Cobb P W, Havlin K A, Kuhn J G, Craig J B, Harman G S, Luther J S, Turner J N, Weiss G R, Tweedy D A, Koeller J
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7884.
Sel Cancer Ther. 1991 Summer;7(2):85-91. doi: 10.1089/sct.1991.7.85.
Crisnatol is an arylmethylaminopropanediol derivative that has shown promise as an antitumor agent in preclinical testing. In a phase I trial using a monthly six-hour infusion schedule the recommended dose for future phase II trials was found to be 388 mg/m2. Neurologic toxicity was dose-limiting in that trial and correlated with the attainment of a threshold plasma concentration of greater than 4.5 micrograms/ml. In this study we treated 15 patients with escalating doses of crisnatol from 450 mg/m2 to 900 mg/m2 administered at a rate of 50 mg/m2/hr over 9, 12, 15, and 18 hours. Toxicity was mild to moderate at all dose levels. However, serious central nervous system effects were noted in one patient at 900 mg/m2 over 18 hours whose plasma level was 6.5 micrograms/ml. This study has demonstrated higher total doses of crisnatol can be given if the drug is administered as a prolonged infusion in an attempt to avoid high plasma levels of the agent.
克立那托是一种芳基甲基氨基丙二醇衍生物，在临床前试验中已显示出作为抗肿瘤药物的前景。在一项采用每月6小时输注方案的I期试验中，发现未来II期试验的推荐剂量为388mg/m²。在该试验中，神经毒性是剂量限制性的，并且与达到大于4.5微克/毫升的血浆浓度阈值相关。在本研究中，我们以50mg/m²/小时的速率在9、12、15和18小时内对15名患者使用递增剂量的克立那托进行治疗，剂量从450mg/m²增加到900mg/m²。在所有剂量水平下，毒性均为轻度至中度。然而，在一名患者中，以900mg/m²的剂量在18小时内给药，其血浆水平为6.5微克/毫升，出现了严重的中枢神经系统效应。这项研究表明，如果将该药物作为延长输注给药，以避免药物的高血浆水平，可以给予更高的克立那托总剂量。
