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

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Abstract

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, progressionfree survival, and overall survival in chemotherapy-treated patients with advanced NSCLC.

Original languageEnglish (US)
Pages (from-to)4771-4776
Number of pages6
JournalJournal of Clinical Oncology
Volume26
Issue number29
DOIs
StatePublished - Oct 10 2008

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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