Poster D S, Bruno S, Penta J, Macdonald J S
Cancer Treat Rep. 1981 Jan-Feb;65(1-2):53-6.
Indicine-N-oxide, a pyrrolizidine derivative, was selected for development because of activity in the murine P388 leukemia model. Route and schedule dependency have been demonstrated. It is believed that the antitumor activity of the drug is mediated via antimitotic effects and chromosomal damage. However, the active metabolic species responsible for these antitumor properties is not yet known. The major toxic effect was myelosuppression. Phase I clinical trials have arrived at recommended doses for further study. Colon carcinoma has been found to be possibly responsive, and several tumor types were reported stable during phase I testing. In a single phase II study in refractory leukemia, there were three responses, including one complete response, among seven patients. Phase II studies in all panel tumors are indicated, especially colon carcinoma and leukemias.
牛磺胆酸-N-氧化物，一种吡咯里西啶衍生物，因其在小鼠P388白血病模型中的活性而被选用于开发。已证明其存在给药途径和给药方案依赖性。据信该药物的抗肿瘤活性是通过抗有丝分裂作用和染色体损伤介导的。然而，尚不清楚负责这些抗肿瘤特性的活性代谢产物是什么。主要毒性作用是骨髓抑制。I期临床试验已确定了进一步研究的推荐剂量。已发现结肠癌可能有反应，并且在I期试验期间报告了几种肿瘤类型病情稳定。在一项针对难治性白血病的单组II期研究中，7名患者中有3例有反应，包括1例完全缓解。表明有必要对所有选定肿瘤进行II期研究，尤其是结肠癌和白血病。
