ToRaRI (Tofacitinib in Rheumatoid Arthritis a Real-Life experience in Italy): Effectiveness, safety profile of tofacitinib and concordance between patient-reported outcomes and physician's global assessment of disease activity in a retrospective study in Central-Italy.

INTRODUCTION: The use of Janus Kinase Inhibitors (JAK-Is) in rheumatoid arthritis (RA) has entered in daily practice. In consideration of ORAL-Surveillance trial and the new EULAR recommendations, real-world data are needed to assess Jak-Is safety and effectiveness. The multicenter study presented here aimed to evaluate effectiveness and safety of tofacitinib in a real-life cohort. METHODS: A retrospective analysis was performed from September 2021 to December 2022. Data were collected when tofacitinib was started (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. The primary objective was to analyze the efficacy and safety of tofacitinib. Safety was assessed by recording adverse events (AEs) with and without discontinuation. The secondary objective was to assess the difference between Patient-Reported Outcomes (PROs) and Physician's Global Assessment of disease activity (PhGA). RESULTS: 122 patients were included in the study from the following rheumatology Centers: Pisa, Ancona, Florence (two Centers), Siena, and Sardinia. A statistically significant improvement in DAS-28-CRP, CDAI and SDAI score was observed at T3, T6, compared to baseline (p < 0.001). Improvement was confirmed in patients who reach T12. Patients naïve to bDMARDs showed a shorter remission time and higher remission rates. There was also a statistically significant improvement in PROs compared to baseline (p < 0.001). The improvement was rapid and was consistent with PhGA. The 12-month retention rate for tofacitinib was 89.35%. Reasons to stop tofacitinib were: insufficient response (7), gastrointestinal symptoms (2), infection (1), malignancy (1), Zoster (1), pruritus sine materia (1). CONCLUSIONS: Tofacitinib is safe and effective in our RA cohort. It induces higher remission rates in patients naive to bDMARDs, suggesting that there may be a benefit using it as first-line therapy. Additionally, improvement in PROs was consistent with PhGA scores, demonstrating how tofacitinib affects both the objective and subjective components of disease activity. Key Points 1. JAK inhibitors are considered at a similar level as biologic agents in terms of effectiveness. 2. After ORAL-Surveillance results, real-world data are needed to assess the benefit/risk profile of Jaki. 3. Disagreement between patients and physicians has been previously reported with biologic therapy among patients with rheumatoid arthritis, with patients rating disease activity higher than physicians. 4. Jak inhibitors could reduce this discrepancy, due to their mechanism of action.

Cost-Effectiveness of Vonoprazan Compared With Proton Pump Inhibitors in Patients Taking Low-Dose Aspirin for Secondary Prevention of Cardiovascular Events in Japan.

BACKGROUND: Low-dose aspirin (LDA) is used to prevent recurrent cardiovascular (CV) events, but is associated with upper gastrointestinal (GI) bleeding; concomitant use of a proton pump inhibitor (PPI) reduces this risk. This study aimed to assess the cost-effectiveness of vonoprazan compared with PPIs (lansoprazole and esomeprazole) in patients taking LDA for secondary prevention of CV events.Methods and Results: A Markov simulation model was developed to predict the number of GI bleeding and acute CV events using 3 strategies (vonoprazan+LDA, esomeprazole+LDA, and lansoprazole+LDA), which were translated into quality-adjusted life-years (QALYs) and costs. Transition probabilities and utilities were derived from the results of published literature, and medical costs were based on the Japanese National Health Insurance fee table and claims databases in 2020. Outcomes were projected over 30 years starting at age 65 years and discounted at 2% annually. Expected costs with esomeprazole 20 mg, lansoprazole 15 mg and vonoprazan 10 mg were JPY 1,225,657, JPY 943,930, and JPY 1,059,510, respectively. The QALY gain for vonoprazan vs. esomeprazole was 0.35, thus vonoprazan was dominant against esomeprazole. The QALY gain for vonoprazan vs. lansoprazole was 0.29 and the incremental cost-effectiveness ratio (ICER) was JPY 398,551, thus, vonoprazan was more cost-effective than lansoprazole. CONCLUSIONS: Vonoprazan is dominant or cost-effective compared with esomeprazole and lansoprazole in patients taking LDA for secondary prevention of CV events.

An economic evaluation of tofacitinib for the treatment of moderately-to-severely active ulcerative colitis: modeling the cost of treatment strategies in the United States.

