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

SCH 52365 （Temodal）是咪唑四嗪衍生物基的一种口服烷基化剂，具有广谱抗肿瘤活性和较同类化合物更好的毒性。口服替莫达可在4小时内降低烷基转移酶（ATase）活性，并在组织中持续至少24小时。在以前的试验中，每天给药导致ATase活性在5天的治疗过程中逐渐减少。因此，假设在每一天，由于前一天化疗引起的ATase活性降低，对药物的细胞毒性作用的敏感性会增加。这项开放标签、上升多剂量的I期研究旨在表征SCH52365的安全性，并确定采用改良给药方案口服给药给癌患者时的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.