Treatment of myelodysplastic syndromes with orally administered N-(2S, 3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucine (ubenimex).
N-(2S, 3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucine (ubenimex) was administered orally, to patients with myelodysplastic syndromes (MDS) and acute leukemia derived from MDS, in a multi-institute study. Out of 77 patients evaluated, one achieved a complete remission, three a good response and two a partial response while 71 failed to respond to a daily oral administration of 30 mg ubenimex. The overall response rate was 7.8% (95% confidence limits; 3.6-16.0%); 7.0% (3.0-15.4%) in 71 MDS and 16.6% (3.0-56.3%) in acute six leukemias derived from MDS. Responses continued for six to 24 (median 10.5) weeks. No serious hematologic, biochemical or clinical toxicity was encountered, except for gastro-intestinal (GI) toxicity in one patient. The present study demonstrated ubenimex not to be generally beneficial for patients with MDS, and not to be recommended as a standard treatment for the disease.
Fukutani
H
H
Department of Medicine, Branch Hospital, Nagoya University School of Medicine.
Naoe
T
T
Saito
H
H
Ohshima
T
T
Omine
M
M
Miura
Y
Y
Mizoguchi
H
H
Kimura
I
I
Tomonaga
M
M
Ohno
R
R
D000208:Acute Disease; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000753:Anemia, Refractory / Q000188:drug therapy; D000754:Anemia, Refractory, with Excess of Blasts / Q000188:drug therapy; D002648:Child; D005260:Female; D006801:Humans; D007930:Leucine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D007938:Leukemia / Q000188:drug therapy; D015477:Leukemia, Myelomonocytic, Chronic / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D011446:Prospective Studies
D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex