Harvey J H, McFadden M, Andrews W G, Byrne P J, Ahlgren J D, Woolley P V
Cancer Treat Rep. 1985 Dec;69(12):1365-8.
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.
我们进行了一项关于环肽放线菌素（链黑菌素A）的I期研究，给药方案为每4周一次。研究了20至1800微克/平方米之间的10个剂量水平。在剂量大于或等于1000微克/平方米时，出现了急性胃肠道毒性、血小板减少症以及血清转氨酶短暂升高。在1800微克/平方米的剂量下，几名患者出现了严重的胃肠道毒性，且该毒性为剂量限制性毒性。血小板减少症情况不稳定，但一般随药物剂量增加而加重。血小板计数最低点出现在给药后5至10天。肝毒性表现为血清转氨酶短暂升高，无高胆红素血症。3名患者在1500微克/平方米的剂量下出现了明显的过敏反应。放线菌素的最大耐受单剂量为1800微克/平方米。建议II期起始剂量为1500微克/平方米。
