title: Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating-factor support for dose-intensive cyclophosphamide, etoposide, and cisplatin.
abstract: This is a double-blind randomized placebo-controlled trial to evaluate the efficacy and safety of granulocyte-macrophage colony-stimulating-factor (GM-CSF) after dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP). Fifty-six patients with lymphoma or breast carcinoma were randomized to receive GM-CSF 250 microg/m2 or placebo subcutaneously (SC) every 12 hr after each course of DICEP until recovery of absolute neutrophil count (ANC) of 1.5 x 10(9)/L. Each patient was to receive three courses of DICEP. There were 28 patients in each group. The median duration of ANC below 0.5 x 10(9)/L was 10 versus 12 days for Course 1 (P = 0.010), 10 versus 12 days for Course 2 (P = 0.248), and 16.5 versus 15 days for Course 3 (P = 0.126); platelet counts below 20 x 10(9)/L was 4 versus 4 days for Course 1 (P = 0.586), 8.5 versus 7 days for Course 2 (P = 0.013), and 23.5 versus 10.5 days for Course 3 (P = 0.104); hospitalization for patients readmitted with cytopenic fever were 4 versus 8 days for Course 1 (P = 0.035); 7 versus 6 days for Course 2 (P = 0.692); and 8 versus 12 days for Course 3 (P = 0.884) in the GM-CSF and placebo group, respectively. GM-CSF significantly shortens the duration of neutropenia and readmission only during the first course of DICEP. There was a delay in platelet recovery and an increase in transfusion requirement during subsequent courses in the GM-CSF group. The result cautions the routine use of lineage specific hematopoietic growth factors in supporting repeated cycles of dose-intensive chemotherapy.
authors.affiliation: University of New Mexico Cancer Center, Albuquerque, New Mexico, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Yau
authors.forename: J A
authors.initials: JA
authors.lastname: Neidhart
authors.forename: P
authors.initials: P
authors.lastname: Triozzi
authors.forename: S
authors.initials: S
authors.lastname: Verma
authors.forename: J
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: D P
authors.initials: DP
authors.lastname: Quick
authors.forename: D G
authors.initials: DG
authors.lastname: Mayernik
authors.forename: D H
authors.initials: DH
authors.lastname: Oette
authors.forename: F A
authors.initials: FA
authors.lastname: Haynes
authors.forename: J
authors.initials: J
authors.lastname: Holcenberg
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000209:etiology / Q000517:prevention & control; D001803:Blood Transfusion; D001943:Breast Neoplasms / Q000188:drug therapy; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007902:Length of Stay; D007958:Leukocyte Count; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control* / Q000628:therapy; D010976:Platelet Count; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D002945:Cisplatin