PHASE I STUDY OF CYCLIC ORAL ADMINISTRATION OF SCH61365 (21 OF 28 DAYS)

SCH 52365（Temodal）是一种咪唑四嗪衍生物类口服烷化剂，具有广谱抗肿瘤活性，毒性特征优于类似化合物。 Temodal给药导致烷基转移酶（AT酶）活性在口服给药后4小时内降低，并持续给药至少24小时。 在之前的试验中，每日给药导致在5天治疗过程中ATase活性进行性耗竭。 因此，假设每天对药物的细胞毒性作用的敏感性增加，这是由于前一天化疗诱导的ATase活性降低所致。这项开放标签、递增多次给药的I期研究旨在描述SCH 52365的安全性特征，并确定SCH 52365在采用改良给药方案口服给药至癌症患者时的MTD和DLT。

SCH 52365 (Temodal) is an oral alkylating agent of the imidazotetrazine derivative group which exhibits broad spectrum antitumor activity and a better toxicity profile than similar compounds. Administration of Temodal results in decreased alkytransferase (ATase) activity within 4 hours of an oral dose and persists in tisues for at least 24 hours. Daily administration in previous trials resulted in progressive depletion of ATase activity over the 5 day treatment course. Thus on each day, it is hypothesized that there would be increased sensitivity to the cytoxic effects of the drug resulting from the decrease in ATase activity induced by the prior day's chemotherapy. This open label, rising multiple-dose Phase I study is designed to characterize the safety profile and to determine the MTD and DLT of SCH52365 when administered orally to cancer patients using a modified dosing regimen.