Metastatic renal cell cancer treatments: An indirect comparison meta-analysis

Abstract Background Treatment for metastatic renal cell cancer (mRCC) has advanced dramatically with understanding of the pathogenesis of the disease. New treatment options may provide improved progression-free survival (PFS). We aimed to determine the relative effectiveness of new therapies in this field. Methods We conducted comprehensive searches of 11 electronic databases from inception to April 2008. We included randomized trials (RCTs) that evaluated bevacizumab, sorafenib, and sunitinib. Two reviewers independently extracted data, in duplicate. Our primary outcome was investigator-assessed PFS. We performed random-effects meta-analysis with a mixed treatment comparison analysis. Results We included 3 bevacizumab (2 of bevacizumab plus interferon-a [IFN-a]), 2 sorafenib, 1 sunitinib, and 1 temsirolimus trials (total n = 3,957). All interventions offer advantages for PFS. Using indirect comparisons with interferon-α as the common comparator, we found that sunitinib was superior to both sorafenib (HR 0.58, 95% CI, 0.38–0.86, P = < 0.001) and bevacizumab + IFN-a (HR 0.75, 95% CI, 0.60–0.93, P = 0.001). Sorafenib was not statistically different from bevacizumab +IFN-a in this same indirect comparison analysis (HR 0.77, 95% CI, 0.52–1.13, P = 0.23). Using placebo as the similar comparator, we were unable to display a significant difference between sorafenib and bevacizumab alone (HR 0.81, 95% CI, 0.58–1.12, P = 0.23). Temsirolimus provided significant PFS in patients with poor prognosis (HR 0.69, 95% CI, 0.57–0.85). Conclusion New interventions for mRCC offer a favourable PFS for mRCC compared to interferon-α and placebo

Sunitinib and other targeted therapies for renal cell carcinoma

Targeted therapy has radically altered the way metastatic renal cancer is treated. Six drugs are now licensed in this setting, with several other agents under evaluation. Sunitinib is currently the most widely used in the first line setting with impressive efficacy and an established toxicity profile. However, as further randomised studies report and as newer drugs become available this may change. In this review, we address our current understanding of targeted therapy in renal cancer. We also discuss areas in which our knowledge is incomplete, including the identification of correlative biomarkers and mechanisms of drug resistance. Finally, we will describe the major areas of clinical research that will report over the next few years

Costo-Efficacia di cabozantinib nel trattamento di seconda linea del tumore a cellule renali metastatico (mRCC) in Italia:

Introduction: Renal cell carcinoma (RCC) is the most common form of kidney cancer with >30% already metastatic at diagnosis. For patients who fail tyrosine kinase inhibitor (TKI) therapy, the Italian Medical Oncology Association recommends (level IA) nivolumab and cabozantinib. The aim of this study was to compare the cost-effectiveness of cabozantinib with nivolumab for treatment of adult patients with mRCC following prior TKI therapy in Italy. Methods: A partitioned survival (area under the curve) model was developed for the Italian medical environment. Cost-effectiveness was assessed from the Italian National Healthcare Service (SSN) perspective over a 30-year time horizon (annual discount: 3% rate). In the absence of head-to-head studies, clinical evidence was based on results of network meta-analysis. Health-state-related utilities were informed by EQ-5D data from the METEOR study. Resource use and costs were obtained from published sources. Results: Treatment with cabozantinib dominates nivolumab across a 30-years time horizon. In the reference case, treatment with cabozantinib results in an incremental 0.268 quality-adjusted life years (QALY) and an incremental 0.349 life years (LY) gained with a total saving, for the Italian SSN, of €5,605 compared to nivolumab over 30 years. Cabozantinib is associated with gains in quality adjusted life years versus nivolumab, in all analyses. Results were shown to be sensitive to drug prices variation and robust when altering other parameters. Discussion: Cabozantinib represents an efficient option in the management of mRCC after initial TKI-therapy in Italy. Drug prices impact final results, and this must be carefully considered, especially considering the confidential discounts and outcome/financial-based agreements currently in place in Italy

