title: Randomized, double-blind, placebo-controlled trial to evaluate the hematopoietic growth factor PIXY321 after moderate-dose fluorouracil, doxorubicin, and cyclophosphamide in stage II and III breast cancer.
abstract: OBJECTIVE
  To measure the effect of PIXY321 (granulocyte-macrophage colony-stimulating factor/interleukin-3 S. cerevisiae fusion protein) on the incidence, duration, and complications of neutropenia and thrombocytopenia after moderate-dose fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 750 mg/m(2) (FAC) chemotherapy in patients with stage II and III breast cancer.
  
  
  METHODS
  In this multicenter, randomized, double-blind placebo-controlled trial, 71 women were to receive four 21-day cycles of treatment with moderate-dose FAC chemotherapy by short intravenous infusion on day 1, followed by either placebo or PIXY321 (375 microg/m(2) subcutaneously twice a day) on days 3 to 15. All patients were to receive prophylactic oral ciprofloxacin when the absolute neutrophil count was less than 1,000/microL.
  
  
  RESULTS
  PIXY321 significantly reduced the incidence and duration of grade 3 and grade 4 neutropenia in cycles 1 and 2 and the duration of grade 3 neutropenia in cycles 1 through 4. In cycles 3 and 4, grade 3 thrombocytopenia was significantly more common with PIXY321 (P <.05). Two patients, both in the PIXY321 group, required platelet transfusions. Fever and hospitalization for intravenous antibiotics were significantly more common in the PIXY321 group during cycle 1 only. More patients in the PIXY321 group achieved hematologic recovery by day 22 in cycles 1 through 3, and time to recovery was significantly shorter with PIXY321 in all cycles. FAC dose intensity was roughly 2% higher in the PIXY321 group (P = NS). Nonhematologic events of any intensity occurring with significantly greater overall frequency in the PIXY321 group included injection-site reactions, fever, chills, abdominal pain, and arthralgia. No patient died on study or within 30 days of her last dose of study drug.
  
  
  CONCLUSIONS
  PIXY321 decreased the incidence and duration of FAC-induced grade 3 and 4 neutropenia in cycles 1 and 2 and significantly shortened the time to hematologic recovery in all cycles. However, it produced more systemic toxicity as well as thrombocytopenia in cycles 3 and 4.
authors.affiliation: Texas Oncology, PA, Physician Reliance Network, and Sammons Cancer Center of Baylor University Medical Center, Dallas, TX 75246, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Jones
authors.forename: P
authors.initials: P
authors.lastname: Khandelwal
authors.forename: K
authors.initials: K
authors.lastname: McIntyre
authors.forename: R
authors.initials: R
authors.lastname: Mennel
authors.forename: D
authors.initials: D
authors.lastname: Orr
authors.forename: R
authors.initials: R
authors.lastname: Kirby
authors.forename: E
authors.initials: E
authors.lastname: Agura
authors.forename: L
authors.initials: L
authors.lastname: Duncan
authors.forename: W
authors.initials: W
authors.lastname: Hyman
authors.forename: T
authors.initials: T
authors.lastname: Roque
authors.forename: D
authors.initials: D
authors.lastname: Regan
authors.forename: M
authors.initials: M
authors.lastname: Schuster
authors.forename: N
authors.initials: N
authors.lastname: Dimitrov
authors.forename: L
authors.initials: L
authors.lastname: Garrison
authors.forename: M
authors.initials: M
authors.lastname: Lange
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007377:Interleukin-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced*
chemical_list: D007377:Interleukin-3; C078524:PIXY321 fusion protein, recombinant; D011993:Recombinant Fusion Proteins; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D005472:Fluorouracil