RETRACTED: Pre-treatment levels of circulating free IGF-1 identify NSCLC patients who derive clinical benefit from figitumumab (Retracted article. See vol. 107, pg. 2024, 2012)

被引：69

作者：

Gualberto, A. ^{[1
,2
]}

Hixon, M. L. ^{[2
]}

Karp, D. D. ^{[3
]}

Li, D. ^{[1
]}

Green, S. ^{[1
]}

Dolled-Filhart, M. ^{[4
]}

Paz-Ares, L. G. ^{[5
]}

Novello, S. ^{[6
]}

Blakely, J. ^{[7
]}

Langer, C. J. ^{[8
]}

Pollak, M. N. ^{[9
]}

机构：

[1] Pfizer Oncol, Dept Clin Dev & Med Affairs, New London, CT 06320 USA

[2] Brown Univ, Warren Alpert Med Sch, Dept Pathol & Lab Med, Providence, RI 02903 USA

[3] Univ Texas Houston, MD Anderson Canc Ctr, Dept Thorac Oncol, Houston, TX 77030 USA

[4] HistoRx Inc, New Haven, CT 06511 USA

[5] Virgen del Rocio Univ Hosp, Dept Med Oncol, Seville 41013, Spain

[6] Univ Turin, Dept Med Oncol, I-10043 Turin, Italy

[7] West Clin, Dept Med Oncol, Memphis, TN 38120 USA

[8] Univ Penn, Abramson Canc Ctr, Div Hematol Oncol, Philadelphia, PA 19104 USA

[9] McGill Univ, Dept Med Oncol, Montreal, PQ H3T 1E2, Canada

来源：

BRITISH JOURNAL OF CANCER | 2011年 / 104卷 / 01期

关键词：

IGF-IR; IGF-1; figitumumab; NSCLC; GROWTH-FACTOR-I; CELL LUNG-CANCER; ELDERLY POPULATION; BINDING PROTEIN-3; INSULIN; BIOACTIVITY; IGFBP-1; COMBINATION; CP-751,871; EXPRESSION;

D O I：

10.1038/sj.bjc.6605972

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 METHODS: 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, rho = -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 (rho = 0.594, P = 0.021) and inversely with E-cadherin (rho = -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. British Journal of Cancer (2011) 104, 68-74. doi:10.1038/sj.bjc.6605972 www.bjcancer.com Published online 23 November 2010 (C) 2011 Cancer Research UK

引用

页码：68 / 74

页数：7

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