Lack of efficacy of two consecutive treatments of radioimmunotherapy with 131I-cG250 in patients with metastasized clear cell renal cell carcinoma
Lack of efficacy of two consecutive treatments of radioimmunotherapy with 131I-cG250 in patients with metastasized clear cell renal cell carcinoma
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DOI：
10.1200/jco.2005.07.732
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发表时间：
2005-09-20
影响因子：
45.3
通讯作者：
Oyen, WJG
中科院分区：
文献类型：
--
作者：
Brouwers, AH;Mulders, PFA;Oyen, WJG
目的：以前的一项使用I-131标记的嵌合单克隆抗体cG 250在进行性转移性肾细胞癌（RCC）患者中进行的活性剂量递增研究导致偶尔的治疗反应。本研究旨在确定两种I-131-cG 250序贯高剂量治疗的安全性和疗效。患者和方法29例进行性转移性肾细胞癌患者接受低剂量I-131-cG 250治疗，以评估优先靶向转移病灶，1周后用2220 MBq/m2 I-131-cG 250（n = 27）首次放射免疫治疗（RIT）。如果未观察到4级血液学毒性，则在3个月后给予第二次低剂量I-131-cG 250（n = 20）。当血液清除未加速时，以1110 MBq/m2（n = 3）或1665 MBq/m2（n = 16）的活性剂量给予I-131-cG 250的第二次RIT。结果第二次RIT的最大耐受剂量（MTD）为1，665 MBq/m2，因为其血液学毒性是剂量限制性的。基于意向治疗分析，在两次RIT治疗后，29例患者中有5例病情稳定，而29例患者中有14例病情仍在进展。2例患者没有接受RIT，和8的29只接受了一个I-131-cG 250 RIT，因为4级血液毒性，形成人抗嵌合抗体，或disease progression.Conclusion在进行性终末期肾癌患者中，第二次治疗的MTD是第一次RIT的MTD的75%。在大多数患者中，两个周期的I-131-Cl可以安全地给药，没有严重的毒性。未观察到客观反应，但偶尔两次RIT剂量可使先前进行性疾病稳定。
Purpose A previous activity dose-escalation study using I-131-labeled chimeric monoclonal antibody cG250 in patients with progressive metastatic renal cell carcinoma (RCC) resulted in occasional therapeutic responses. The present study was designed to determine the safety and therapeutic efficacy of two sequential high-dose treatments with I-131-cG250.Patients and Methods Patients (n = 29) with progressive metastatic RCC received a low dose of I-131-cG250 for assessment of preferential targeting of metastatic lesions, followed by the first radioimmunotherapy (RIT) with 2220 MBq/m(2) I-131-cG250 (n = 27) 1 week later. If no grade 4 hematologic toxicity was observed, a second low-dose I-131-cG250 (n = 20) was given 3 months later. When blood clearance was not accelerated, a second RIT of I-131-cG250 was administered at an activity-dose of 1110 MBq/m(2) (n = 3) or 1665 MBq/m(2) (n = 16). Patients were monitored weekly for toxicity, and tumor size was evaluated by computed tomography once every 3 months intervals.Results The maximum-tolerated dose (MTD) of the second RIT was 1,665 MBq/m(2) because of dose-limiting hematological toxicity. Based on an intention-to-treat analysis, after two RIT treatments, the disease stabilized in five of 29 patients, whereas it remained progressive in 14 of 29 patients. Two patients received no RIT, and eight of 29 received only one I-131-cG250 RIT because of grade 4 hematologic toxicity, formation of human antichimeric antibodies, or disease progression.Conclusion In patients with progressive end-stage RCC, the MTD of the second treatment was 75% of the MTD of the first RIT. In the majority of patients, two cycles of I-131-cl could be safely administered without severe toxicity. No objective responses were observed, but occasionally two RIT doses resulted in stabilization of previously progressive disease.