A cytokine and angiogenic factor (CAF) analysis in plasma for selection of sorafenib therapy in patients with metastatic renal cell carcinoma

Zurita, Amado J.; Jonasch, Eric; Wang, X; Khajavi, Mehrdad; Yan, Shaoyu; Du, D. Z.; Xu, Li; Herynk, Matthew H.; McKee, Kathryn S.; Tran, Hai T.; Logothetis, Christopher J.; Tannir, Nizar M.; Heymach, John V.

doi:10.1093/annonc/mdr047

Cited by 117 publications

(105 citation statements)

References 35 publications

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“…3B), consistent with the greater activity of ligand neutralization. Increased circulating VEGF concentrations have been observed with multiple inhibitors of angiogenic signaling pathways (5,16), and were confirmed in this patient cohort (6). Consistent with this, we found decreased tissue pERK at 2 weeks correlated with higher circulating VEGF concentration at both 2 and 6 weeks (r ϭ Ϫ0.60, p ϭ 0.024; r ϭ Ϫ0.63, p ϭ 0.0501, respectively; Table III).…”

Section: Resultssupporting

confidence: 88%

Translational Predictive Biomarker Analysis of the Phase 1b Sorafenib and Bevacizumab Study Expansion Cohort

Azad

Yu²,

Davidson

et al. 2013

Molecular & Cellular Proteomics

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Predictive biomarkers are needed to triage patients to the best therapy. We prospectively planned examination of sequential blood, biopsy, and functional imaging with which to confirm the mechanism and to identify potential predictive biomarkers in a phase Ib clinical trial expansion of patients with solid tumors receiving sorafenib/bevacizumab. The maximally tolerated doses of sorafenib at 200 mg twice daily with bevacizumab at 5 mg/kg every other week were given to biopsiable patients. Patients were randomized to receive either sorafenib or bevacizumab monotherapy for the first 28-day cycle with the second drug added with cycle 2. Biopsies, dynamic contrast-enhanced MRI, and fluorodeoxyglucose-proton emission tomography were done pre-therapy and at 2 and 6 weeks (2 weeks into combination therapy). Tumor and serum proteomics, Ras/Raf mutational analysis, and functional imaging results were examined individually and across the dataset to identify potential changes predictive of response to therapy and those that confirm the biochemical drug mechanism(s). Therapy with sorafenib/bevacizumab resulted in clinical benefit in 45% of this mixed solid tumor group. ERK activation and microvessel density were decreased with monotherapy treatment with sorafenib or bevacizumab, respectively; whereas a decreased signal over the group of total AKT, phospho(p)-VEGF receptor2, p-endothelial nitric-oxide synthase, b-RAF, and cleaved poly(ADP-ribose) polymerase was associated with earlier progression of disease. Tumor metabolic activity decreased in those patients with clinical benefits lasting longer than 4 months, and activity increased with progression of disease. Cleavage of caspase 3 and poly(ADPribose) polymerase was increased, and Ki67 expression decreased in patients with prolonged clinical benefits, consistent with decreased proliferation and increased apoptosis. The conglomerate analysis, incorporating pharmacodynamic and tumor biochemistry, demonstrated sorafenib/bevacizumab-targeted vascular activity in the tumor. Results suggest potential biomarkers for which changes, as a group, during early therapeutic exposure may predict clinical benefit. Molecular & Cellular

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Section: Resultssupporting

confidence: 88%

Translational Predictive Biomarker Analysis of the Phase 1b Sorafenib and Bevacizumab Study Expansion Cohort

Azad

Yu²,

Davidson

et al. 2013

Molecular & Cellular Proteomics

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“…Furthermore, it was confirmed that the development of other adverse events like HT (2,18), interstitial pneumonia (19) and a particular range of adverse events (1) was associated with the clinical outcome upon treatment with other molecular-targeted drugs. Although a variety of factors predictive of the clinical outcome upon treatment with sorafenib have been presented (10,11,20,21), all of these studies only focused on the variable of tumor grade. However, the combination of tumor-related factors and host-related factors represented by adverse events can be expected to enable more accurate estimation of the clinical outcome of sorafenib.…”

Section: Discussionmentioning

confidence: 99%

Hand-Foot Skin Reaction is Associated with the Clinical Outcome in Patients with Metastatic Renal Cell Carcinoma Treated with Sorafenib

