echinomycin and Nausea

Twenty-eight evaluable patients with advanced or recurrent squamous-cell carcinoma of the cervix were treated with 1,500 micrograms/m2 of echinomycin every 4 weeks. All patients had prior chemotherapy. Two patients had partial responses (7% response, 95% confidence interval for response of 1 to 24%). The major toxicity was nausea and vomiting. Myelosuppression and other toxicity were modest. Echinomycin, at this dose and schedule, displays minimal activity in patients with squamous-cell carcinoma of the cervix who have had prior chemotherapy.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Drug Evaluation; Echinomycin; Female; Humans; Middle Aged; Nausea; Neoplasm Metastasis; Neoplasm Recurrence, Local; Quinoxalines; Uterine Cervical Neoplasms

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.

Topics: Adult; Aged; Drug Evaluation; Echinomycin; Female; Humans; Infusions, Intravenous; Liver Function Tests; Male; Middle Aged; Nausea; Neoplasms; Platelet Count; Quinoxalines; Thrombocytopenia; Vomiting

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.

Topics: Adult; Aged; Alanine Transaminase; Anaphylaxis; Aspartate Aminotransferases; Droperidol; Drug Administration Schedule; Drug Evaluation; Echinomycin; Female; Hematologic Diseases; Humans; Male; Middle Aged; Nausea; Neoplasms; Quinoxalines