PH I: TWO WEEK PO ADMINISTRATION SCH 66336 ADVANCED CANCER

目的：这是一项I期、开放标签、递增、多次给药研究，旨在描述晚期癌症成人患者口服SCH 66336的安全性特征，并确定SCH 66336的最大耐受剂量和剂量限制性毒性。SCH 66336是一种FTP抑制剂，代表了一类新的FTP化合物。它是由先灵葆雅开发的，尚未在人类身上进行测试。方法：患者接受SC 66336单次给药，随后为24小时观察期（仅周期1）。然后，受试者将接受SC 66336每日两次，连续13天。在每个剂量水平下，在第1天和第14天进行药代动力学评价。将患者送入临床研究中心进行第一次给药的监测和药代动力学，并在第14天重复药代动力学。结果：3例患者出现剂量限制性毒性（肌酐升高、疲乏、恶心、腹泻）。在300 mg时达到DLT。主要毒性似乎是腹泻和疲乏，在停用研究药物后可迅速逆转。大多数患者出现2级症状。应Hurwitz博士的要求，研究申办者批准了另外4例200 mg入组患者的延长期。未来计划：尽管患者仍在接受研究治疗，但未招募更多患者。

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.