Skip to main content
release_alert
Welcome to the new Scholars 3.0! Read about new features and let us know what you think.
cancel

Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor.

Publication ,  Journal Article
Norden-Zfoni, A; Desai, J; Manola, J; Beaudry, P; Force, J; Maki, R; Folkman, J; Bello, C; Baum, C; DePrimo, SE; Shalinsky, DR; Demetri, GD ...
Published in: Clin Cancer Res
May 1, 2007

PURPOSE: There is an unmet need for noninvasive markers to measure the biological effects of targeted agents, particularly those inhibiting the vascular endothelial growth factor (VEGF) receptor (VEGFR) pathway, and identify patients most likely to benefit from treatment. In this study, we investigated potential blood-based biomarkers for SU11248 (sunitinib malate), a multitargeted tyrosine kinase inhibitor, in patients with metastatic imatinib-refractory gastrointestinal stromal tumors. EXPERIMENTAL DESIGN: Patients (n=73) enrolled in a phase I/II trial received SU11248 daily for 14 or 28 days followed by 14 days without treatment per cycle. Clinical benefit was defined as progression-free survival of >6 months. We assessed plasma markers, including VEGF and soluble VEGFR-2 (sVEGFR-2), and two cellular populations bearing VEGF receptors: monocytes and, in a subset of patients, mature circulating endothelial cells (CEC). RESULTS: Compared to patients with progressive disease, patients with clinical benefit had significantly greater increases in CECs (0.52 versus -0.01 CEC/microL/d, P=0.03) and smaller decreases in monocyte levels (47% versus 60%, P=0.007) during cycle 1. VEGF increased by 2.2-fold and sVEGFR-2 decreased 25% during the first 2 weeks of treatment. Neither plasma marker correlated with clinical outcome although a modest inverse correlation was observed between sVEGFR-2 changes and plasma drug levels. Monocytes, VEGF, and sVEGFR-2 all rebounded towards baseline off treatment. CONCLUSIONS: Monocytes, VEGF, and sVEGFR-2 were consistently modulated by treatment, suggesting that they may serve as pharmacodynamic markers for SU11248. Changes in CECs and monocytes, but not the plasma markers, differed between the patients with clinical benefit and those with progressive disease. These end points merit further investigation in future trials to determine their utility as markers of SU11248 activity and clinical benefit in gastrointestinal stromal tumors and other tumor types.

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

May 1, 2007

Volume

13

Issue

9

Start / End Page

2643 / 2650

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor Receptor-2
  • Vascular Endothelial Growth Factor A
  • Treatment Outcome
  • Sunitinib
  • Pyrroles
  • Pyrimidines
  • Piperazines
  • Oncology & Carcinogenesis
  • Monocytes
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Norden-Zfoni, A., Desai, J., Manola, J., Beaudry, P., Force, J., Maki, R., … Heymach, J. V. (2007). Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor. Clin Cancer Res, 13(9), 2643–2650. https://doi.org/10.1158/1078-0432.CCR-06-0919
Norden-Zfoni, Anat, Jayesh Desai, Judith Manola, Paul Beaudry, Jeremy Force, Robert Maki, Judah Folkman, et al. “Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor.Clin Cancer Res 13, no. 9 (May 1, 2007): 2643–50. https://doi.org/10.1158/1078-0432.CCR-06-0919.
Norden-Zfoni A, Desai J, Manola J, Beaudry P, Force J, Maki R, et al. Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor. Clin Cancer Res. 2007 May 1;13(9):2643–50.
Norden-Zfoni, Anat, et al. “Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor.Clin Cancer Res, vol. 13, no. 9, May 2007, pp. 2643–50. Pubmed, doi:10.1158/1078-0432.CCR-06-0919.
Norden-Zfoni A, Desai J, Manola J, Beaudry P, Force J, Maki R, Folkman J, Bello C, Baum C, DePrimo SE, Shalinsky DR, Demetri GD, Heymach JV. Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor. Clin Cancer Res. 2007 May 1;13(9):2643–2650.

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

May 1, 2007

Volume

13

Issue

9

Start / End Page

2643 / 2650

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor Receptor-2
  • Vascular Endothelial Growth Factor A
  • Treatment Outcome
  • Sunitinib
  • Pyrroles
  • Pyrimidines
  • Piperazines
  • Oncology & Carcinogenesis
  • Monocytes
  • Male