title: Phase 2 Study of Lutetium 177-Labeled Anti-Carbonic Anhydrase IX Monoclonal Antibody Girentuximab in Patients with Advanced Renal Cell Carcinoma.
abstract: Despite advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC), there is still an unmet need in the treatment of this disease. A phase 2 radioimmunotherapy (RIT) trial with lutetium 177 ((177)Lu)-girentuximab was initiated to evaluate the efficacy of this approach. In this nonrandomized single-arm trial, patients with progressive metastatic ccRCC who met the inclusion criteria received 2405 MBq/m(2) of (177)Lu-girentuximab intravenously. In the absence of persistent toxicity and progressive disease, patients were eligible for retreatment after 3 mo with 75% of the previous activity dose. A total of 14 patients were included. After the first therapeutic infusion, eight patients (57%) had stable disease (SD) and one (7%) had a partial regression. The treatment was generally well tolerated but resulted in grade 3-4 myelotoxicity in most patients. After the second cycle, continued SD was observed in five of six patients, but none were eligible for retreatment due to prolonged thrombocytopenia. In conclusion, RIT with (177)Lu-girentuximab resulted in disease stabilization in 9 of 14 patients with progressive metastatic ccRCC, but myelotoxicity prevented retreatment in some patients.
  
  
  
  We investigated the efficacy of lutetium 177-girentuximab radioimmunotherapy in patients with metastatic kidney cancer. The treatment resulted in disease stabilization in 9 of 14 patients. The main toxicity was prolonged low blood cell counts.
  
  
  
  ClinicalTrials.gov identifier: NCT02002312 (https://clinicaltrials.gov/ct2/show/NCT02002312).
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: stijn.muselaers@radboudumc.nl.
authors.forename: Constantijn H J
authors.initials: CH
authors.lastname: Muselaers
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marye J
authors.initials: MJ
authors.lastname: Boers-Sonderen
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: van Oostenbrugge
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ingrid M E
authors.initials: IM
authors.lastname: Desar
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Stillebroer
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Sasja F
authors.initials: SF
authors.lastname: Mulder
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Carla M L
authors.initials: CM
authors.lastname: van Herpen
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Johan F
authors.initials: JF
authors.lastname: Langenhuijsen
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Peter F A
authors.initials: PF
authors.lastname: Mulders
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects / Q000627:therapeutic use*; D000071231:Carbonic Anhydrase IX / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000532:radiotherapy* / Q000556:secondary; D018572:Disease-Free Survival; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008187:Lutetium / Q000009:adverse effects / Q000627:therapeutic use*; D009503:Neutropenia / Q000139:chemically induced; D065228:Non-Randomized Controlled Trials as Topic; D016499:Radioimmunotherapy / Q000009:adverse effects; D011868:Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*; D019233:Retreatment; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000911:Antibodies, Monoclonal; D000074322:Antineoplastic Agents, Immunological; C106533:G250 monoclonal antibody; D011868:Radioisotopes; D008187:Lutetium; C000615061:Lutetium-177; D000071231:Carbonic Anhydrase IX
keywords: CAIX; Clear cell renal cell carcinoma; Girentuximab; Radioimmunotherapy