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Prognostic biomarkers for patients with advanced renal cell carcinoma treated with VEGF-targeted tyrosine kinase inhibitors.

ABSTRACT: Tyrosine kinase inhibitors with activity against vascular endothelial growth factor receptor 2 are now standard treatment for the majority of patients with advanced renal cell carcinoma. The clinical development of these agents followed by their broad clinical utilization has allowed the creation of large databases to facilitate the identification of prognostic biomarkers and development of prognostic models. While several clinical prognostic models have been created, work continues on identifying novel biomarkers which might be used in conjunction with or even in place of these clinical models. In this review, we discuss the progress thus far in improving on current prognostic models and speculate on possible developments in the near future.

SUBMITTER: Cho DC

PROVIDER: S-EPMC3684228 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Prognostic biomarkers for patients with advanced renal cell carcinoma treated with VEGF-targeted tyrosine kinase inhibitors.

Cho Daniel C DC

OncoTargets and therapy 20130613

Tyrosine kinase inhibitors with activity against vascular endothelial growth factor receptor 2 are now standard treatment for the majority of patients with advanced renal cell carcinoma. The clinical development of these agents followed by their broad clinical utilization has allowed the creation of large databases to facilitate the identification of prognostic biomarkers and development of prognostic models. While several clinical prognostic models have been created, work continues on identifyi ...[more]

PMID: 23788835

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Predictive value of De Ritis ratio in metastatic renal cell carcinoma treated with tyrosine-kinase inhibitors.

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The Impact of Renal Impairment on Survival Outcomes in Patients With Metastatic Renal Cell Carcinoma Treated With Tyrosine Kinase Inhibitors.

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Immunoscore System for Predicting Clinical Outcome of Metastatic Renal Cell Carcinoma Patients Treated with Tyrosine Kinase Inhibitors.

Project description:We conducted this study to determine whether immunoscore system (IS) predicts survival in patients with metastatic renal cell carcinoma (mRCC). A total of 218 mRCC patients treated with sunitinib or sorafenib in Zhongshan Hospital, Fudan University were recruited during 2007-2017, retrospectively. CD8, CD4, Treg, PD-1 and PD-L1 expression were evaluated by immunohistochemical staining of paraffin embedded slide. Kaplan-Meier method and COX regression model were used in survival analyses. Multivariate analyses demonstrated that expressions of CD8, Treg, PD-1 and stromal PD-L1 (sPD-L1) expressions were independent predictive factors for OS, thus IS was established containing these four immunological factors. Subsequent analysis revealed that performance of IS provided good differentiation of OS and PFS. Besides, multivariate analysis identified IS as an independent prognostic factor for OS (p<0.001) and PFS (p=0.002). IS, compared with International mRCC Database Consortium (IMDC) risk model, and provided better prediction ability for OS. Results suggested that IS was a powerful prognostic factor for OS and PFS in patients with mRCC treated with tyrosine kinase inhibitors. And IS can be used as essential supplement to IMDC for outcome prediction in mRCC patients.

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Safety and activity of temsirolimus and bevacizumab in patients with advanced renal cell carcinoma previously treated with tyrosine kinase inhibitors: a phase 2 consortium study.

Project description:PurposeBevacizumab or temsirolimus regimens have clinical activity in the first-line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent.MethodsIn the phase I portion, eligible patients were treated with temsirolimus (25 mg IV weekly) and escalating doses of IV bevacizumab (level 1 = 5 mg/kg; level 2 = 10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression-free rate. Secondary endpoints were response rate, toxicity evaluation, and PFS and OS.ResultsMaximum tolerated dose was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (temsirolimus 25 mg IV weekly and bevacizumab 10 mg/kg IV every 2 weeks). The 6-month progression-free rate was 40 % (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response, stable disease, and progressive disease were seen in 23, 63, and 14 % of patients, respectively. Most common grade 3-4 AEs included fatigue (17.8 %), hypertriglyceridemia (11.1 %), stomatitis (8.9 %), proteinuria (8.9 %), abdominal pain (6.7 %), and anemia (6.7 %). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively.ConclusionsTemsirolimus and bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population.

| S-EPMC4348698 | biostudies-literature

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