title: Darbepoetin alpha for the treatment of anemia in patients with active cancer not receiving chemotherapy or radiotherapy: results of a phase III, multicenter, randomized, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  The efficacy and safety of darbepoetin alpha (DA) for treating patients with active cancer and anemia not receiving or planning to receive cytotoxic chemotherapy or myelosuppressive radiotherapy was evaluated.
  
  
  METHODS
  Patients with active cancer and anemia not receiving or planning to receive chemotherapy or radiotherapy were enrolled onto a phase III, multicenter, randomized, placebo-controlled study and administered placebo or DA 6.75 microg/kg every 4 weeks (Q4W) for up to 16 weeks with a 2-year follow-up for survival. Patients who completed 16 weeks of treatment could receive the same treatment as randomized Q4W for an additional 16 weeks. The primary end point was all occurrences of transfusions from weeks 5 through 17; safety end points included incidence of adverse events and survival.
  
  
  RESULTS
  The incidence of transfusions between weeks 5 and 17 was lower in the DA group but was not statistically significantly different from that of placebo. DA was associated with an increased incidence of cardiovascular and thromboembolic events and more deaths during the initial 16-week treatment period. Long-term survival data demonstrated statistically significantly poorer survival in patients treated with DA versus placebo (P = .022). This effect varied by baseline covariates including, sex, tumor type, and geographic region; statistical significance diminished (P = .12) when the analysis was adjusted for baseline imbalances or known prognostic factors.
  
  
  CONCLUSIONS
  DA was not associated with a statistically significant reduction in transfusions. Shorter survival was observed in the DA arm; thus, this study does not support the use of erythropoiesis-stimulating agents in this subset of patients with anemia of cancer.
authors.affiliation: South Carolina Oncology Associates, Columbia, SC, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Smith
authors.forename: Matti S
authors.initials: MS
authors.lastname: Aapro
authors.forename: Heinz
authors.initials: H
authors.lastname: Ludwig
authors.forename: Tamás
authors.initials: T
authors.lastname: Pintér
authors.forename: Martin
authors.initials: M
authors.lastname: Smakal
authors.forename: Tudor E
authors.initials: TE
authors.lastname: Ciuleanu
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Tom
authors.initials: T
authors.lastname: Lillie
authors.forename: John A
authors.initials: JA
authors.lastname: Glaspy
mesh_terms: D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D000068256:Darbepoetin alfa; D004311:Double-Blind Method; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy; D010919:Placebos; D011879:Radiotherapy Dosage; D015996:Survival Rate
chemical_list: D006397:Hematinics; D010919:Placebos; D004921:Erythropoietin; D000068256:Darbepoetin alfa