Originally published as JCO Early Release 10.1200/JCO.2008.17.0662 on September 8 2008

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Lower Osteopontin Plasma Levels Are Associated With Superior Outcomes in Advanced Non–Small-Cell Lung Cancer Patients Receiving Platinum-Based Chemotherapy: SWOG Study S0003

Philip C. Mack, Mary W. Redman, Kari Chansky, Stephen K. Williamson, Nichole C. Farneth, Primo N. Lara, Jr, Wilbur A. Franklin, Quynh-Thu Le, John J. Crowley, David R. Gandara

From the University of California, Davis Cancer Center, Sacramento; Stanford University, Stanford; Veterans Administration of Northern California, Martinez, CA; Fred Hutchinson Cancer Research Center; Cancer Research and Biostatistics, Southwest Oncology Group, Seattle, WA; University of Kansas Medical Center, Kansas City, KS; and University of Colorado Health Sciences Center, Denver, CO

Corresponding author: Philip C. Mack, PhD, Division of Hematology and Oncology, University of California, Davis Cancer Center, 4501 X St, Ste 3016, Sacramento, CA 95817; e-mail: pcmack{at}ucdavis.edu

Purpose S0003 was a phase III trial of carboplatin/paclitaxel with or without the hypoxic cytotoxin tirapazamine in patients with advanced or metastatic non–small-cell lung cancer (NSCLC). We investigated the relationship between clinical outcomes and plasma levels of the hypoxia-associated protein osteopontin (OPN) in patients on this protocol.

Patients and Methods Baseline plasma was obtained from 172 patients. In 56 patients, sequential plasma was obtained after one or two cycles. Concentrations of OPN, as well as plasminogen activator inhibitor-1 (PAI-1) and vascular endothelial growth factor (VEGF), were measured using enzyme-linked immunosorbent assay. Tumor expression of OPN was assessed by immunohistochemistry in 61 matched archival specimens.

Results Patients with lower OPN levels (below the median) had a significantly superior overall survival compared with patients with higher levels, regardless of treatment arm (hazard ratio [HR] = 0.60, P = .002). A similar correlation was observed for progression-free survival (HR = 0.69, P = .02). When examined as a continuous variable, OPN maintained its significant association with both progression-free (HR = 1.05, P = .01) and overall survival (HR = 1.09, P < .0001). Patients with lower plasma OPN levels were significantly more likely to have tumor response (P = .03). No differences were observed between treatment arms. Tumor OPN levels did not correlate with patient outcomes or with plasma levels. No associations were observed between patient outcomes and VEGF or PAI-1 levels; however, plasma concentrations of these markers were significantly interrelated (P < .0001) and significantly decreased after treatment (P = .0002 and P = .03, respectively).

Conclusion Pretreatment plasma levels of OPN are significantly associated with patient response, progression-free survival, and overall survival in chemotherapy-treated patients with advanced NSCLC.

published online ahead of print at www.jco.org on September 8, 2008

Supported by Grants No. R01-CA107228 (P.C.M.), R01 CA118582 (Q.-T.L.), and 5U10 CA32102 from the National Cancer Institute, and by The Hope Foundation.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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