title: Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin.
abstract: OBJECTIVE
  Thrombocytopenia may compromise cancer treatment, causing chemotherapy dose reductions, schedule alterations, or the need for platelet transfusions. We evaluated the efficacy and safety of recombinant human interleukin-11 (rhIL-11; Neumega, Genetics Institute, Inc, Cambridge, MA), a novel thrombopoietic growth factor, in reducing the need for platelet transfusions in patients who undergo dose-intensive chemotherapy.
  
  
  METHODS
  Women with advanced breast cancer received cyclophosphamide (3,200 mg/m2) and doxorubicin (75 mg/m2) plus granulocyte colony-stimulating factor (G-CSF; 5 microg/kg/d). Patients were randomized to blinded treatment with placebo or 50 microg/kg/d rhIL-11 subcutaneously for 10 or 17 days after the first two chemotherapy cycles.
  
  
  RESULTS
  Seventy-seven patients were randomized and constitute the intent-to-treat (ITT) population. Sixty-seven patients (the assessable subgroup) either completed both cycles without a major protocol violation (n = 62) or received a platelet transfusion before treatment was discontinued after the first cycle. In the ITT population, rhIL-11 significantly decreased the requirement for platelet transfusions; 27 of 40 (68%) patients who received rhIL-11 did not require transfusions, compared with 15 of 37 (41%) in the placebo group (P = .04). Treatment with rhIL-11 significantly reduced the total number of platelet transfusions required in the assessable subgroup (P = .03) and the time to platelet recovery to more than 50,000/microL in the second cycle (P = .01). Most adverse events associated with rhIL-11 were reversible, mild to moderate in severity, and likely related to fluid retention.
  
  
  CONCLUSIONS
  rhIL-11 is safe and effective in reducing treatment-associated thrombocytopenia and the need for platelet transfusions in patients who undergo dose-intensive chemotherapy, and thus may permit chemotherapy to be administered as planned at intended doses and thereby maximize the potential for a successful outcome.
authors.affiliation: Georgetown University Medical Center, Washington, DC 20007, USA. isaacsc@gunet.georgetown.edu
authors.forename: C
authors.initials: C
authors.lastname: Isaacs
authors.forename: N J
authors.initials: NJ
authors.lastname: Robert
authors.forename: F A
authors.initials: FA
authors.lastname: Bailey
authors.forename: M W
authors.initials: MW
authors.lastname: Schuster
authors.forename: B
authors.initials: B
authors.lastname: Overmoyer
authors.forename: M
authors.initials: M
authors.lastname: Graham
authors.forename: B
authors.initials: B
authors.lastname: Cai
authors.forename: K J
authors.initials: KJ
authors.lastname: Beach
authors.forename: J W
authors.initials: JW
authors.lastname: Loewy
authors.forename: J A
authors.initials: JA
authors.lastname: Kaye
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D017370:Interleukin-11 / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D017713:Platelet Transfusion; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000517:prevention & control* / Q000628:therapy
chemical_list: D017370:Interleukin-11; D011994:Recombinant Proteins; D004317:Doxorubicin; D003520:Cyclophosphamide; C105308:oprelvekin