Integrating cytokines and angiogenic factors and tumour bulk with selected clinical criteria improves determination of prognosis in advanced renal cell carcinoma.

Abstract

BACKGROUND:

In two clinical trials of the vascular endothelial growth factor (VEGF) receptor inhibitor pazopanib in advanced renal cell carcinoma (mRCC), we found interleukin-6 as predictive of pazopanib benefit. We evaluated the prognostic significance of candidate cytokines and angiogenic factors (CAFs) identified in that work relative to accepted clinical parameters.

METHODS:

Seven preselected plasma CAFs (interleukin-6, interleukin-8, osteopontin, VEGF, hepatocyte growth factor, tissue inhibitor of metalloproteinases (TIMP-1), and E-selectin) were measured using multiplex ELISA in plasma collected pretreatment from 343 mRCC patients participating in the phase 3 registration trial of pazopanib vs placebo (NCT00334282). Tumour burden (per sum of longest diameters (SLD)) and 10 other clinical factors were also analysed for association with overall survival (OS; based on initial treatment assignment).

RESULTS:

Osteopontin, interleukin-6, and TIMP-1 were independently associated with OS in multivariable analysis. A model combining the three CAFs and five clinical variables (including SLD) had higher prognostic accuracy than the International Metastatic Renal Cell Carcinoma Database Consortium criteria (concordance-index 0.75 vs 0.67, respectively), and distinguished two groups of patients within the original intermediate risk category.

CONCLUSIONS:

A prognostic model incorporating osteopontin, interleukin-6, TIMP-1, tumour burden, and selected clinical criteria increased prognostic accuracy for OS determination in mRCC patients.

• Authors: A J Zurita, R C Gagnon, Y Liu, H T Tran, R A Figlin, T E Hutson, A M D'Amelio Jr, C N Sternberg, L N Pandite, J V Heymach
• Journal: British journal of cancer (Br J Cancer) Vol. 117 Issue 4 Pg. 478-484 (Aug 08 2017) ISSN: 1532-1827 [Electronic] England
• PMID: 28683470 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Cytokines
• E-Selectin
• Hemoglobins
• Indazoles
• Interleukin-6
• Interleukin-8
• Pyrimidines
• Sulfonamides
• TIMP1 protein, human
• Tissue Inhibitor of Metalloproteinase-1
• Vascular Endothelial Growth Factor A
• Osteopontin
• Hepatocyte Growth Factor
• pazopanib
• L-Lactate Dehydrogenase

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Renal Cell (blood, drug therapy, mortality, pathology)
• Cytokines (blood)
• E-Selectin (blood)
• Female
• Hemoglobins (metabolism)
• Hepatocyte Growth Factor (blood)
• Humans
• Indazoles
• Interleukin-6 (blood)
• Interleukin-8 (blood)
• Kidney Neoplasms (blood, drug therapy, mortality, pathology)
• L-Lactate Dehydrogenase (blood)
• Leukocyte Count
• Male
• Middle Aged
• Neutrophils
• Osteopontin (blood)
• Prognosis
• Pyrimidines (therapeutic use)
• Sulfonamides (therapeutic use)
• Survival Rate
• Time-to-Treatment
• Tissue Inhibitor of Metalloproteinase-1 (blood)
• Tumor Burden
• Vascular Endothelial Growth Factor A (blood)