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 language | English (US) |
|---|---|
| Pages (from-to) | 4771-4776 |
| Number of pages | 6 |
| Journal | Journal of Clinical Oncology |
| Volume | 26 |
| Issue number | 29 |
| DOIs | |
| State | Published - Oct 10 2008 |
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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 journal › Article
}
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 -