Phase I clinical trial of ethyl 6-deoxy-3,5-di-O-methyl 6-(3 methyl-3-nitrosoureido)-alpha-D-glucofuranoside (CGP 6809).
A phase I study of single i.v. doses of a new sugar containing nitrosourea 6-deoxy-3,5 di-O-methyl 6-(3 methyl-3-nitrosoureido)-alpha-D-glucofuranoside (CGP 6809, EDMN) has been carried out in 47 patients with advanced solid tumors. Nine dose levels between 200 and 4500 mg/m2 were examined. Nausea and vomiting were seen in most patients but were controlled with antiemetics. Myelosuppression was minimal. The dose-limiting toxicity was hepatotoxicity, occurring early (peak at days 2-4) and resolving rapidly. No cumulative toxicity was seen with an every 6 weeks schedule. Other toxicities were abdominal pain, diarrhea, arm pain, restlessness, and headache. Pharmacokinetic studies in 20 patients using an HPLC assay and in 5 patients using [14C]EDMN showed a short half-life, rapid plasma clearance, rapid metabolism, and minimal excretion of unchanged drug. There was one partial response in a patient with colon carcinoma. The recommended dose for phase II studies in 3750 mg/m2 every 6 weeks.
Creaven
P J
PJ
Madajewicz
S
S
Cowens
J W
JW
Plager
J E
JE
Pendyala
L
L
Mittelman
A
A
Petrelli
N
N
Karakousis
C
C
Huben
R
R
Takita
H
H
D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007700:Kinetics; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy*; D009607:Nitrosourea Compounds / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced
D009607:Nitrosourea Compounds; C035871:CGP 6809