PMID- 17575225
OWN - NLM
STAT- MEDLINE
DCOM- 20071004
LR  - 20220129
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 13
IP  - 12
DP  - 2007 Jun 15
TI  - Potential applications for circulating tumor cells expressing the insulin-like 
      growth factor-I receptor.
PG  - 3611-6
AB  - PURPOSE: 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. EXPERIMENTAL DESIGN: 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.
FAU - de Bono, Johann S
AU  - de Bono JS
AD  - Royal Marsden NHS Foundation Trust, London, United Kingdom. 
      johann.de-bono@icr.ac.uk
FAU - Attard, Gerhardt
AU  - Attard G
FAU - Adjei, Alex
AU  - Adjei A
FAU - Pollak, Michael N
AU  - Pollak MN
FAU - Fong, Peter C
AU  - Fong PC
FAU - Haluska, Paul
AU  - Haluska P
FAU - Roberts, Luisa
AU  - Roberts L
FAU - Melvin, Carrie
AU  - Melvin C
FAU - Repollet, Madeline
AU  - Repollet M
FAU - Chianese, David
AU  - Chianese D
FAU - Connely, Mark
AU  - Connely M
FAU - Terstappen, Leon W M M
AU  - Terstappen LW
FAU - Gualberto, Antonio
AU  - Gualberto A
LA  - eng
GR  - G0501019/MRC_/Medical Research Council/United Kingdom
PT  - Clinical Trial, Phase I
PT  - Journal Article
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antineoplastic Agents/therapeutic use
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - *Immunologic Techniques
MH  - Neoplasms/*drug therapy/metabolism
MH  - Neoplastic Cells, Circulating/*metabolism
MH  - Receptor, IGF Type 1/*metabolism
MH  - Treatment Outcome
EDAT- 2007/06/19 09:00
MHDA- 2007/10/05 09:00
CRDT- 2007/06/19 09:00
PHST- 2007/06/19 09:00 [pubmed]
PHST- 2007/10/05 09:00 [medline]
PHST- 2007/06/19 09:00 [entrez]
AID - 13/12/3611 [pii]
AID - 10.1158/1078-0432.CCR-07-0268 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2007 Jun 15;13(12):3611-6. doi: 10.1158/1078-0432.CCR-07-0268.