9 AC COLLOIDAL DISPERSION INFUSION IN ADVANCED NON SMALL CELL LUNG CA

9 高级非小细胞肺 CA 中的 AC 胶体分散输注

• 批准号: 6264413
• 负责人: NATHAN LEVITAN
• 金额: $ 1.92万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6264413
• 关键词: DNA topoisomerases; antineoplastics; clinical research; drug screening /evaluation; human subject; human therapy evaluation; intravenous administration; neoplasm /cancer chemotherapy; pharmacokinetics; small cell lung cancer

Chemotherapy regimens which utilize conventional drugs for the treatment of non-small cell lung cancer can achieve response rates in the range of 20-40%. Despite these promising response rates, phase III studies which compare best supportive care to chemotherapy in non-small cell lung cancer have shown a maximum prolongation of survival of only 16 weeks. In this setting, the need to develop new, more effective first-line chemotherapy regimens for non-small cell lung cancer is clear. Studies performed in patients with small cell lung cancer and leukemia have demonstrated that patients' likelihood of responding to conventional chemotherapy regimens is not impaired by initial treatment with an investigational agent. Accordingly, this trial has been developed as first line therapy for patients with advanced non-small cell lung cancer. Patients who enroll in this trial and subsequently receive second line chemotherapy will be followed to determine their rate of response to such treatment. The objectives of this trial are to: 1)To determine if 9-aminocamptothecin colloidal dispersion administered as a 120 hour weekly infusion is an effective agent of treatment of advanced non-small cell lung cancer. 2)To observe the toxicity associated with this regimen among patients with advanced nonsmall cell lung cancer. 3) To measure the levels of topoisomerase I in tumor biopsy specimens obtained from patients with non small cell lung cancer entered on this trial. 4) To determine the 9-AC pharmacokinetics parameters and to correlate serum levels with toxicity and response to treatment. 5) To determine the mutagenic potential of 9-AC administered as a 120hr weekly infusion. Patients will receive a 5 day continuous intravenous chemotherapy treatment. After a 2 day rest, 9-AC will be repeated for a total of 3 weeks followed by a one week rest period. The 9-AC treatment will be repeated for as long as the tumor continues to shrink or remains stable, unless limiting side effects occur. Blood samples will be drawn prior to and following each treatment. The pharmacokinetic studies will be conducted on the GCRC.

使用常规药物治疗非小细胞肺癌的化疗方案可以达到20- 40%的反应率。 尽管有这些有希望的反应率，III期研究比较了最佳支持治疗与非小细胞肺癌化疗的最大延长生存期仅为16周。 在这种情况下，需要开发新的，更有效的非小细胞肺癌一线化疗方案是明确的。 在小细胞肺癌和白血病患者中进行的研究表明，患者对常规化疗方案的反应可能性不会因研究药物的初始治疗而受损。因此，该试验已被开发为晚期非小细胞肺癌患者的一线治疗。 将对入组本试验并随后接受二线化疗的患者进行随访，以确定其对此类治疗的应答率。本试验的目的是：1）确定9-氨基喜树碱胶体分散体每周输注120小时是否是治疗晚期非小细胞肺癌的有效药物。 2）观察该方案治疗晚期非小细胞肺癌的毒副反应。 3)目的检测非小细胞肺癌患者肿瘤活检标本中拓扑异构酶I的水平。 4)确定9-AC药代动力学参数，并将血清水平与毒性和治疗反应相关联。 5)确定9-AC每周输注120小时的致突变潜力。患者将接受为期5天的连续静脉化疗治疗。 停药2天后，9-AC将重复给药共3周，然后停药1周。 只要肿瘤继续缩小或保持稳定，9-AC治疗将重复进行，除非发生有限的副作用。 将在每次治疗前后采集血样。 将对GCRC进行药代动力学研究。