Phase 1 radioimmunotherapy study with lutetium 177-labeled anti-carbonic anhydrase IX monoclonal antibody girentuximab in patients with advanced renal cell carcinoma.

Abstract

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 ((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.

INTERVENTION:

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.

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/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.

CONCLUSIONS:

(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.

• Authors: Alexander B Stillebroer, Otto C Boerman, Ingrid M E Desar, Marije J Boers-Sonderen, Carla M L van Herpen, Johannes F Langenhuijsen, Peter M Smith-Jones, Egbert Oosterwijk, Wim J G Oyen, Peter F A Mulders
• Journal: European urology (Eur Urol) Vol. 64 Issue 3 Pg. 478-85 (Sep 2013) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 22980441 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antigens, Neoplasm
• G250 monoclonal antibody
• Immunoconjugates
• Radiopharmaceuticals
• Lutetium
• CA9 protein, human
• Carbonic Anhydrase IX
• Carbonic Anhydrases

Topics

• Adult
• Aged
• Antibodies, Monoclonal (adverse effects, metabolism, therapeutic use)
• Antigens, Neoplasm (immunology)
• Carbonic Anhydrase IX
• Carbonic Anhydrases (immunology)
• Carcinoma, Renal Cell (diagnostic imaging, enzymology, immunology, radiotherapy, secondary)
• Disease Progression
• Dose-Response Relationship, Radiation
• Female
• Humans
• Immunoconjugates (adverse effects, metabolism, therapeutic use)
• Kidney Neoplasms (diagnostic imaging, enzymology, immunology, pathology, radiotherapy)
• Lutetium (adverse effects, metabolism, therapeutic use)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Netherlands
• Radioimmunotherapy (adverse effects)
• Radionuclide Imaging
• Radiopharmaceuticals (adverse effects, metabolism, therapeutic use)
• Time Factors
• Tissue Distribution
• Treatment Outcome
• Tumor Burden
• Whole Body Imaging