Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes.
OBJECTIVE
Azacitidine (AZA) is effective treatment for myelodysplastic syndromes (MDS) at a dosing schedule of 75 mg/m(2)/d subcutaneously for 7 days every 4 weeks. The initial phase of this ongoing multicenter, community-based, open-label study evaluated three alternative AZA dosing schedules without weekend dosing.


METHODS
MDS patients were randomly assigned to one of three regimens every 4 weeks for six cycles: AZA 5-2-2 (75 mg/m(2)/d subcutaneously for 5 days, followed by 2 days no treatment, then 75 mg/m(2)/d for 2 days); AZA 5-2-5 (50 mg/m(2)/d subcutaneously for 5 days, followed by 2 days no treatment, then 50 mg/m(2)/d for 5 days); or AZA 5 (75 mg/m(2)/d subcutaneously for 5 days).


RESULTS
Of patients randomly assigned to AZA 5-2-2 (n = 50), AZA 5-2-5 (n = 51), or AZA 5 (n = 50), most were French-American-British (FAB) lower risk (refractory anemia [RA]/RA with ringed sideroblasts/chronic myelomonocytic leukemia with < 5% bone marrow blasts, 63%) or RA with excess blasts (30%), and 79 (52%) completed > or = six treatment cycles. Hematologic improvement (HI) was achieved by 44% (22 of 50), 45% (23 of 51), and 56% (28 of 50) of AZA 5-2-2, AZA 5-2-5, and AZA 5 arms, respectively. Proportions of RBC transfusion-dependent patients who achieved transfusion independence were 50% (12 of 24), 55% (12 of 22), and 64% (16 of 25), and of FAB lower-risk transfusion-dependent patients were 53% (nine of 17), 50% (six of 12), and 61% (11 of 18), respectively. In the AZA 5-2-2, AZA 5-2-5, and AZA 5 groups, 84%, 77%, and 58%, respectively, experienced > or = 1 grade 3 to 4 adverse events.


CONCLUSIONS
All three alternative dosing regimens produced HI, RBC transfusion independence, and safety responses consistent with the currently approved AZA regimen. These results support AZA benefits in transfusion-dependent lower-risk MDS patients.
Lyons
Roger M
RM
Cancer Care Centers of South Texas and US Oncology, San Antonio, TX 78229, USA. roger.lyons@usoncology.com
Cosgriff
Thomas M
TM
Modi
Sanjiv S
SS
Gersh
Robert H
RH
Hainsworth
John D
JD
Cohn
Allen L
AL
McIntyre
Heidi J
HJ
Fernando
Indra J
IJ
Backstrom
Jay T
JT
Beach
C L
CL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001374:Azacitidine / Q000008:administration & dosage*; D001803:Blood Transfusion; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000188:drug therapy*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine