.lastname: Venzon
authors.forename: J
authors.initials: J
authors.lastname: Zujewski
authors.forename: M
authors.initials: M
authors.lastname: Noone
authors.forename: M
authors.initials: M
authors.lastname: Gossard
authors.forename: D
authors.initials: D
authors.lastname: Danforth
authors.forename: J
authors.initials: J
authors.lastname: Jacobson
authors.forename: V
authors.initials: V
authors.lastname: Chang
authors.forename: B
authors.initials: B
authors.lastname: Goldspiel
authors.forename: P
authors.initials: P
authors.lastname: Keegan
authors.forename: R
authors.initials: R
authors.lastname: Giusti
authors.forename: K H
authors.initials: KH
authors.lastname: Cowan
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000628:therapy*; D017713:Platelet Transfusion; D011446:Prospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D004317:Doxorubicin; D003520:Cyclophosphamide; D002955:Leucovorin; D005472:Fluorouracil