Phase I trial of echinomycin (NSC 526417), a bifunctional intercalating agent, administered by 24-hour continuous infusion.
Echinomycin was administered to 43 patients with advanced cancer in escalating doses ranging from 60 to 2128 mcg/m2. The dose-limiting toxicity of echinomycin administered as a 24-h continuous infusion every 28 days was nausea and vomiting beginning at the end of the 24 h infusion and lasting from 3 to 8 days. Other toxicities included sporadic thrombocytopenia and biochemical evidence of liver dysfunction characterized by elevations in SGOT. Peripheral vein phlebitis was noted in 100% of patients, and watery diarrhea of 24-48-h duration was noted in 7% of patients. The maximally tolerated dose of echinomycin was 2128 mcg/m2. The recommended dose for phase II trials utilizing the 24-h continuous infusion schedule is 1600 mcg/m2 repeated every 28 days with pretreatment antiemetics.
Kuhn
J G
JG
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7765.
Von Hoff
D D
DD
Hersh
M
M
Melink
T
T
Clark
G M
GM
Weiss
G R
GR
Coltman
C A
CA
D000328:Adult; D000368:Aged; D004341:Drug Evaluation; D004448:Echinomycin / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy; D010976:Platelet Count / Q000187:drug effects; D011810:Quinoxalines / Q000008:administration & dosage*; D013921:Thrombocytopenia / Q000139:chemically induced; D014839:Vomiting / Q000139:chemically induced
D011810:Quinoxalines; D004448:Echinomycin