Phase I study of echinomycin administered on an intermittent bolus schedule.
We have conducted a phase I study of the cyclic peptide echinomycin (Quinomycin A) on a schedule of administration of once every 4 weeks. Ten dose levels between 20 and 1800 micrograms/m2 were studied. Acute gastrointestinal toxicity, thrombocytopenia, and transient elevations of serum transaminases occurred at doses of greater than or equal to 1000 micrograms/m2. Gastrointestinal toxicity was severe and dose-limiting in several patients at doses of 1800 micrograms/m2. Thrombocytopenia was erratic, but generally increased with drug doses. Platelet count nadirs occurred 5-10 days after administration. Hepatic toxicity was reflected in transient elevations of serum transaminases without hyperbilirubinemia. Three patients experienced apparent anaphylactic reactions to doses of 1500 micrograms/m2. The maximum tolerated single dose of echinomycin was 1800 micrograms/m2. A starting phase II dose of 1500 micrograms/m2 is recommended.
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000032:analysis; D000707:Anaphylaxis / Q000139:chemically induced; D001219:Aspartate Aminotransferases / Q000032:analysis; D004329:Droperidol / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004448:Echinomycin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control; D009369:Neoplasms / Q000188:drug therapy*; D011810:Quinoxalines / Q000008:administration & dosage*
D011810:Quinoxalines; D004448:Echinomycin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D004329:Droperidol