Nakano

Kono

Kubo

et al. 2013

Japanese Journal of Clinical Oncology

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Background: To elucidate whether Hand -Foot skin reaction could become a biomarker of clinical outcome in patients with metastatic renal cell carcinoma treated with sorafenib, we retrospectively examined the association between the Hand -Foot skin reaction and the clinical outcome in metastatic renal cell carcinoma patients treated with sorafenib. Methods: Thirty-six Japanese metastatic renal cell carcinoma patients treated with sorafenib were enrolled and divided into the groups with or without Hand -Foot skin reaction. Patient characteristics, best tumor response, progression-free survival and adverse events were investigated and compared between these two groups. Results: A sorafenib-induced Hand -Foot skin reaction in metastatic renal cell carcinoma patients was observed at a significantly higher rate in patients in the favorable-risk group in the Memorial Sloan-Kettering Cancer Center risk classification, and with Eastern Cooperative Oncology Group Performance Status of one or less, prior nephrectomy, higher hemoglobin, lower lactate dehydrogenase and lower C-reactive protein. The mean best tumor response was significantly better in the group with Hand -Foot skin reaction (216.7%) than that in the group without it (17.9%; P , 0.001). The median progression-free survival was significantly longer in the group with Hand -Foot skin reaction (4.6 months) than that in the group without it (1.5 months; P ¼ 0.002). In multivariate analysis, only Hand -Foot skin reaction was shown to be a predictive factor of progression-free survival (hazard ratio 0.312, P ¼ 0.010). Conclusions: A sorafenib-induced Hand -Foot skin reaction in metastatic renal cell carcinoma patients emerged at a significantly higher rate in patients in the favorable-risk group in the Memorial Sloan-Kettering Cancer Center risk classification and was significantly associated with best tumor response and progression-free survival, suggesting that Hand -Foot skin reaction might be an independent predictive factor for clinical outcome in metastatic renal cell carcinoma patients treated with sorafenib.

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“…Specimens were obtained before the initiation of palliative chemotherapy. A total of 52 CAFs present in serum were analyzed with multiplex bead suspension array kits by means of the Bio-Plex 200 system according to the manufacturer's instructions (Bio-Rad Laboratories, Hercules, CA, USA), including human group I and group II cytokine panels as described in previous reports [21,22]. Serum concentrations of soluble carbonic anhydrase IX, soluble vascular endothelial growth factor receptor 2, placental growth factor, and osteopontin were determined by enzyme-linked immunosorbent assay (R&D Systems, Minneapolis, MN, USA).…”

Section: Sample Preparation and Caf Analysismentioning

confidence: 99%

Prognostic implication of antitumor immunity measured by the neutrophil–lymphocyte ratio and serum cytokines and angiogenic factors in gastric cancer

et al. 2016

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Background The neutrophil-lymphocyte ratio (NLR) is associated with a poor prognosis in many cancers but the biological mechanisms involved are unknown. Since cytokines and angiogenic factors (CAFs) are reflected by various immune responses, we analyzed the association between the NLR and CAFs and their prognostic implications in gastric cancer (GC). Methods Of 745 GC patients who were enrolled in NLR analysis, 70 underwent NLR and CAF association analyses. Pretreatment serum levels of 52 CAFs were measured by means of multiplex bead immunoassays and enzymelinked immunosorbent assays. Linear regression analysis and survival analysis of the NLR with each CAF were performed. Results Metastatic organ numbers and carbohydrate antigen 19-9 levels were significantly higher in patients with a high NLR [greater than 2.42 (median): P = 0.047 and P \ 0.001 respectively]. The overall survival was significantly worse in the high NLR group (17.8 months vs 11.2 months, P \ 0.001). In CAF analysis, osteopontin (R 2 = 0.337, P \ 0.001) and interleukin-6 (R 2 = 0.141, P = 0.001) were significantly associated with the NLR. Stromal-cell-derived factor 1 (SDF-1) was a significant poor prognostic factor independently of the NLR. Consideration of both the NLR and SDF-1 divided patient groups with different overall survival (both low, 21.0 months; either high, 15.8 months; both high, 8.2 months). Conclusion The NLR is a significant poor prognostic factor in advanced GC. The NLR is mainly associated with osteopontin and interleukin-6. Besides the NLR, SDF-1 is an independent poor prognostic factor in GC. Consideration of both the NLR and SDF-1 might give insights into antitumor immunity in GC.

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A cytokine and angiogenic factor (CAF) analysis in plasma for selection of sorafenib therapy in patients with metastatic renal cell carcinoma

Cited by 117 publications

References 35 publications

Translational Predictive Biomarker Analysis of the Phase 1b Sorafenib and Bevacizumab Study Expansion Cohort

Translational Predictive Biomarker Analysis of the Phase 1b Sorafenib and Bevacizumab Study Expansion Cohort

Hand-Foot Skin Reaction is Associated with the Clinical Outcome in Patients with Metastatic Renal Cell Carcinoma Treated with Sorafenib

Prognostic implication of antitumor immunity measured by the neutrophil–lymphocyte ratio and serum cytokines and angiogenic factors in gastric cancer

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