Aims: To evaluate the cost differences between a treatment strategy including tofacitinib (TOFA) vs treatment strategies including adalimumab (ADA), golimumab (GOL), infliximab (IFX), and vedolizumab (VEDO) among all patients with moderate-to-severe ulcerative colitis (UC) (further stratified by patients naïve/exposed to tumor necrosis factor inhibitors [TNFis]). Materials and methods: An Excel-based decision-analytic model was developed to evaluate costs from the perspective of a third-party US payer over 2 years. Efficacy and safety parameters were taken from prescribing information and published trials. All patients started induction therapy on the first treatment in the strategy and continued if efficacy criteria were met and no major adverse event occurred (in which cases they proceeded to the next treatment in the strategy). Results: The cost per member per month (PMPM) of the TOFA->IFX->VEDO->GOL strategy ($1.11) was lower than that of the ADA->IFX->VEDO->GOL strategy ($1.34; Δ = $-0.23) among the TNFi-naïve population (n = 204 patients out of a plan of one million members). Similarly, the use of TOFA before ADA (i.e. TOFA->ADA->IFX-> VEDO) was also associated with lower PMPM costs than the use of ADA before TOFA (i.e. ADA->TOFA->IFX->VEDO): $1.15 vs $1.25 (Δ = $-0.10). Similar, and often larger, differences were observed in both the overall moderate-to-severe population and the TNFi-exposed population. Sensitivity analyses resulted in the same conclusions. Limitations: Our model relied on efficacy data from prescribing information and published trials, which were not head-to-head and slightly differed with respect to methods. Additionally, our model used representative minor and major ADRs (and the associated costs) to represent toxicity management, which was a simplifying assumption. Conclusions: This analysis, the first of its kind to evaluate TOFA vis-à-vis other advanced therapies in the US, suggests the early use of TOFA among both TNFi-naïve and TNFi-failure patients results in lower PMPM costs compared with other treatment alternatives.

Risk for Herpes Zoster in Tofacitinib-Treated Rheumatoid Arthritis Patients With and Without Concomitant Methotrexate and Glucocorticoids.

OBJECTIVE: Increased incidence of herpes zoster (HZ) has been observed with JAK inhibitors such as tofacitinib. However, whether concomitant methotrexate (MTX) and/or glucocorticoids confer additional (additive or multiplicative) risk is unclear. We evaluated HZ risk in tofacitinib users with and without MTX and glucocorticoids. METHODS: Within MarketScan and Medicare data (2011-2016), we identified all patients with rheumatologist-diagnosed rheumatoid arthritis initiating treatment with tofacitinib (index date); demographics and baseline covariates were evaluated in the year prior to the index date. HZ was ascertained using International Classification of Diseases, Ninth Revision or Tenth Revision codes with antiviral drug use (±7 days). Multivariable Cox regression was used to evaluate hazard ratios (HRs) for HZ in tofacitinib users with and without current concomitant MTX and glucocorticoids, controlling for baseline covariates. RESULTS: We studied 8,030 new tofacitinib users (83.3% women). The mean ± SD age was 60.3 ± 12.6 years. HZ incidence in tofacitinib users was numerically lowest in the absence of glucocorticoids (3.4 per 100 patient-years with MTX; 3.7 per 100 patient-years without MTX). An approximately 2-fold increased incidence of HZ was observed for tofacitinib users receiving either glucocorticoids alone (6.0 per 100 patient-years) or both MTX plus glucocorticoids (6.5 per 100 patient-years). The adjusted HR for HZ in tofacitinib users was unchanged (HR 0.99 [95% confidence interval (95% CI) 0.64-1.54]) when given only with MTX, but was increased (HR 1.96 [95% CI 1.33-2.88]) for tofacitinib plus glucocorticoids. Older age and female sex were also risk factors, while prior vaccination was associated with a strong trend for lower risk. CONCLUSION: In tofacitinib users, HZ occurred at a rate of approximately 4% per year and was further doubled with glucocorticoid exposure. Concomitant MTX did not confer additional risk. Zoster vaccination may decrease risk.

An Economic Evaluation of Tofacitinib Treatment in Rheumatoid Arthritis After Methotrexate or After 1 or 2 TNF Inhibitors from a U.S. Payer Perspective.

