title: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Determination of the MTD was the primary and therapeutic efficacy was the secondary outcome measurement of the study.
  
  
  CONCLUSIONS
  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.affiliation: Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. alexanderstillebroer@hotmail.com
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Stillebroer
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
authors.forename: Ingrid M E
authors.initials: IM
authors.lastname: Desar
authors.forename: Marije J
authors.initials: MJ
authors.lastname: Boers-Sonderen
authors.forename: Carla M L
authors.initials: CM
authors.lastname: van Herpen
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Langenhuijsen
authors.forename: Peter M
authors.initials: PM
authors.lastname: Smith-Jones
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
authors.forename: Peter F A
authors.initials: PF
authors.lastname: Mulders
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000201:enzymology / Q000276:immunology / Q000532:radiotherapy* / Q000556:secondary; D018450:Disease Progression; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D008187:Lutetium / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009426:Netherlands; D016499:Radioimmunotherapy / Q000009:adverse effects; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D013997:Time Factors; D014018:Tissue Distribution; D016896:Treatment Outcome; D047368:Tumor Burden; D051598:Whole Body Imaging
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C106533:G250 monoclonal antibody; D018796:Immunoconjugates; D019275:Radiopharmaceuticals; D008187:Lutetium; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases