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

SCH 52365(替莫达尔)是咪唑四嗪类化合物的一种口服烷基化试剂，具有广谱的抗肿瘤活性和比同类化合物更好的毒性。口服Temodal后4小时内，可导致碱性转移酶(ATase)活性降低，并可在组织中持续至少24小时。在之前的试验中，每日给药导致在5天的治疗过程中ATase活性逐渐耗尽。因此，在每一天，假设对药物的细胞毒性效应的敏感性会增加，这是由于前一天化疗导致ATase活性下降所致。这项开放标签的RISTING多剂量I期研究旨在描述SCH52365的安全性，并确定SCH52365在使用改进的剂量方案口服给药时的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.