IN VITRO DRUG TESTING FOR LIMITED SCLC AND PHASE I DRUG DEVELOPMENT

有限 SCLC 的体外药物测试和 I 期药物开发

• 批准号: 3853211
• 负责人: B E JOHNSON
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3853211
• 关键词: antineoplastics; cis platinum compound; clinical trials; combination cancer therapy; dosage; drug adverse effect; drug design /synthesis /production; drug screening /evaluation; human subject; longitudinal human study; lung neoplasms; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; neoplasm /cancer radiation therapy; neoplastic cell; small cell lung cancer; tissue /cell culture

A protocol combining twice a day radiotherapy plus VP 16 and cisplatin for limited stage small cell lung cancer continues. Thirty-eight patients have been entered onto study and 28 of 36 (78%) patients who have completed therapy have achieved a complete remission. The projected median survival is 30 months with a median potential follow-up of 27 months. One patient has died from combined modality pneumonitis. A phase I trial using dihydrolenperone, an agent identified as being active against human lung cancer by the dosage levels. The principle side effects have been somnolence and hypotension in all patients. Six patients have had to stop therapy because of somnolence and none because of hypotension. There have been no objective responses to date. In vitro testing with dihydrolenperone showed 50% inhibition of growth of non-small cell and small cell lung cancer lines at 25-165 ug/ml. Pharmacokinetic determinations show peak absorption at 3-5 hours and plasma levels were more than 100 fold less than the levels where in vitro activity against lung cancer cell lines was observed. From this studies we conclude that the HTCFA has identified a compound with novel side effects, the maximum tolerated dose is 50 mg per square meter, and achievable plasma levels are much less than that required for in vitro activity.

一天两次放疗加VP 16和顺铂的方案 局限期小细胞肺癌的治疗仍在继续。 三十八 36例患者中有28例（78%） 已完成治疗并达到完全缓解。 的 预计中位生存期为30个月，中位潜在随访期 27个月。 1例患者死于联合模式肺炎。 一项使用二氢仑哌隆的I期试验， 对人肺癌的有效剂量水平。 原则 所有患者的副作用是嗜睡和低血压。六 患者因为嗜睡而不得不停止治疗， 低血压迄今为止，尚未收到任何客观的答复。 用二氢仑哌隆进行的体外试验显示， 非小细胞肺癌和小细胞肺癌细胞系在25-165微克/毫升。 药代动力学测定显示在3-5小时达到峰值吸收， 血浆水平比在实验中的水平低100倍以上。 观察到对肺癌细胞系的体外活性。 从这项研究中，我们得出结论，HTCFA已经确定了一种化合物， 伴随新的副作用，最大耐受剂量为50 mg/平方 米，可达到的血浆水平远远低于所需的 体外活性。