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

Research output: Contribution to journalArticle

76 Citations (Scopus)

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

Fingerprint

Osteopontin
Platinum
Non-Small Cell Lung Carcinoma
Drug Therapy
tirapazamine
Survival
Plasminogen Activator Inhibitor 1
Vascular Endothelial Growth Factor A
Neoplasms
Carboplatin
Cytotoxins
Paclitaxel
Disease-Free Survival
Therapeutics
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lower osteopontin plasma levels are associated with superior outcomes in advanced non-small-cell lung cancer patients receiving platinum-based chemotherapy : SWOG study S0003. / Mack, Philip; Redman, Mary W.; Chansky, Kari; Williamson, Stephen K.; Farneth, Nichole C.; Lara, Primo N; Franklin, Wilbur A.; Le, Quynh Thu; Crowley, John J.; Gandara, David R.

In: Journal of Clinical Oncology, Vol. 26, No. 29, 10.10.2008, p. 4771-4776.

Research output: Contribution to journalArticle

Mack, Philip ; Redman, Mary W. ; Chansky, Kari ; Williamson, Stephen K. ; Farneth, Nichole C. ; Lara, Primo N ; Franklin, Wilbur A. ; Le, Quynh Thu ; Crowley, John J. ; Gandara, David R. / Lower osteopontin plasma levels are associated with superior outcomes in advanced non-small-cell lung cancer patients receiving platinum-based chemotherapy : SWOG study S0003. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 29. pp. 4771-4776.
@article{0b83bacd31fa4c80950c3fd5d01d31b1,
title = "Lower osteopontin plasma levels are associated with superior outcomes in advanced non-small-cell lung cancer patients receiving platinum-based chemotherapy: SWOG study S0003",
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.",
author = "Philip Mack and Redman, {Mary W.} and Kari Chansky and Williamson, {Stephen K.} and Farneth, {Nichole C.} and Lara, {Primo N} and Franklin, {Wilbur A.} and Le, {Quynh Thu} and Crowley, {John J.} and Gandara, {David R}",
year = "2008",
month = "10",
day = "10",
doi = "10.1200/JCO.2008.17.0662",
language = "English (US)",
volume = "26",
pages = "4771--4776",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "29",

}

TY - JOUR

T1 - Lower osteopontin plasma levels are associated with superior outcomes in advanced non-small-cell lung cancer patients receiving platinum-based chemotherapy

T2 - SWOG study S0003

AU - Mack, Philip

AU - Redman, Mary W.

AU - Chansky, Kari

AU - Williamson, Stephen K.

AU - Farneth, Nichole C.

AU - Lara, Primo N

AU - Franklin, Wilbur A.

AU - Le, Quynh Thu

AU - Crowley, John J.

AU - Gandara, David R

PY - 2008/10/10

Y1 - 2008/10/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=54249152439&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54249152439&partnerID=8YFLogxK

U2 - 10.1200/JCO.2008.17.0662

DO - 10.1200/JCO.2008.17.0662

M3 - Article

C2 - 18779603

AN - SCOPUS:54249152439

VL - 26

SP - 4771

EP - 4776

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 29

ER -