Stewart J A, Low J B, Roberts J D, Blow A
Vermont Regional Cancer Center, University of Vermont, Burlington 05401.
Cancer. 1991 Dec 15;68(12):2550-4. doi: 10.1002/1097-0142(19911215)68:12<2550::aid-cncr2820681203>3.0.co;2-q.
Didemnin B is a depsipeptide extracted from the marine tunicate Trididemnin cyanophorum. This agent is a potent inhibitor of L1210 growth in vitro and has activity against murine B16 melanoma, P388 leukemia, and M5076 sarcoma in vivo. The results of preclinical toxicologic tests demonstrated abnormalities in clotting parameters thought to be secondary to drug-induced liver dysfunction. Thirty-five patients with advanced cancer received didemnin B according to a 5-day bolus schedule with dose levels ranging from 0.03 to 2.00 mg/m2/d. The dose-limiting toxicity was nausea and vomiting. Sporadic elevation of the hepatic enzyme level occurred but was not dose limiting. Two patients had anaphylactic symptoms possibly related to the 5% polyoxyethylated castor oil (Cremophor EL, BASF, Ludwigshafen, Germany) vehicle during the drug infusion. Clinical bleeding was not observed and myelosuppression was not significant. No partial or complete tumor responses were seen. The recommended Phase II dose for the 5-day schedule is 1.6 mg/m2/d.
地棘蛙素B是从海洋被囊动物蓝皮三毛海鞘中提取的一种缩肽。该药物在体外是L1210生长的强效抑制剂，在体内对小鼠B16黑色素瘤、P388白血病和M5076肉瘤具有活性。临床前毒理学试验结果显示凝血参数异常，认为这是药物诱导的肝功能障碍的继发表现。35例晚期癌症患者按照5天推注方案接受地棘蛙素B治疗，剂量水平为0.03至2.00mg/m²/天。剂量限制性毒性为恶心和呕吐。肝酶水平偶尔升高，但并非剂量限制性因素。两名患者在药物输注期间出现可能与5%聚氧乙烯蓖麻油（德国路德维希港巴斯夫公司的克列莫佛EL）载体相关的过敏症状。未观察到临床出血情况，骨髓抑制也不显著。未观察到部分或完全肿瘤缓解。5天方案的推荐II期剂量为1.6mg/m²/天。
