PH I: TWO WEEK PO ADMINISTRATION SCH 66336 ADVANCED CANCER

目的：这是一项I期、开放、递增的多剂量研究，旨在描述SCH 66336的安全性，并确定SCH 100口服给成年晚期癌症患者时的最大耐受量和剂量限制毒性。SCH 66336是一种ftp抑制剂，代表了一类新的抗肿瘤化合物。它是由先灵葆雅公司开发的，尚未在人体上进行测试。方法：单次口服SC-66336，观察24小时(仅限L周期)。然后，受试者将连续13天每天接受两次SC 66336。在每个剂量水平，在第1天和第14天进行药代动力学评估。患者在临床研究中心接受第一次服药的监测和药代动力学，并在第14天重复药物动力学。结果：3例患者出现剂量限制性毒性(肌酐升高、乏力、恶心、腹泻)。DLT达到300毫克。主要的毒性似乎是腹泻和疲劳，在停止研究药物后，这些毒性很快就可以逆转。大多数患者出现2级症状。在赫维茨博士的要求下，研究赞助商批准了另外4名患者的延期，试验剂量为200毫克。未来计划：没有招募更多的患者，尽管患者仍在研究中接受治疗。

Purpose: This is a phase I, open-label, rising, multiple-dose study designed to characterize the safety profile and determine the maximally-tolerated dose and dose-limiting toxicity of SCH 66336 when administered orally to adult patients with advanced cancer. SCH 66336 is an FTP inhibitor and represents a new class of antineoplastic compounds. It was developed by Schering Plough and has not yet been tested in humans. Methods: Patients receive a single-dose of SC 66336 followed by a 24 hour observation period (cycle l only). Subjects will then receive SC 66336 twice daily for 13 consecutive days. At each dose level, pharmacokinetic evaluations are performed on day 1 and day 14. Patients are admitted to the Clinical Research Center for monitoring and pharmacokinetics for their first dose and repeat pharmacokinetics on day 14. Results: Three patients have experienced dose-limiting toxicity (elevated creatinine, fatigue, nausea, diarrhea). DLT was reached at 300 mg. The primary toxicities appear to be diarrhea and fatigue, which are quickly reversible after discontinuing study drug. Most patients experienced grade 2 symptoms. At Dr Hurwitz' request, the study sponsor granted an extension for an additional four patients enrolled at 200 mg. Future Plans: No further patients are being recruited, although patients are still being treated on study.