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RETRACTED ARTICLE

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Br J Cancer. 2011 Jan 4;104(1):68-74. doi: 10.1038/sj.bjc.6605972. Epub 2010 Nov 23.

Pre-treatment levels of circulating free IGF-1 identify NSCLC patients who derive clinical benefit from figitumumab.

Author information

1
The Department of Clinical Development and Medical Affairs, Pfizer Oncology, New London, CT 06320, USA. antonio.gualberto@mpi.com

Abstract

BACKGROUND:

Phase III trials of the anti-insulin-like growth factor type 1 receptor (IGF-IR) antibody figitumumab (F) in unselected non-small-cell lung cancer (NSCLC) patients were recently discontinued owing to futility. Here, we investigated a role of free IGF-1 (fIGF-1) as a potential predictive biomarker of clinical benefit from F treatment.

MATERIALS AND METHOD:

Pre-treatment circulating levels of fIGF-1 were tested in 110 advanced NSCLC patients enrolled in a phase II study of paclitaxel and carboplatin given alone (PC) or in combination with F at doses of 10 or 20 mg kg(-1) (PCF10, PCF20).

RESULTS:

Cox proportional hazards model interactions were between 2.5 and 3.5 for fIGF-1 criteria in the 0.5-0.9 ng ml(-1) range. Patients above each criterion had a substantial improvement in progression-free survival on PCF20 related to PC alone. Free IGF-1 correlated inversely with IGF binding protein 1 (IGFBP-1, ρ=-0.295, P=0.005), and the pre-treatment ratio of insulin to IGFBP-1 was also predictive of F clinical benefit. In addition, fIGF-1 levels correlated with tumour vimentin expression (ρ=0.594, P=0.021) and inversely with E-cadherin (ρ=-0.389, P=0.152), suggesting a role for fIGF-1 in tumour de-differentiation.

CONCLUSION:

Free IGF-1 may contribute to the identification of a subset of NSCLC patients who benefit from F therapy.

PMID:
21102589
PMCID:
PMC3039819
DOI:
10.1038/sj.bjc.6605972
[Indexed for MEDLINE]
Free PMC Article

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