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Cancer Chemother Pharmacol. 2014 Jan;73(1):151-61. doi: 10.1007/s00280-013-2333-4. Epub 2013 Nov 13.

Circulating proteins as potential biomarkers of sunitinib and interferon-α efficacy in treatment-naïve patients with metastatic renal cell carcinoma.

Author information

1
Pfizer Oncology, 10646 Science Center Drive, La Jolla, San Diego, CA, 92121, USA.

Abstract

PURPOSE:

We investigated potential biomarkers of efficacy in a phase III trial of sunitinib versus interferon-alpha (IFN-α), first-line in metastatic renal cell carcinoma (mRCC), by analyzing plasma levels of vascular endothelial growth factor (VEGF)-A, VEGF-C, soluble VEGF receptor-3 (sVEGFR-3) and interleukin (IL)-8.

METHODS:

Seven hundred and fifty mRCC patients were randomized to oral sunitinib 50 mg/day in repeated cycles of a 4-week on/2-week off schedule or IFN-α 9 million units subcutaneously thrice weekly. Plasma samples collected from a subset of 63 patients on days 1 and 28 of cycles 1-4 and at end of treatment were analyzed by ELISA.

RESULTS:

Baseline characteristics of biomarker-evaluated patients in sunitinib (N = 33) and IFN-α (N = 30) arms were comparable to their respective intent-to-treat populations. By univariate Cox regression analysis, low baseline soluble protein levels were associated with lower risk of progression/death (all P < 0.05): in both treatment arms, baseline VEGF-A and IL-8 were associated with overall survival (OS) and baseline VEGF-C with progression-free survival (PFS); in the sunitinib arm, baseline VEGF-A was associated with PFS and baseline sVEGFR-3 with PFS and OS; in the IFN-α arm, baseline IL-8 was associated with PFS. In multivariate analysis, baseline sVEGFR-3 and IL-8 remained independent predictors of OS in the sunitinib arm, while no independent predictors of outcome remained in the IFN-α arm. Pharmacodynamic changes were not associated with PFS or OS for any plasma protein investigated.

CONCLUSIONS:

Our findings suggest that, in mRCC, baseline VEGF-A and IL-8 may have prognostic value, while baseline sVEGFR-3 may predict sunitinib efficacy.

PMID:
24220935
PMCID:
PMC3889677
DOI:
10.1007/s00280-013-2333-4
[Indexed for MEDLINE]
Free PMC Article

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