title: Safety and efficacy of darbepoetin alpha in previously untreated extensive-stage small-cell lung cancer treated with platinum plus etoposide.
abstract: OBJECTIVE
  A placebo-controlled, double-blind, randomized, phase III study was conducted in patients with extensive-stage small-cell lung cancer receiving first-line platinum-containing chemotherapy to determine if increasing or maintaining hemoglobin concentration with darbepoetin alpha could increase patient survival.
  
  
  METHODS
  Darbepoetin alpha (300 microg) or placebo was administered once per week for 4 weeks then every 3 weeks for up to six cycles of chemotherapy (carboplatin plus etoposide or cisplatin plus etoposide) plus 3 weeks after the last dose of chemotherapy. Patients with disease progression were observed until death or until all patients completed their end-of-study visit and 496 deaths had occurred. The two coprimary end points were change in hemoglobin concentration from baseline to the end of the chemotherapy period and overall survival; statistical testing of survival was done if change in hemoglobin was significant at P < .05.
  
  
  RESULTS
  The study enrolled 600 patients. Patients' hemoglobin levels dropped due to the myelosuppressive chemotherapy; however, treatment with darbepoetin alpha maintained hemoglobin levels significantly higher than placebo (P < .001). There was no statistically significant difference in overall survival between the treatment groups (hazard ratio [HR], 0.93; 95% CI, 0.78 to 1.11; P = .431). As expected, darbepoetin alpha was associated with a higher incidence of thromboembolic events (darbepoetin alpha, 9%; placebo, 5%). The transfusion risk was lower in the darbepoetin versus placebo group (HR, 0.40; 95% CI, 0.29 to 0.55).
  
  
  CONCLUSIONS
  The results of this study did not demonstrate improved survival after treatment with darbepoetin alpha; however, they reinforce the benefit of erythropoiesis-stimulating agents in reducing transfusions and their neutral impact on survival in patients with chemotherapy-induced anemia.
authors.affiliation: Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. robert.pirker@meduniwien.ac.at
authors.forename: Robert
authors.initials: R
authors.lastname: Pirker
authors.forename: Rodryg A
authors.initials: RA
authors.lastname: Ramlau
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schuette
authors.forename: Petr
authors.initials: P
authors.lastname: Zatloukal
authors.forename: Irene
authors.initials: I
authors.lastname: Ferreira
authors.forename: Tom
authors.initials: T
authors.lastname: Lillie
authors.forename: Johan F
authors.initials: JF
authors.lastname: Vansteenkiste
mesh_terms: D000368:Aged; D000740:Anemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018288:Carcinoma, Small Cell / Q000097:blood* / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D000068256:Darbepoetin alfa; D004311:Double-Blind Method; D004921:Erythropoietin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006397:Hematinics / Q000627:therapeutic use; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015996:Survival Rate
chemical_list: D006397:Hematinics; D006454:Hemoglobins; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D016190:Carboplatin; D002945:Cisplatin