BACKGROUND: Treatment cycling with biologic disease-modifying anti-rheumatic drugs, such as tumor necrosis factor inhibitors (TNFi), is common among patients with rheumatoid arthritis (RA) and can result in reduced clinical efficacy and increased economic burden. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. OBJECTIVE: To evaluate and compare the economic effect of tofacitinib 5 mg twice daily (BID) treatment directly after methotrexate (MTX) in the MTX-inadequate responder population, or after MTX and 1 TNFi (adalimumab [ADA] or etanercept [ETN]) or 2 TNFi (ADA and ETN) in TNF-inadequate responder patients with RA, from a U.S. payer perspective. METHODS: A decision-tree economic model was used to evaluate costs over 2 years. Treatment response was modeled as American College of Rheumatology (ACR) 20/50/70 response. ACR response rates at 6-month intervals were derived from U.S. prescribing information for monotherapy and combination therapy. Safety event rates were sourced from a meta-analysis. It was assumed that 75% of patients switched therapy after an adverse event or lack of response. Cost inputs included drugs, monitoring and administration (including physician visits), health care utilization, and treatment for adverse events. The population comprised all organization members (i.e., RA and non-RA members); RA patients receiving TNFi were estimated using epidemiologic data. Results were based on an organization size of 1 million. Economic endpoints were total 2-year costs, costs per member per month (PMPM), and costs per ACR20/50 responder. RESULTS: 1,321 patients were included for analysis. Based on ACR20 switch criteria and either 100% or 50% monotherapy rates for all treatments, total 2-year costs and costs PMPM were lower for patients receiving tofacitinib as second-line therapy after MTX and as third-line therapy after MTX and 1 TNFi; costs were highest for patients who cycled through 2 TNFi. Similar trends were observed for switch criteria based on ACR50 response and addition of 20% rebates for ADA and ETN and 0% for tofacitinib, although differences were mitigated slightly. CONCLUSIONS: A treatment strategy with tofacitinib as either second- or third-line therapy after MTX may be a lower cost treatment option, compared with fourth-line introduction of tofacitinib after cycling through 2 TNFi following MTX. DISCLOSURES: All aspects of this study were funded by Pfizer. Claxton was an employee of York Health Economics Consortium, University of York, at the time of this study. Taylor is an employee of York Health Economics Consortium, The University of York, which received funding from Pfizer to conduct this study. Soonasra, Bourret, and Gerber are employees of Pfizer and hold stock/stock options in Pfizer. A previous iteration of the data reported in this manuscript (before adjustment for recent drug price increases) was presented at the Academy of Managed Care Pharmacy 28th Annual Meeting and Expo; April 19-22, 2016; held in San Francisco, CA.

Significance of Age in Japanese Patients Receiving Sunitinib as First-line Systemic Therapy for Metastatic Renal Cell Carcinoma: Comparative Assessment of Efficacy and Safety between Patients Aged <75 and ≥75 Years.

BACKGROUND/AIM: To date, it has not been well characterized whether sunitinib is effective in elderly patients with metastatic renal cell carcinoma (mRCC). The objective of this study was to investigate the impact of age on clinical outcomes of mRCC patients receiving sunitinib. PATIENTS AND METHODS: The efficacy and safety of first-line sunitinib in 154 consecutive mRCC patients were retrospectively compared between patients aged <75 (n=125) and ≥75 (n=29) years. RESULTS: There were no significant differences in the major clinicopathological characteristics between younger and older patients; however, the reduction of the initial dose of sunitinib was significantly more frequent in older than younger patients. No significant difference in response rate, clinical benefit rate or proportion of patients going on to receive second-line therapy was noted between these two groups. Furthermore, there was no significant difference in progression-free survival (PFS) or overall survival (OS) between the two groups, and no significant impact of age on PFS or OS was documented by the Cox proportional hazards regression analyses. Of several adverse events, only anemia and fatigue were significantly more frequently observed in older than younger patients. Although there was no significant difference in the incidence of dose reduction or discontinuation of sunitinib between the two groups, the interruption of sunitinib was more frequently required in older than younger patients. CONCLUSION: These findings suggest that advanced age alone should not be regarded as a contraindication to the introduction of sunitinib as first-line systemic therapy for mRCC patients.

Herpes Zoster in Patients Receiving JAK Inhibitors For Ulcerative Colitis: Mechanism, Epidemiology, Management, and Prevention.

Increased risk of herpes zoster (HZ) has been observed in patients with immune-mediated diseases, including rheumatoid arthritis (RA), psoriasis (PsO), and inflammatory bowel disease; this risk can be further increased by the use of immunosuppressive therapy. One advancing modality of therapy for these diseases is Janus kinase (JAK) inhibition. Tofacitinib is an oral JAK inhibitor for the treatment of RA and psoriatic arthritis, which is currently under investigation for the treatment of ulcerative colitis (UC) and was previously investigated for psoriasis. JAK inhibitors have been associated with HZ events in patients across a number of indications. The pathogenesis underlying this risk of HZ is currently unknown. An increased risk of HZ has been noted in patients receiving immunosuppressive therapies for UC, including tofacitinib. In clinical trials, there was a dose-dependent risk of HZ (higher dose linked with increased risk). However, the majority of HZ cases are nonserious and noncomplicated, mild to moderate in severity, and manageable without permanent discontinuation of treatment. This review will discuss HZ risk in patients receiving JAK inhibitors, focusing on tofacitinib with respect to the potential mechanisms and epidemiology of HZ. Current guidelines for the prevention of HZ will be highlighted, and proposed management reviewed.

