title: Phase II study of two dose schedules of C.E.R.A. (Continuous Erythropoietin Receptor Activator) in anemic patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy.
abstract: BACKGROUND
  C.E.R.A. (Continuous Erythropoietin Receptor Activator) is an innovative agent with unique erythropoietin receptor activity and prolonged half-life. This study evaluated C.E.R.A. once weekly (QW) or once every 3 weeks (Q3W) in patients with anemia and advanced non-small cell lung cancer (NSCLC) receiving chemotherapy.
  
  
  METHODS
  In this Phase II, randomized, open-label, multicenter, dose-finding study, patients (n = 218) with Stage IIIB or IV NSCLC and hemoglobin (Hb) <or= 11 g/dL were randomized to one of six treatment groups of C.E.R.A. administered subcutaneously for 12 weeks: 0.7, 1.4, or 2.1 microg/kg QW or 2.1, 4.2, or 6.3 microg/kg Q3W. Primary endpoint was average Hb level between baseline and end of initial treatment (defined as last Hb measurement before dose reduction or transfusion, or the value at week 13). Hematopoietic response (Hb increase >or= 2 g/dL or achievement of Hb >or= 12 g/dL with no blood transfusion in the previous 28 days determined in two consecutive measurements within a 10-day interval) was also measured.
  
  
  RESULTS
  Dose-dependent Hb increases were observed, although the magnitude of increase was moderate. Hematopoietic response rate was also dose dependent, achieved by 51% and 62% of patients in the 4.2 and 6.3 microg/kg Q3W groups, and 63% of the 2.1 mug/kg QW group. In the Q3W group, the proportion of early responders (defined as >or= 1 g/dL increase in Hb from baseline during the first 22 days) increased with increasing C.E.R.A. dose, reaching 41% with the highest dose. In the 6.3 microg/kg Q3W group, 15% of patients received blood transfusion. There was an inclination for higher mean Hb increases and lower transfusion use in the Q3W groups than in the QW groups. C.E.R.A. was generally well tolerated.
  
  
  CONCLUSIONS
  C.E.R.A. administered QW or Q3W showed clinical activity and safety in patients with NSCLC. There were dose-dependent increases in Hb responses. C.E.R.A. appeared to be more effective when the same dose over time was given Q3W than QW, with a suggestion that C.E.R.A. 6.3 microg/kg Q3W provided best efficacy in this study. However, further dose-finding studies using higher doses are required to determine the optimal C.E.R.A. dose regimen in cancer patients receiving chemotherapy.
authors.affiliation: Royal Victoria Hospital, McGill University Health Center, Montreal, Quebec, Canada. vera.hirsh@muhc.mcgill.ca
authors.forename: Vera
authors.initials: V
authors.lastname: Hirsh
authors.forename: John
authors.initials: J
authors.lastname: Glaspy
authors.forename: Paul
authors.initials: P
authors.lastname: Mainwaring
authors.forename: Christian
authors.initials: C
authors.lastname: Manegold
authors.forename: Rodryg
authors.initials: R
authors.lastname: Ramlau
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Eid