title: Repeated adjuvant anti-CEA radioimmunotherapy after resection of colorectal liver metastases: Safety, feasibility, and long-term efficacy results of a prospective phase 2 study.
abstract: BACKGROUND
  In previous work, a single administration of anticarcinoembryonic antigen (anti-CEA)131I-labetuzumab radioimmunotherapy (RIT) after complete resection of colorectal liver metastases was well tolerated and significantly improved survival compared with controls. In the current phase 2 trial, the authors studied repeated RIT in the same setting, examining safety, feasibility, and efficacy.
  
  
  METHODS
  Sixty-three patients (median age, 64.5 years) received RIT at 40 to 50 millicuries/m2per dose. Before the receipt of RIT, restaging was performed with computed tomography/magnetic resonance imaging and18F-fluorodeoxyglucose-positron emission to confirm that patients were "truly adjuvant." Patients who had elevated serum CEA levels or radiographically inconclusive new lesions were classified as "possibly nonadjuvant," but they also received RIT. Time to progression (TTP), overall survival (OS), and cause-specific survival (CSS) were calculated. The median follow-up was 54 months.
  
  
  RESULTS
  After the first course of RIT, 14 of 63 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity; 19 patients did not receive the second course of RIT because of impaired performance status (N = 5) or relapse (N = 14). After the second course of RIT, 9 of 44 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity. Five patients developed myelodysplastic syndrome (MDS) from 22 to 55 months after their last RIT. The median TTP, OS, and CSS for all patients were 16, 55, and 60 months, respectively. The "truly adjuvant" patients (N = 39) had an improved median TTP (not reached vs 6.1 months; hazard ratio, 0.12; P < .001), OS (75.6 vs 33.4 months; hazard ratio, 0.44; P = .014), and CSS (not reached vs 41.4 months; hazard ratio,0.42; P = .014) compared with "possibly nonadjuvant" patients (N = 24).
  
  
  CONCLUSIONS
  Repeated RIT with131I-labetuzumab is feasible but is associated with hematotoxicity. Survival is very encouraging, especially for "truly adjuvant" patients. However, the maximum safe dose of131I-labetuzumab is a single administration of 50 millicuries/m2. Cancer 2017;123:638-649. © 2016 American Cancer Society.
authors.affiliation: Department of Nuclear Medicine, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Carsten-O
authors.initials: CO
authors.lastname: Sahlmann
authors.affiliation: Department of General, Visceral, and Pediatric Surgery, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Kia
authors.initials: K
authors.lastname: Homayounfar
authors.affiliation: Department of General, Visceral, and Pediatric Surgery, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Niessner
authors.affiliation: Department of Medical Statistics, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Dyczkowski
authors.affiliation: Department of General, Visceral, and Pediatric Surgery, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Lena-Christin
authors.initials: LC
authors.lastname: Conradi
authors.affiliation: Department of Hematology and Medical Oncology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Braulke
authors.affiliation: Department of Nuclear Medicine, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Meller
authors.affiliation: Department of Medical Statistics, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Beißbarth
authors.affiliation: Department of General, Visceral, and Pediatric Surgery, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: B Michael
authors.initials: BM
authors.lastname: Ghadimi
authors.affiliation: Department of Nuclear Medicine, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Meller
authors.affiliation: Center for Molecular Medicine and Immunology, Garden State Cancer Center, Morris Plains, New Jersey.|Immunomedics, Inc, Morris Plains, New Jersey.
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.affiliation: Department of General, Visceral, and Pediatric Surgery, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Liersch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects*; D002272:Carcinoembryonic Antigen / Q000276:immunology* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000532:radiotherapy / Q000601:surgery; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016499:Radioimmunotherapy / Q000009:adverse effects*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes; C110010:labetuzumab
keywords: adjuvant therapy; carcinoembryonic antigen; colorectal liver metastases; labetuzumab; radioimmunotherapy