Long-term Safety of Sunitinib in Metastatic Renal Cell Carcinoma

Background Metastatic renal cell carcinoma (mRCC) patients receiving first-line sunitinib typically survive &gt;2 yr, with chronic treatment sometimes extending to ≥6 yr. Objective To analyze long-term safety with sunitinib in mRCC patients. Design, setting, and participants Data were pooled from 5739 patients in nine trials, comprising seven phase II studies, a phase III study, and an expanded-access trial in various treatment settings (e.g. cytokine refractory or treatment-naïve). Outcome measurements and statistical analysis Interval and cumulative time-period analyses evaluated the incidence of treatment-related adverse events (TRAEs) for up to 6 yr, in the overall population and in those with long-term (≥2 yr) sunitinib treatment. Results and limitations Among long-term patients (n=807), most TRAEs occurred initially in the first year and then decreased in frequency; TRAEs following this pattern included decreased appetite, diarrhea, dysgeusia, dyspepsia, fatigue, hypertension, mucosal inflammation, nausea, and stomatitis. However, hypothyroidism increased by interval analysis from 6% at 0-&lt;6 mo to 42% at 5-&lt;6 yr and by cumulative analysis from 14% at 0-&lt;1 yr to 36% over 6 yr. Grade 3/4 TRAEs in long-term patients peaked during the first year and then steadily decreased. The overall population displayed only minor differences from long-term patients, with no clinically significant differences between grade ≥3 TRAE profiles (&lt;5% difference in incidence rates at all intervals). Limitations included retrospective design, assessment variability, lack of pharmacokinetic data, and absence of baseline characteristics for long-term patients. Conclusions Prolonged sunitinib was not associated with new types or increased severity of TRAEs. Except hypothyroidism, toxicity was not cumulative. Patient summary More than 800 mRCC patients received sunitinib for between 2 and 6 yr without experiencing new or more severe treatment-related toxicity. Clinicians may be able to prescribe chronic sunitinib treatment for as long as patients continue to derive clinical benefit, without untoward additional risk

Maitrise de la salinité des eaux d'irrigation pour la viticulture

Même si la vigne reste parmi les plantes cultivées une des plus économes en eau, se pose maintenant la question de la disponibilité et de l'accessibilité à la ressource en eau naturelle de qualité: eaux souterraines (infiltration, nappes), eaux de surface stagnantes (lacs, retenues de barrages) ou en écoulement (rivières, fleuves), eaux de mer, eaux usées traitées (REUT). Certaines de ces eaux peuvent contenir des composés d'intérêts nutritionnels pour les plantes, mais aussi être riches en sels dissous. L'objet de cette communication est d'étudier les technologies permettant d'affiner la teneur en sel de l'eau d'irrigation pour la vigne, quel que soit son origine et son niveau initial. Les techniques membranaires, osmose inverse, nanofiltration et électrodialyse sont ainsi comparées techniquement et évaluées économiquement. Les unes, nanofiltration et osmose inverse, à partir de membranes poreuses ou denses sous pression, consiste en une séparation de quasi tous les éléments dissous de l'eau (anions, cations, mais y compris les nutriments azotés, et minéraux) et ce quel que soit, pour l'osmose inverse, la salinité de l'eau initiale (e.g. eau de mer). L'autre l'électrodialyse, à partir de membranes denses ne filtre pas l'eau, mais extrait une quantité pilotable en ligne, de sels dissous (Na+ et Cl− en particulier sélectionnables) sous l'effet d'un champ électrique, afin de l'adapter aux sols ou plantes concerné

Colloquium: Theory of Drag Reduction by Polymers in Wall Bounded Turbulence

The flow of fluids in channels, pipes or ducts, as in any other wall-bounded flow (like water along the hulls of ships or air on airplanes) is hindered by a drag, which increases many-folds when the fluid flow turns from laminar to turbulent. A major technological problem is how to reduce this drag in order to minimize the expense of transporting fluids like oil in pipelines, or to move ships in the ocean. It was discovered in the mid-twentieth century that minute concentrations of polymers can reduce the drag in turbulent flows by up to 80%. While experimental knowledge had accumulated over the years, the fundamental theory of drag reduction by polymers remained elusive for a long time, with arguments raging whether this is a "skin" or a "bulk" effect. In this colloquium review we first summarize the phenomenology of drag reduction by polymers, stressing both its universal and non-universal aspects, and then proceed to review a recent theory that provides a quantitative explanation of all the known phenomenology. We treat both flexible and rod-like polymers, explaining the existence of universal properties like the Maximum Drag Reduction (MDR) asymptote, as well as non-universal cross-over phenomena that depend on the Reynolds number, on the nature of the polymer and on its concentration. Finally we also discuss other agents for drag reduction with a stress on the important example of bubbles.Comment: Invited Colloquium Paper for Reviews of Modern Physics, 24 pages, 18 Figs., submitte

Challenges and opportunities for converting renal cell carcinoma into a chronic disease with targeted therapies

Optimum efficacy is the primary goal for any cancer therapy, and entails controlling tumour growth and prolonging survival as far as possible. The prognosis for patients with metastatic renal cell carcinoma (mRCC) has greatly improved with the introduction of targeted therapies. This review examines the development and efficacy of targeted agents for the management of mRCC, the challenges offered by their rapid emergence, and discusses how mRCC treatment may evolve in the future. Improvements in progression-free survival and overall survival rates, observed with targeted agents, indicate that it may now be possible to change mRCC from a rapidly fatal and largely untreatable condition into a chronic disease. The major challenges to further advances in targeted therapy for mRCC include overcoming drug resistance, identifying the most effective sequence or combination of targeted agents, optimising clinical trial design and managing the cost of treatment