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...

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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

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Purpose Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit. This randomized, double-blind, placebo-controlled phase III study evaluated efficacy and safety of pazopanib monotherapy in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). Patients and Methods Adult patients with measurable, locally advanced, and/or metastatic RCC were randomly assigned 2:1 to receive oral pazopanib or placebo. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, tumor response rate (Response Evaluation Criteria in Solid Tumors), and safety. Radiographic assessments of tumors were independently reviewed. Results Of 435 patients enrolled, 233 were treatment naive (54%) and 202 were cytokine pretreated (46%). PFS was significantly prolonged with pazopanib compared with placebo in the overall study population (median, PFS 9.2 v 4.2 months; hazard ratio [HR], 0.46; 95% CI, 0.34 to 0.62; P .0001), the treatment-naive subpopulation (median PFS 11.1 v 2.8 months; HR, 0.40; 95% CI, 0.27 to 0.60; P .0001), and the cytokine-pretreated subpopulation (median PFS, 7.4 v 4.2 months; HR, 0.54; 95% CI, 0.35 to 0.84; P .001). The objective response rate was 30% with pazopanib compared with 3% with placebo (P .001). The median duration of response was longer than 1 year. The most common adverse events were diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. There was no evidence of clinically important differences in quality of life for pazopanib versus placebo. Conclusion Pazopanib demonstrated significant improvement in PFS and tumor response compared with placebo in treatment-naive and cytokine-pretreated patients with advanced and/or metastatic RCC. J Clin Oncol 28:1061-1068. © 2010 by American Society of Clinical Oncology

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Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(07)61904-7.pdf

Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial

Cyclophosphamide (CYP) treatment induces chemical cystitis leading to bladder overactivity (OAB) in animals and humans. There is a great number of OAB models evaluations, which consider the bladder histology, as well as alterations in neurochemical, electrophysiological properties of bladder afferent neurons and reflex arcs activity in the spinal cord. However there are no data differentiating cystometrically acute and chronic models of OAB induced by CYP under urethane anaesthesia. The aim of this study was to investigate the influence of acute and chronic models of CYP-induced cystitis on urinary bladder motor activity in rats.

Animal models of overactive bladder: cyclophosphamide (CYP)-induced cystitis in rats.

The increase of life intensity and its stressful impact, a great number of various risk factors of ED - erectile dysfunction and aging men population lead to a high prevalence and incidence of ED worldwide. It is well known that ED in men is a condition of heterogenous aetiology, which determines ED substantial diagnostic and therapeutic clinical problem. However, in most cases, ED may be managed quite well by the primary care physician who has proper understanding of the pathophysiology of ED. This article is intended especially for primary care physicians. It reviews physiology of erection and then explores pathophysiologic changes that are likely to cause inadequate erection, which enables better understanding of ED and consequently is essential for appropriate management.

Pathophysiology of erectile dysfunction in men.

Introduction: Aging induces autonomic nervous system (ANS) dysfunction with increased sympathetic drive. Benign Prostatic Hyperplasia (BPH) is responsible for lower urinary tract symptoms (LUTS), and its pathogenesis is com- plex. Exemplified by previous studies, the probably cause of BPH and secondary LUTS is due to the overly active sympa- thetic ANS resulting from aging. Objectives: The aim of our study was to estimate the ANS activity in BPH patients with LUTS using frequency domain analysis parameters of heart rate variability (HRV). Additionally, the relationship of ANS activity to the subjective meas- ures of LUTS, and the objective measures of BPH, as well as the biochemical and biometrical variables, were investi- gated. Material & methods: The study was performed on 30 men with LUTS secondary to BPH. The cohort of patients was asked to complete IPSS and quality of life questionnaires. We performed biometrical, biochemical measurements and urological estimations. Additionally, a serum sample was obtained for Prostate Specific Antigen and its derivatives analy- sis. ANS activity was assessed by HRV measurements in resting conditions, after simulation with deep breathing and by the tilt up test. In the HRV recording, frequency domain analysis parameters were calculated according to fast Fourier transformation and the correlation for ANS activity parameters vs BPH variables were analyzed. The following HRV pa- rameters were taken into consideration: VLF (power of very low frequency), LF (power of low frequency), LFnu (LF power in normalized units), HF (power of high frequency), HFnu (HF power in normalized), LF/HFnu (normalized ratio of LF power to HF power), PSD (total power of spectrum of the RR variability). Results: All participants (mean age 65 ± 7 years) presented moderate LUTS (IPSS = 14 pts.; QofL = 3 pts.) with Qave.= 7,4 ml/sec. and PVR = 48 ± 45 ml. Normalized values of LF and HF were 60.86 ± 18.96 (%) and 39.14 ± 18.96 (%), respec- tively. VLF - 238.75 ± 214.96 (ms 2 ). LF/HF ratio and its normalized value were 2.97 ± 3.04 (1) and 1.57 ± 1.40 (1), re- spectively. In response to deep breathing, significant increases of LF, LFnu, LF/HF, LF/HFnu and total power of HRV spectrum and a decrease of HFnu were observed. The E/I ratio was 1,12 ± 0,08. During the tilt up test, VLF, LFnu, LF/HF, and LF/HFnu were increased, while HFnu decreased. The 30/15 ratio was 0,98 ± 0,05. The observed strong corre- lations are as follows: 1) between prostate enlargement and HFnu and LFnu power; 2) between total PSA level and LFnu, HF, HFnu; 3) between free/total PSA ratio and LF/HFnu; 4) between PSA density of the transition zone and HF; 5) be- tween plasma noradrenalin level and HF; 6) between age and LFnu, HFnu, LF/HF and LF/HFnu; 7) between plasma adrenaline level and prostate enlargement: prostate length and transition zone height. Conclusions: These results demonstrate the sympathetic overactivity of ANS at rest in patients with BPH and LUTS. It is also suggested that in the pathophysiology of BPH, the heighten activity of the sympathetic ANS, and parasympathetic drive are important.

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Autonomic Nervous System Activity in Patients with Lower Urinary TractSymptoms Secondary to Benign Prostatic Hyperplasia Estimated by HeartRate Variability

Marek Filipek

Papers

Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial

Animal models of overactive bladder: cyclophosphamide (CYP)-induced cystitis in rats.

Pathophysiology of erectile dysfunction in men.

Autonomic Nervous System Activity in Patients with Lower Urinary TractSymptoms Secondary to Benign Prostatic Hyperplasia Estimated by HeartRate Variability