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

一天两次放疗加VP-16和顺铂方案治疗 局限性小细胞肺癌仍在继续。29名患者 已进入研究，26名患者中有19名(73%)已完成 治疗已经取得了完全缓解。预测的中位生存期 已超过2年，29名患者中有11名存活且无癌症 进展，潜在随访中位数为28个月。一名患者患上了 死于混合性肺炎。 使用二氢兰培酮的I期试验，一种被确认为有效的药物 人肿瘤集落形成实验(HTCFA)抗人肺癌的研究 已经完成了。对32名患者进行了6种剂量的研究。 级别。主要的副作用是嗜睡和低血压。 所有病人。六名患者因嗜睡而不得不停止治疗 没有一例是因为低血压。目前还没有得到客观的回应 约会。 二氢香草酮的体外试验显示，对人骨肉瘤细胞的生长有50%的抑制作用 非小细胞和小细胞。肺癌细胞系为25-165微克/毫升。 药代动力学测定显示吸收高峰在3-5小时，血浆 水平比体外活性水平低100多倍 观察其对肺癌细胞株的抑制作用。 从这项研究中我们得出结论，HTCFA已经确定了一种化合物与 新的副作用，最大耐受量为每平方米50毫克， 可达到的血浆水平远远低于体外培养所需的水平 活动。

A protocol combining twice a day radiotherapy plus VP 16 and cisplatin for limited stage small cell lung cancer continues. Twenty-nine patients have been entered onto study and 19 of 26 (73%) patients who have completed therapy have achieved a complete remission. The projected median survival is greater than 2 years and 11 of 29 patients are alive and free of cancer progression with a median potential follow-up of 28 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 human tumor colony forming assay (HTCFA) has been completed. Thirty-two patients have been studied at 6 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 nonsmall cell and small cell.lung cancer lines at 25-165 microgram/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.