title: Clinical trial simulation of a 200-microg fixed dose of darbepoetin alfa in chemotherapy-induced anemia.
abstract: Our objective was to assess, using clinical trial simulation, the feasibility of a fixed 200-microg dose of darbepoetin alfa (Aranesp) administered every 2 weeks in chemotherapy-induced anemia. A pharmacokinetic/pharmacodynamic model was developed using clinical data from 547 cancer patients who received darbepoetin alfa at various doses and schedules. Monte Carlo simulations were performed for weight-based (3 microg/kg every 2 weeks) and fixed-dose (200 microg every 2 weeks) regimens and were compared with observed clinical data. Mean hemoglobin changes from baseline to end of treatment were +1.61 g/dL, +1.83 g/dL, and +1.79 g/dL for observed data, the weight-based simulation, and the fixed-dose simulation, respectively. The rates of required transfusions (hemoglobin < or = 8 g/dL) were also similar between groups. For patients between 45 and 95 kg (over 90% of the population), the impact of a fixed dose on mean hemoglobin change was negligible. There was a slight weight effect at body weight extremes (< 45 kg and > 95 kg). Clinical outcomes from simulations of weight-based andfixed dosing of darbepoetin alfa were similar to those of observed weight-based data. Given the weight distribution of a typical cancer population, the majority would be expected to benefit equally from weight-based and fixed-dose darbepoetin alfa in the amelioration of chemotherapy-induced anemia.
authors.affiliation: Amgen Inc., Thousand Oaks, California 91320-1799, USA. njumbe@amgen.com
authors.forename: Nelson
authors.initials: N
authors.lastname: Jumbe
authors.forename: Bin
authors.initials: B
authors.lastname: Yao
authors.forename: Robert
authors.initials: R
authors.lastname: Rovetti
authors.forename: Gregory
authors.initials: G
authors.lastname: Rossi
authors.forename: Anne C
authors.initials: AC
authors.lastname: Heatherington
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy*; D001835:Body Weight / Q000187:drug effects; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy; D002986:Clinical Trials as Topic / Q000379:methods*; D003198:Computer Simulation; D000068256:Darbepoetin alfa; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000097:blood / Q000188:drug therapy; D005833:Genital Neoplasms, Female / Q000097:blood / Q000188:drug therapy; D005834:Genital Neoplasms, Male / Q000097:blood / Q000188:drug therapy; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009010:Monte Carlo Method
chemical_list: D006454:Hemoglobins; D004921:Erythropoietin; D000068256:Darbepoetin alfa