title: A pilot safety trial investigating a vector-based vaccine targeting carcinoembryonic antigen in combination with radiotherapy in patients with gastrointestinal malignancies metastatic to the liver.
abstract: OBJECTIVE
  Previous studies have demonstrated the ability of non-lethal doses of radiation to alter the phenotype of tumor cells to facilitate immune mediated killing. This pilot study evaluated the tolerability of a vector-based vaccine targeting carcinoembryonic antigen (CEA) in combination with radiation therapy in patients with gastrointestinal malignancies metastatic to the liver.
  
  
  METHODS
  Patients enrolled had progressive CEA(+) tumors with metastatic liver lesions. Patients had received a median of three previous chemotherapy regimens, with a median of 2 months since their last chemotherapy regimen. Only 58% had metastatic disease limited to the liver. Vaccination commenced day 1 with biweekly boosters and split-course radiation (total 32 Gy) starting on day 21. Blood was collected at baseline and day 91 for immunological analysis.
  
  
  CONCLUSIONS
  A total of 12 patients were enrolled. There were no grade 3 or greater toxicities or grade 2 or greater hepatic toxicities. Median time on-study was 3 months, with the longest time on treatment being 5 months (n = 2). Immunological analysis was limited to two patients; neither showed an increase above baseline in CEA-specific T cells post-therapy. CEA/TRICOM vaccination in combination with low-dose radiation therapy is safe. There was limited evidence of activity in this patient population.
authors.affiliation: National Cancer Institute, National Institutes of Health, Center for Cancer Research, Laboratory of Tumor Immunology and Biology, 10 Center Dr, 8B09 MSC 1750, Bethesda, MD 20892, USA. gulleyj@mail.nih.gov
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.forename: Ravi A
authors.initials: RA
authors.lastname: Madan
authors.forename: Kwong-Yok
authors.initials: KY
authors.lastname: Tsang
authors.forename: Philip M
authors.initials: PM
authors.lastname: Arlen
authors.forename: Kevin
authors.initials: K
authors.lastname: Camphausen
authors.forename: Mahsa
authors.initials: M
authors.lastname: Mohebtash
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kamrava
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: Deborah
authors.initials: D
authors.lastname: Citrin
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D005587:Fowlpox virus / Q000235:genetics*; D005822:Genetic Vectors; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D054547:National Cancer Institute (U.S.); D010865:Pilot Projects; D011829:Radiation Dosage; D018714:Radiotherapy, Adjuvant; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014614:Vaccines, Synthetic / Q000627:therapeutic use
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D014614:Vaccines, Synthetic