90YCC49 MONOCLONAL ANTIBODY IN ADVANCED NONSMALL CELL LUNG CANCER

该方案旨在确定90Y-CC49单抗联合α-干扰素治疗晚期非小细胞肺癌患者的最大耐受量。所有患者都将被组织诊断为转移性或无法切除的非小细胞肺癌。肿瘤标本将用肿瘤块免疫过氧化物酶染色检测TAG-72。TAG-72免疫反应阳性至少10%的患者将被考虑参加这项研究。在确定最大耐受剂量(MTD)之前，患者将按每个剂量水平至少三人一组的方式进入研究。研究前的评估将在临床上进行，并将指导患者在家中自我给予干扰素治疗。之后，病人将在GCRC接受为期3天的抗体治疗。将监测患者的不良反应、抗肿瘤效果、药代动力学、成像、剂量测定和免疫反应。90Y-CC49-PA-DOTA静脉注射的起始量为8mCI/m2，抗体剂量为CC49 10 mg，第1天静脉滴注30分钟以上。在此治疗之前，将使用100 5g试验剂量的冷(未标记)CC49和111In-CC49-Pd-DOTA(5mCi)10分钟输注。随后的剂量升级将以每个剂量水平的2.0mci/m2为基础，适用于不同的患者组，直到达到MTD。每个剂量级别的毒性数据将在进入下一个剂量级别之前提交给NCI进行审查。当达到MTD剂量时，另一组5例患者将按相同剂量水平的90Y-CC49用EDTA二钠钙治疗。从90Y-CC49输注前30分钟开始，每公斤患者体重25毫克EDTA钙钠在500毫升0.9%生理盐水中连续静脉输注6个12小时。如果EDTA联合给药导致骨髓抑制低于MTD指南，则EDTA 90Y-CC49将继续以2.0mci/m2的增量递增剂量，直到建立新的MTD。

This protocol is designed to determine the maximum tolerated dose (MTD) of 90Y-CC49 monoclonal antibody with alpha-interferon (IFN) in patients with advanced non-small cell lung cancer. All patients will have tissue diagnosis of metastatic or unresectable non-small cell lung carcinoma. Tumor specimens will be tested for TAG-72 using immunoperoxidase staining of tumor block. Patients with at least 10% positivity for immunoreactivity with TAG-72 will be considered for this study. The patients will be entered into the study in sets of at least three patients per dose level until the maximal tolerated dose (MTD) is identified. The pre-study evaluation will be done in the clinic, and patients will be instructed to self-administer interferon therapy at home. Thereafter, patients will be admitted for three days in the GCRC for antibody therapy. Patients will be monitored for adverse reactions, for antitumor effects, pharmacokinetics, imaging, dosimetry, and immune response. The initial dose of intravenous 90Y-CC49-PA-DOTA will be 8 mCi/m2 in an antibody dose of 10 mg ofCC49, infused over 30 minutes on day one. This therapy will be preceeded by 100 5g test dose of cold (unlabeled) CC49 and a 10 minutes infusion of 111IN-CC49-PD-DOTA(5mCi). Subsequent dose escalation will be on the basis of 2.0 mCi/m2 per dose level with different groups of patients until the MTD is reached. Toxicity data from each dose level will be submitted to NCI for review prior to proceeding to the next dose level. When the MTD dose is reached, a different group of 5 patients will be treated at the same dose level of 90Y-CC49 with calcium disodium EDTA. Six 12 hour continuous intravenous infusions of 25 mg calcium sodium EDTA per Kg of patient body weight in 500 ml 0.9% saline will be administered starting 30 minutes prior to the 90Y-CC49 infusion. If EDTA co-administration results in bone marrow suppression less than MTD guidelines, dose escalation at increments of 2.0 mCi/m2 90Y-CC49 will continue with EDTA until a new MTD is established.