Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Eur Urol. 2013 Sep;64(3):478-85. doi: 10.1016/j.eururo.2012.08.024. Epub 2012 Aug 21.
Patients with metastatic clear cell renal cell carcinoma (ccRCC) have a dismal prognosis. Therefore, new and less toxic treatments are needed.
We determined the maximum tolerated dose (MTD) and potential therapeutic efficacy of multiple infusions of lutetium 177 ((177)Lu)-girentuximab (cG250) on various dose levels in a phase 1 trial in patients with progressive metastasized ccRCC.
DESIGN, SETTING, AND PARTICIPANTS: In this uncontrolled case series in 23 patients with progressive ccRCC metastases, cG250 accumulation was verified by diagnostic indium 111-cG250 imaging. Patients then received a high-activity dose of (177)Lu-cG250.
Groups of three patients received (177)Lu-cG250, starting at a dose level of 1110 MBq/m(2)(177)Lu-cG250, with dose increments of 370 MBq/m(2) per group. In the absence of persistent toxicity, progressive disease, and accelerated blood clearance, patients were eligible for retreatment after 3 mo with 75% of the previous activity dose. Patients could receive a total of three treatment cycles.
Determination of the MTD was the primary and therapeutic efficacy was the secondary outcome measurement of the study.
The MTD was 2405 MBq/m(2) because higher doses resulted in dose-limiting myelotoxicity. Some patients received second (13 of 23 [56%]) and third (4 of 23 [17%]) treatment cycles. Most patients (17 of 23 [74%]) demonstrated stable disease 3 mo after the first treatment, and one patient showed a partial response that lasted for 9 mo. Mean growth of target tumor lesions was reduced from 40.4% (95% confidence interval [CI], ± 17.0) during the last 3 mo before study entry to 5.5% (95% CI, ± 5.3; p<0.001) at 3 mo after the first treatment cycle. No major nonhematologic side effects were observed.
(177)Lu-cG250 radioimmunotherapy in metastatic ccRCC patients is well tolerated at an activity dose level as high as 2405 MBq/m(2) (MTD). Radioimmunotherapy with (177)Lu-cG250 may stabilize previously progressive metastatic ccRCC.
转移性透明细胞肾细胞癌（ccRCC）患者预后极差。因此，需要新的、毒性更低的治疗方法。
我们在 23 例进展性转移性 ccRCC 患者中进行了一项 1 期试验，以确定不同剂量水平下多次输注镥 177（177Lu）-吉妥单抗（cG250）的最大耐受剂量（MTD）和潜在治疗效果。
设计、设置和参与者：在这项无对照的 23 例 ccRCC 转移进展患者的病例系列研究中，通过诊断性铟 111-cG250 成像验证 cG250 的蓄积。然后，患者接受高活性剂量的 177Lu-cG250。
3 组患者分别接受 1110 MBq/m2 177Lu-cG250 的起始剂量，每组递增 370 MBq/m2。如果没有持续毒性、疾病进展和加速血液清除，患者在 3 个月后有资格接受前一疗程 75%的活性剂量进行再治疗。患者可接受总共三个治疗周期。
确定 MTD 是研究的主要终点，治疗效果是次要终点。
MTD 为 2405 MBq/m2，因为更高的剂量会导致剂量限制的骨髓毒性。一些患者接受了第二（23 例中的 13 例[56%]）和第三（23 例中的 4 例[17%]）治疗周期。大多数患者（23 例中的 17 例[74%]）在首次治疗后 3 个月显示疾病稳定，1 例患者显示部分缓解，持续 9 个月。首次治疗周期后 3 个月，靶肿瘤病变的平均生长从研究入组前最后 3 个月的 40.4%（95%置信区间[CI]，±17.0）减少至 5.5%（95%CI，±5.3；p<0.001）。未观察到主要非血液学副作用。
（177）Lu-cG250 放射性免疫疗法在转移性 ccRCC 患者中耐受性良好，活性剂量高达 2405 MBq/m2（MTD）。（177）Lu-cG250 放射性免疫疗法可稳定先前进展的转移性 ccRCC。
