Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy.
BACKGROUND
Patients receiving chemotherapy often develop anemia. Darbepoetin alfa (Aranesp(TM)) is an erythropoiesis-stimulating glycoprotein that has been shown, in dose-finding studies, to be safe and clinically active when administered to patients with cancer every 1, 2, or 3 weeks. This phase III study compared the safety and efficacy of darbepoetin alfa with placebo in patients with lung cancer receiving chemotherapy.


METHODS
In this multicenter, double-blind, placebo-controlled study, 320 anemic patients (hemoglobin <or=11.0 g/dL) were randomly assigned to receive darbepoetin alfa or placebo injections weekly for 12 weeks. The 297 patients who completed at least the first 28 days of study were assessed for red blood cell transfusions, the primary endpoint. Patients were also assessed for hemoglobin concentration (i.e., hematopoietic response), adverse events, antibody formation to darbepoetin alfa, hospitalizations, Functional Assessment of Cancer Therapy (FACT)-Fatigue score, and disease outcome. Efficacy endpoints were assessed using Kaplan-Meier analyses, Cox proportional hazards analyses, and chi-square tests where appropriate. All statistical tests were two-sided.


RESULTS
Patients receiving darbepoetin alfa required fewer transfusions (27% versus 52%; mean difference = 25%; 95% confidence interval [CI] = 14% to 36%; P<.001), required fewer units of blood (0.67 versus 1.92; mean difference = 1.25, 95% CI = 0.65 to 1.84; P<.001), had more hematopoietic responses (66% versus 24%; mean difference = 42%; 95% CI = 31% to 53%; P<.001), and had better improvement in FACT-Fatigue scores (56% versus 44% overall improvement; 32% versus 19% with >or=25% improvement; mean difference = 13%; 95% CI = 2% to 23%, P =.019) than patients receiving placebo. Patients receiving darbepoetin alfa did not appear to have any untoward effect in disease outcome and did not develop antibodies to the drug. Adverse events were similar between the groups.


CONCLUSIONS
Patients with chemotherapy-associated anemia can safely and effectively be treated with weekly darbepoetin alfa therapy. Darbepoetin alfa decreased blood transfusion requirements, increased hemoglobin concentration, and decreased fatigue. Although no conclusions can be drawn about survival from this study, the potential salutary effect on disease outcome warrants further investigation in a prospectively designed study.
Vansteenkiste
Johan
J
Respiratory Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium. johan.vansteenkiste@uz.kuleuven.ac.be
Pirker
Robert
R
Massuti
Bartomeu
B
Barata
Fernando
F
Font
Albert
A
Fiegl
Michael
M
Siena
Salvatore
S
Gateley
Jenni
J
Tomita
Dianne
D
Colowick
Alan B
AB
Musil
Jaromir
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D000068256:Darbepoetin alfa; D018450:Disease Progression; D004311:Double-Blind Method; D017707:Erythrocyte Transfusion / Q000706:statistics & numerical data*; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D005221:Fatigue / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006801:Humans; D007902:Length of Stay / Q000706:statistics & numerical data; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010343:Patient Admission / Q000706:statistics & numerical data; D017671:Platinum Compounds / Q000009:adverse effects; D011795:Surveys and Questionnaires; D016019:Survival Analysis; D016896:Treatment Outcome
D017671:Platinum Compounds; D004921:Erythropoietin; D000068256:Darbepoetin alfa