Results of a phase II study of thalidomide and azacitidine in patients with clinically advanced myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and low blast count acute myeloid leukemia (AML).
Single agent azacitidine or immunomodulatory drugs are effective in myelodysplastic syndrome (MDS), with differing target mechanisms and toxicities. Objectives of this ALLG MDS3 study in clinically advanced MDS, AMML and low blast AML were to establish safety, response and quality of life of azacitidine and thalidomide. Patients received azacitidine (75mg/m2/d sc 7days every 28 days), and oral thalidomide up to 100mg/d for maximum 12months. Eighty patients registered; median age 68 years (range 42-82), 49% IPSS int2-high. With 36.5 months follow up, patients received median 9 cycles azacitidine, 6.1mths thalidomide. Nonhematologic toxicity grade 3+ in 85%, commonly infections. Overall response rate was 63%; 26% CR were unaffected by IPSS. Median response duration 26.3months; overall survival was 28.1months. This combination azacitidine and thalidomide in clinically advanced MDS, CMML and low-blast AML was tolerable without unexpected toxicity and encouraging responses support further investigation of combination approaches with hypomethylating agent and immunomodulatory drug.
a Department of Haematology , Cabrini Health , Melbourne , Australia.|b Department of Haematology , Peter MacCallum Cancer Centre , Melbourne , Australia.|c Melbourne University , Melbourne , Australia.
Melita
M
Kenealy
d Royal Adelaide Hospital , Adelaide , Australia.
Nigel
N
Patton
e St Vincent's Hospital Melbourne , Australia.
Robin
R
Filshie
f Greenslopes Private Hospital , Brisbane , Australia.
Andrew
A
Nicol
g St George Hospital , Sydney , Australia.
Shir-Jing
SJ
Ho
h Department of Haematology , Prince of Wales Hospital and University of New South Wales , Sydney , Australia.
Mark
M
Hertzberg
i Princess Alexandra Hospital , Brisbane , Australia.
Tony
T
Mills
j Canberra Hospital , Canberra , Australia.
Ian
I
Prosser
b Department of Haematology , Peter MacCallum Cancer Centre , Melbourne , Australia.
Emma
E
Link
b Department of Haematology , Peter MacCallum Cancer Centre , Melbourne , Australia.
Linda
L
Cowan
k Australasian Leukaemia and Lymphoma Group , Melbourne , Australia.
Diana
D
Zannino
b Department of Haematology , Peter MacCallum Cancer Centre , Melbourne , Australia.|c Melbourne University , Melbourne , Australia.
John F
JF
Seymour
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D015477:Leukemia, Myelomonocytic, Chronic / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011787:Quality of Health Care; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage; D016896:Treatment Outcome
D013792:Thalidomide; D001374:Azacitidine
Azacitidine; clinical trial; myelodysplastic syndrome (MDS); thalidomide