Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B.
OBJECTIVE
Patients with high-risk myelodysplastic syndrome (MDS) have high mortality from bone marrow failure or transformation to acute leukemia. Supportive care is standard therapy. We previously reported that azacitidine (Aza C) was active in patients with high-risk MDS.


METHODS
A randomized controlled trial was undertaken in 191 patients with MDS to compare Aza C (75 mg/m(2)/d subcutaneously for 7 days every 28 days) with supportive care. MDS was defined by French-American-British criteria. New rigorous response criteria were applied. Both arms received transfusions and antibiotics as required. Patients in the supportive care arm whose disease worsened were permitted to cross over to Aza C.


RESULTS
Responses occurred in 60% of patients on the Aza C arm (7% complete response, 16% partial response, 37% improved) compared with 5% (improved) receiving supportive care (P <.001). Median time to leukemic transformation or death was 21 months for Aza C versus 13 months for supportive care (P =.007). Transformation to acute myelogenous leukemia occurred as the first event in 15% of patients on the Aza C arm and in 38% receiving supportive care (P =.001). Eliminating the confounding effect of early cross-over to Aza C, a landmark analysis after 6 months showed median survival of an additional 18 months for Aza C and 11 months for supportive care (P =.03). Quality-of-life assessment found significant major advantages in physical function, symptoms, and psychological state for patients initially randomized to Aza C.


CONCLUSIONS
Aza C treatment results in significantly higher response rates, improved quality of life, reduced risk of leukemic transformation, and improved survival compared with supportive care. Aza C provides a new treatment option that is superior to supportive care for patients with the MDS subtypes and specific entry criteria treated in this study.
Silverman
Lewis R
LR
Division of Medical Oncology, Mount Sinai School of Medicine and Memorial Sloan-Kettering Cancer Center, Box 1129, One Gustave L. Levy Place, New York, NY 10029, USA. lewis.silverman@mssm.edu
Demakos
Erin P
EP
Peterson
Bercedis L
BL
Kornblith
Alice B
AB
Holland
Jimmie C
JC
Odchimar-Reissig
Rosalie
R
Stone
Richard M
RM
Nelson
Douglas
D
Powell
Bayard L
BL
DeCastro
Carlos M
CM
Ellerton
John
J
Larson
Richard A
RA
Schiffer
Charles A
CA
Holland
James F
JF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D001772:Blood Cell Count; D001853:Bone Marrow / Q000473:pathology; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D015448:Leukemia, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D012074:Remission Induction; D012307:Risk Factors; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine