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.
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