BackgroundNivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment. MethodsA total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily. The primary end point was overall survival. The secondary end points included the objective response rate and safety. ResultsThe median overall survival was 25.0 months (95% confidence interval [CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 23.1) with everolimus. The haz...

/pdf/nivolumab-versus-everolimus-in-advanced-renal-cell-carcinoma-4qkp9zdhuq.pdf

Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

https://rihuc.huc.min-saude.pt/bitstream/10400.4/1818/1/renal%20cell%20carcinoma.pdf

EAU Guidelines on Renal Cell Carcinoma: 2014 Update

Background Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma. Methods We randomly assigned adults in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The coprimary end points were overall survival (alpha level, 0.04), objective response rate (alpha level, 0.001), and progression-free survival (alpha level, 0.009) among patients with intermediate or poor prognostic risk. Results A total of 1096 patients were assigned to receive nivolumab plus ipilimumab (550 patients) or sunitinib (546 patients); 425 and 422, respectively, had intermediate or poor risk. At a median follo...

/pdf/nivolumab-plus-ipilimumab-versus-sunitinib-in-advanced-renal-4ntr0q1kl0.pdf

Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma

http://marc.porneuf.pagesperso-orange.fr/biblio/references/Efficacy%20of%20everolimus%20in%20advanced%20renal%20cell%20carcinoma%20a%20double-blind,%20randomised,%20placebo-controlled%20phase%20III%20trial.pdf

Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial

Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.

/pdf/comprehensivemolecular-characterization-of-clear-cell-renal-3ziuct29hu.pdf

Comprehensivemolecular characterization of clear cell renal cell carcinoma

Background Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability. Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, may benefit patients with this disease. Methods In this multicenter, phase 3 trial, we randomly assigned 626 patients with previously untreated, poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly, 3 million U of interferon alfa (with an increase to 18 million U) subcutaneously three times weekly, or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly. The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group. Results Patients who received temsirolimus alone had longer overall survival (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P=0.008) and progression-free survival (P<0.001) than did patie...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa066838

Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma.

Purpose Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR1), -2, and -3. This phase III trial compared tivozanib with sorafenib as initial targeted therapy in patients with metastatic renal cell carcinoma (RCC). Patients and Methods Patients with metastatic RCC, with a clear cell component, prior nephrectomy, measurable disease, and 0 or 1 prior therapies for metastatic RCC were randomly assigned to tivozanib or sorafenib. Prior VEGF-targeted therapy and mammalian target of rapamycin inhibitor were not permitted. The primary end point was progression-free survival (PFS) by independent review. Results A total of 517 patients were randomly assigned to tivozanib (n = 260) or sorafenib (n = 257). PFS was longer with tivozanib than with sorafenib in the overall population (median, 11.9 v 9.1 months; hazard ratio [HR], 0.797; 95% CI, 0.639 to 0.993; P = .042). One hundred fifty-six patients (61%) who progressed on sorafenib crossed over to rece...

/pdf/tivozanib-versus-sorafenib-as-initial-targeted-therapy-for-3cgnw3lcn8.pdf

Tivozanib Versus Sorafenib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma: Results From a Phase III Trial

Urological oncology: renal, ureteral and retroperitoneal tumors

The aim: to study the X-ray density index (HU) in calcium-containing urinary stones with different structural and compositional features. The structural and compositional features of 118 samples of calcium-containing urinary stones, which were obtained as a result of extracorporeal shock wave lithotripsy, percutaneous nephrolithotripsy and ureteroscopic lithotripsy in patients with kidney and ureteral stones were studied. The structural features of the stones were evaluated by conducting a crystal-optical analysis, during which the linear dimensions, shape, color and degree of transparency of crystalline elements were estimated, and the volume fractions of the amorphous and crystalline phases in the sample structure were calculated. The compositional features of kidney stones were studied on the basis of a qualitative and quantitative assessment of their mineral composition by infrared spectroscopy. X-ray density of calcium-containing kidney stones was assessed based on the data of computed tomography without contrast, which was performed in all patients in the preoperative period. Structural and compositional features of calcium-containing urinary stones are characterized by the presence in their composition of calcium oxalate compounds in the form of vewellite and weddelite, as well as calcium phosphate in the form of apatite, hydroxylapatite, fluorapatite, carbonate apatite, which, depending on the stage of crystallization, can be in amorphous, amorphous-crystalline or crystalline state. The X-ray density of this type of urinary stones, according to multislice computed tomography, corresponds to the range of 1090-1785 HU. There is a direct correlation between the level of X-ray density of the stone and the volume fraction of the crystalline phase in its structure.

Vladimir Lesovoy

Papers

Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma.

Tivozanib Versus Sorafenib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma: Results From a Phase III Trial

Urological oncology: renal, ureteral and retroperitoneal tumors

Possibilities of multislice computed tomography in assessing the structural and compositional features of calcium-containing urinary stones