[Clinical trial of SM-108 in myeloproliferative disorders].
SM-108 (4-carbamoylimidazolium-5-olate) is a new purine antagonist which blocks IMP dehydrogenase, the key enzyme of de novo GMP biosynthesis. Eleven patients were entered into a clinical study of SM-108 for the treatment of myeloproliferative disorders. These included 10 cases of chronic myelogenous leukemia (CML) and one case of essential thrombocythemia (ET). Two cases of CML had received prior chemotherapy. SM-108 was given orally at a dose of 400-600mg/m2 daily. Of nine evaluable cases, four cases of CML achieved complete responses and two cases of CML achieved partial responses (response rate = 66.7%). The duration of drug action was short, and the daily dosage required adjustment at frequent intervals. Long-term response without therapy has not been seen with SM-108 in CML. There was no response in the case of ET. The side effects included constipation (1/11), diarrhea (1/11) and mild hepatic toxicity (1/11). No cardiac or renal toxicity was observed.
Nishikawa
M
M
2nd Dept. of Internal Medicine, Mie University School of Medicine.
Morita
K
K
Sekine
T
T
Takeda
M
M
Tamaki
S
S
Katayama
N
N
Kobayashi
T
T
Mukai
K
K
Tanaka
H
H
Minami
N
N
D000328:Adult; D000368:Aged; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000188:drug therapy*; D013920:Thrombocythemia, Essential / Q000188:drug therapy*
D007093:Imidazoles; C033758:4-carbamoylimidazolium 5-olate