Predictive value of baseline serum vascular endothelial growth factor and neutrophil gelatinase-associated lipocalin in advanced kidney cancer patients receiving sunitinib

Porta, Camillo; Paglino, Chiara; Amici, Mara De; Quaglini, Silvana; Sacchi, Lucia; Imarisio, Ilaria; Canipari, Cinzia

doi:10.1038/ki.2009.552

Cited by 95 publications

(70 citation statements)

References 23 publications

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“…Its evaluation as a urine biomarker of renal cell carcinoma has not been reported previously. Although NGAL may not be a suitable biomarker of primary kidney cancer, a recent study found it may be used as a serum biomarker to follow the efficacy of treatment in patients with metastatic kidney cancer [39]. Our study shows that uNGAL excretion, although statistically significant, is clinically insignificant as NGAL concentrations were greater than those of controls in only 8 of 67 cancer patients.…”

Section: Discussionmentioning

confidence: 38%

Sensitivity and Specificity of Urinary Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 for the Diagnosis of Renal Cell Carcinoma

Morrissey

London

Lambert³

et al. 2011

Am J Nephrol

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Background/Aims: Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are urinary biomarkers of diagnostic relevance in a wide variety of acute and chronic kidney diseases. Their diagnostic sensitivity and specificity for kidney cancer are largely unknown and therefore the subject of this investigation. Methods: A prospective cohort study was performed to evaluate urine biomarkers for clear-cell and papillary subtypes of renal cancer (67 patients undergoing nephrectomy) and 55 control patients undergoing non-kidney surgery. Urinary KIM-1 and NGAL concentrations were determined by sensitive and specific ELISAs. Results: In renal cancer patients, median NGAL excretion was 0.52 (1st to 3rd quartiles: 0.28–0.82) ng/mg urinary creatinine (U_Cr) before nephrectomy compared to 0.15 (0.04–0.31) ng/mg U_Cr in controls (p < 0.001), and there was a modest decrease of 30% after nephrectomy (p < 0.008). NGAL was not correlated to tumor size (r = 0.19, p = 0.27) or stage. Before nephrectomy, KIM-1 excretion was 0.68 (0.40–1.12) ng/mg U_Cr compared to 0.03 (0.01–0.06) in controls (p < 0.001). There was a linear correlation between KIM-1 excretion before nephrectomy and tumor size (Spearman’s r = 0.66, p < 0.001), tumor stage, and a 50% decrease in median KIM-1 concentration 1 month following tumor excision (p < 0.01). Biomarker concentration ranges for renal cancer patients and controls overlapped substantially for NGAL but not KIM-1. Conclusion: NGAL is not a sensitive or specific urinary biomarker of kidney cancer. Although KIM-1 had diagnostic sensitivity for kidney cancer, it is well known to reflect many types of kidney injuries, thus limiting its specificity as a diagnostic biomarker for renal cancer.

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Section: Discussionmentioning

confidence: 38%

Sensitivity and Specificity of Urinary Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 for the Diagnosis of Renal Cell Carcinoma

Morrissey

London

Lambert³

et al. 2011

Am J Nephrol

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“…Baseline VEGF levels have been suggested to predict anti-tumor response to high-dose IL-2 and to VEGFR-targeted therapies [34,35]. In this study, no significant association between baseline VEGF levels and clinical efficacy endpoints (ORR or PFS) was observed (Additional file 1: Table S1).…”

Section: Resultsmentioning

confidence: 62%

Recombinant interleukin-21 plus sorafenib for metastatic renal cell carcinoma: a phase 1/2 study

Bhatia¹,

Curti²,

Ernstoff³

et al. 2014

j. immunotherapy cancer

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BackgroundDespite the positive impact of targeted therapies on metastatic renal cell carcinoma (mRCC), durable responses are infrequent and an unmet need exists for novel therapies with distinct mechanisms of action. We investigated the combination of recombinant Interleukin 21 (IL-21), a cytokine with unique immunostimulatory properties, plus sorafenib, a VEGFR tyrosine kinase inhibitor.MethodsIn this phase 1/2 study, 52 mRCC patients received outpatient treatment with oral sorafenib 400 mg twice daily plus intravenous IL-21 (10–50 mcg/kg) on days 1–5 and 15–19 of each 7-week treatment course. The safety, antitumor activity, pharmacokinetic and pharmacodynamic effects of the combination were evaluated.ResultsIn phase 1 (n = 19), the maximum tolerated dose for IL-21 with the standard dose of sorafenib was determined to be 30 mcg/kg/day; grade 3 skin rash was the only dose-limiting toxicity. In phase 2, 33 previously-treated patients tolerated the combination therapy well with appropriate dose reductions; toxicities were mostly grade 1 or 2. The objective response rate was 21% and disease control rate was 82%. Two patients have durable responses that are ongoing, despite cessation of both IL-21 and sorafenib, at 41+ and 30+ months, respectively. The median progression-free survival in phase 2 was 5.6 months. The pharmacokinetic and pharmacodynamic properties of IL-21 appeared to be preserved in the presence of sorafenib.ConclusionIL-21 plus sorafenib has antitumor activity and acceptable safety in previously treated mRCC patients. IL-21 may represent a suitable immunotherapy in further exploration of combination strategies in mRCC.Trial registrationClinicalTrials.gov Identifier: NCT00389285

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“…Unfortunately, the role of circulating VEGF and other clinical or molecular markers predictive of response to TKIs are still controversial [25]. The prognostic role of circulating tumour cells (CTCs) have been demonstrated in breast cancer [26] and other neoplasms, while their significance in RCC is still debated.…”

Section: Discussionmentioning

confidence: 99%

First-Line sunitinib in patients with renal cell carcinoma (RCC) in von Hippel–Lindau (VHL) disease: clinical outcome and patterns of radiological response

et al. 2014

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rate of radiological response, patterns of responses in different organs, treatment-related toxicities. We performed a retrospective analysis of sunitinib therapy in genetically-confirmed VHL patients treated at our Institution for multifocal or advanced RCC. From February 2007 to July 2012, 14 VHL patients started first-line sunitinib for recurrent or progressing RCC, mean age 48 years (27-71). Nine patients achieved a partial RECIST response (64.3%); responses were noted not only in renal and hepatic lesions but also in pancreatic nodules. Most lesions showed density reduction, while all CNS haemangioblastoma lesions remained stable. At a median follow-up of 37 months, six patients have progressed and three patients died, with a progression-free rate at 2 years of 71.4%. Sunitinib may therefore achieve a fairly good disease control in VHL patients. Radiological responses may be obtained not only in renal tumors but also in synchronous VHL-related lesions, especially pancreatic solid nodules whose exact nature (metastatic RCC or neuroendocrine tumor) cannot be ruled out without invasive biopsy.

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Predictive value of baseline serum vascular endothelial growth factor and neutrophil gelatinase-associated lipocalin in advanced kidney cancer patients receiving sunitinib

Cited by 95 publications

References 23 publications

Sensitivity and Specificity of Urinary Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 for the Diagnosis of Renal Cell Carcinoma

Sensitivity and Specificity of Urinary Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 for the Diagnosis of Renal Cell Carcinoma

Recombinant interleukin-21 plus sorafenib for metastatic renal cell carcinoma: a phase 1/2 study

First-Line sunitinib in patients with renal cell carcinoma (RCC) in von Hippel–Lindau (VHL) disease: clinical outcome and patterns of radiological response

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