BACKGROUND: Patients with metastatic clear cell renal cell carcinoma (ccRCC) have a dismal prognosis.
Therefore, new and less toxic treatments are needed.
OBJECTIVE: We determined the maximum tolerated dose (MTD) and potential therapeutic efficacy of multiple infusions of lutetium 177 (177Lu)-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 177Lu-cG250.
INTERVENTION: Groups of three patients received 177Lu-cG250, starting at a dose level of 1110 MBq/m2177Lu-cG250, with dose increments of 370 MBq/m2 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.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Determination of the MTD was the primary and therapeutic efficacy was the secondary outcome measurement of the study.
RESULTS AND LIMITATIONS: The MTD was 2405 MBq/m2 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.
CONCLUSIONS: 177Lu-cG250 radioimmunotherapy in metastatic ccRCC patients is well tolerated at an activity dose level as high as 2405 MBq/m2 (MTD). Radioimmunotherapy with 177Lu-cG250 may stabilize previously progressive metastatic ccRCC.
Written by:
Stillebroer AB, Boerman OC, Desar IM, Boers-Sonderen MJ, van Herpen CM, Langenhuijsen JF, Smith-Jones PM, Oosterwijk E, Oyen WJ, Mulders PF. Are you the author?
Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Reference: Eur Urol. 2012 Aug 21. pii: S0302-2838(12)00959-1.
doi: 10.1016/j.eururo.2012.08.024
PubMed Abstract
PMID: 22980441
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