The effect of decitabine dose modification and myelosuppression on response and survival in patients with myelodysplastic syndromes.
Myelosuppression in myelodysplastic syndromes (MDS) is associated with the hypomethylating agent decitabine. A retrospective pooled analysis of two decitabine clinical trials in patients with MDS conducted Cox regression analyses of red blood cell or platelet dependence, myelosuppression, dose modification, cycle delay or dose reduction, and survival effects. In 182 patients, baseline platelet dependence was a predictor for dose modification, reduction or delay, and death (modification: p=0.006, hazard ratio [HR]=2.04; reduction/delay: p=0.011, HR=2.00; death: p=0.003, HR=1.94). Patients with dose modifications had significantly higher overall response rates versus those with none (22% vs. 10%; p=0.015). Patients with no dose modifications had faster progression to acute myeloid leukemia (AML) versus patients with dose modifications (p=0.004). Without dose modifications, patients tended to drop out due to disease progression or other reasons. Decitabine dose modifications on treatment may indicate response to treatment.
The MD Anderson Cancer Center , Houston, TX , USA.
Elias
E
Jabbour
Guillermo
G
Garcia-Manero
A Megan
AM
Cornelison
Jorge E
JE
Cortes
Farhad
F
Ravandi
Naval
N
Daver
Tapan
T
Kadia
Angela
A
Teng
Hagop
H
Kantarjian
D000208:Acute Disease; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077209:Decitabine; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000473:pathology; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D012189:Retrospective Studies
D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine
Dacogen; decitabine; myelodysplastic syndromes; retrospective study