title: Potential applications for circulating tumor cells expressing the insulin-like growth factor-I receptor.
abstract: OBJECTIVE
  To detect insulin-like growth factor-IR (IGF-IR) on circulating tumor cells (CTC) as a biomarker in the clinical development of a monoclonal human antibody, CP-751,871, targeting IGF-IR.
  
  
  METHODS
  An automated sample preparation and analysis system for enumerating CTCs (CellTracks) was adapted for detecting IGF-IR-positive CTCs with a diagnostic antibody targeting a different IGF-IR epitope to CP-751,871. This assay was used in three phase I trials of CP-751,871 as a single agent or with chemotherapy and was validated using cell lines and blood samples from healthy volunteers and patients with metastatic carcinoma.
  
  
  RESULTS
  There was no interference between the analytic and therapeutic antibodies. Eighty patients were enrolled on phase I studies of CP-751,871, with 47 (59%) patients having CTCs detected during the study. Before treatment, 26 patients (33%) had CTCs, with 23 having detectable IGF-IR-positive CTCs. CP-751,871 alone, and CP-751,871 with cytotoxic chemotherapy, decreased CTCs and IGF-IR-positive CTCs; these increased toward the end of the 21-day cycle in some patients, falling again with retreatment. CTCs were commonest in advanced hormone refractory prostate cancer (11 of 20). Detectable IGF-IR expression on CTCs before treatment with CP-751,871 and docetaxel was associated with a higher frequency of prostate-specific antigen decline by >50% (6 of 10 versus 2 of 8 patients). A relationship was observed between sustained decreases in CTC counts and prostate-specific antigen declines by >50%.
  
  
  CONCLUSIONS
  IGF-IR expression is detectable by immunofluorescence on CTCs. These data support the further evaluation of CTCs in pharmacodynamic studies and patient selection, particularly in advanced prostate cancer.
authors.affiliation: Royal Marsden NHS Foundation Trust, London, United Kingdom. johann.de-bono@icr.ac.uk
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
authors.forename: Alex
authors.initials: A
authors.lastname: Adjei
authors.forename: Michael N
authors.initials: MN
authors.lastname: Pollak
authors.forename: Peter C
authors.initials: PC
authors.lastname: Fong
authors.forename: Paul
authors.initials: P
authors.lastname: Haluska
authors.forename: Luisa
authors.initials: L
authors.lastname: Roberts
authors.forename: Carrie
authors.initials: C
authors.lastname: Melvin
authors.forename: Madeline
authors.initials: M
authors.lastname: Repollet
authors.forename: David
authors.initials: D
authors.lastname: Chianese
authors.forename: Mark
authors.initials: M
authors.lastname: Connely
authors.forename: Leon W M M
authors.initials: LW
authors.lastname: Terstappen
authors.forename: Antonio
authors.initials: A
authors.lastname: Gualberto
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D005455:Fluorescent Antibody Technique; D006801:Humans; D007158:Immunologic Techniques; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D017526:Receptor, IGF Type 1