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

利用常规药物治疗非小细胞肺癌的化疗方案可达到20%-40%的有效率。尽管有这些有希望的应答率，但在非小细胞肺癌中比较最佳支持性治疗和化疗的第三阶段研究显示，最大限度地延长了16周的生存时间。在这种背景下，开发新的、更有效的非小细胞肺癌一线化疗方案的必要性是显而易见的。在小细胞肺癌和白血病患者中进行的研究表明，患者对传统化疗方案的反应不会因为研究药物的初始治疗而受到影响。因此，这项试验已被开发为晚期非小细胞肺癌患者的一线治疗方法。参加这项试验并随后接受二线化疗的患者将接受跟踪，以确定他们对这种治疗的应答率。这项试验的目的是：1)确定每周输注120小时的9-氨基喜树碱胶体分散体是否是治疗晚期非小细胞肺癌的有效药物。2)观察该方案对晚期非小细胞肺癌患者的毒副反应。3)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)测定9-AC的药代动力学参数，并将血药浓度与毒性和治疗反应相关联。5)测定每周输注120小时的9-AC的致突变潜能。患者将接受为期5天的持续静脉化疗。休息2天后，重复9-AC，共3周，然后休息1周。只要肿瘤继续缩小或保持稳定，9-AC治疗就会重复进行，除非出现有限的副作用。在每次治疗之前和之后都将抽取血样。药代动力学研究将在GCRC上进行。

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.