Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996).
This phase 3 prospective randomized trial evaluated the efficacy and long-term safety of erythropoietin (EPO) with or without granulocyte colony-stimulating factor plus supportive care (SC; n = 53) versus SC alone (n = 57) for the treatment of anemic patients with lower-risk myelodysplastic syndromes. The response rates in the EPO versus SC alone arms were 36% versus 9.6%, respectively, at the initial treatment step, 47% in the EPO arm, including subsequent steps. Responding patients had significantly lower serum EPO levels (45% vs 5% responses for levels < 200 mU/mL vs > or = 200 mU/mL) and improvement in multiple quality-of-life domains. With prolonged follow-up (median, 5.8 years), no differences were found in overall survival of patients in the EPO versus SC arms (median, 3.1 vs 2.6 years) or in the incidence of transformation to acute myeloid leukemia (7.5% and 10.5% patients, respectively). Increased survival was demonstrated for erythroid responders versus nonresponders (median, 5.5 vs 2.3 years). Flow cytometric analysis showed that the percentage of P-glycoprotein(+) CD34(+) marrow blasts was positively correlated with longer overall survival. In comparison with SC alone, patients receiving EPO with or without granulocyte colony-stimulating factor plus SC had improved erythroid responses, similar survival, and incidence of acute myeloid leukemia transformation.
Greenberg
Peter L
PL
Stanford University Cancer Center, CA 94305, USA. peterg@stanford.edu
Sun
Zhuoxin
Z
Miller
Kenneth B
KB
Bennett
John M
JM
Tallman
Martin S
MS
Dewald
Gordon
G
Paietta
Elisabeth
E
van der Jagt
Richard
R
Houston
Jessie
J
Thomas
Mary L
ML
Cella
David
D
Rowe
Jacob M
JM
D000368:Aged; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D011379:Prognosis; D011446:Prospective Studies; D011788:Quality of Life; D011994:Recombinant Proteins; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
D011994:Recombinant Proteins; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor