PH I: TWO WEEK PO ADMINISTRATION SCH 66336 ADVANCED CANCER

目的：这是一项I期、开放标签、上升剂量、多剂量研究，旨在确定晚期癌症成年患者口服SCH 66336的安全性，并确定其最大耐受剂量和剂量限制毒性。SCH 66336是一种FTP抑制剂，是一类新的抗肿瘤化合物。它是由先灵葆雅开发的，尚未在人体中进行测试。方法：患者接受单剂量SC 66336，随后24小时观察期（仅第1周期）。受试者将连续13天每天两次接受SC 66336治疗。在每个剂量水平下，在第1天和第14天进行药代动力学评估。患者入住临床研究中心进行第一次给药和第14天重复药代动力学监测和药代动力学。结果：3例患者出现剂量限制性毒性（肌酐升高、疲劳、恶心、腹泻）。DLT达到300 mg。主要的毒性似乎是腹泻和疲劳，在停止研究药物后迅速可逆。大多数患者出现2级症状。在赫尔维茨博士的要求下，研究发起人批准了另外4名200毫克剂量患者的延期。未来计划：不再招募更多患者，但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.