Clinical and Economic Outcomes in Elderly Advanced Renal Cell Carcinoma Patients Starting Pazopanib or Sunitinib Treatment: A Retrospective Medicare Claims Analysis.

INTRODUCTION: Studies indicate similar survival and toxicity between pazopanib and sunitinib, but few have examined real-world outcomes among elderly patients with advanced renal cell carcinoma (RCC). The purpose of this retrospective claims analysis was to assess real-world overall survival (OS), healthcare resource utilization (HRU), and healthcare costs (both all-cause and associated with RCC diagnosis) among elderly advanced RCC patients starting pazopanib or sunitinib treatment. METHODS: Advanced RCC patients aged 65 years or older who started first-line treatment with pazopanib or sunitinib (index drug; the initiation date was the index date) were identified from the 100% Medicare database plus Part D linkage (January 1, 2006 to December 31, 2014). Patients were stratified by index drug and matched 1:1 with use of propensity scores based on baseline characteristics. OS was assessed from the index date to death and compared by Kaplan-Meier analyses and univariable Cox models; patients were censored at the end of eligibility/data. Monthly HRU and costs from an intent-to-treat perspective were compared by Wilcoxon signed-rank tests. RESULTS: Baseline characteristics were balanced after matching (both N = 522). Treatment with pazopanib was associated with significantly longer median OS compared with treatment with sunitinib (18.2 months vs 14.6 months, respectively; log-rank p = 0.015). Pazopanib was associated with significantly lower monthly all-cause costs compared with sunitinib ($8845 vs $10,416, respectively), as well as lower inpatient costs associated with RCC diagnosis ($1542 vs $2522), fewer monthly inpatient admissions (0.179 vs 0.262), and shorter length of inpatient stay (1.375 days vs 1.883 days; all p ≤ 0.004). CONCLUSIONS: Among elderly Medicare patients with advanced RCC, first-line pazopanib tretament was associated with significantly longer OS, as well as lower healthcare costs and HRU, compared with first-line sunitinib treatment.

Treatment Patterns and Burden of Illness in Patients Initiating Targeted Therapy or Chemotherapy for Pancreatic Neuroendocrine Tumors.

OBJECTIVE: The aim of this study was to characterize treatment patterns and burden of pancreatic neuroendocrine tumors (PNET). METHODS: Using 2 claims databases, we identified patients with PNET initiating targeted therapy (everolimus, sunitinib) or chemotherapy from 2009 to 2012. The first targeted/cytotoxic therapy was considered index treatment. Treatment patterns were graphically evaluated from index treatment initiation until enrollment or study end, whichever occurred first. Disease burden was examined by index group for first follow-up year. RESULTS: In treatment pattern analyses (582 newly treated patients with PNET), 72.2% received chemotherapy index treatment, 16.2% everolimus, and 11.7% received sunitinib. Median index treatment duration was 242, 146, and 126 days for everolimus, sunitinib, and cytotoxics (P < 0.01). Sunitinib initiators switched most often followed by everolimus and cytotoxic initiators. In disease burden analyses, 338 patients met inclusion criteria, with mean age of 54.5 (standard deviation, 9.9) years, 45.6% were female, and there were no significant between-group differences. Targeted therapy initiators had more prior somatostatin analog use versus cytotoxics (53.4% vs 25.1%, P < 0.001); 72.5% had comorbidities after treatment initiation; 42.9% had 1 or more inpatient hospitalization; and 47.9% had 1 or more emergency department visit. CONCLUSIONS: Pancreatic neuroendocrine tumor treatment patterns varied; cytotoxics were more often used as early therapy than targeted agents, but for less time. Patients had high health care utilization, irrespective of treatment, potentially from burdensome symptoms and comorbidities.

[Tyrosine kinase inhibiting the VEGF pathway and elderly people: Tolerance, pre-treatment assessment and side effects management]. / Inhibiteurs de tyrosine kinase ciblant l'angiogenèse et sujets âgés : tolérance, évaluation pré-thérapeutique et gestion des effets indésirables.

Angiogenesis inhibition is a major antitumor strategy that has emerged during the last decade. Oral tyrosine kinase inhibitors (TKI) targeting the VEGF receptor, including sunitinib, sorafenib, axitinib, regorafenib, pazopanib, and vandetanib reduce tumor growth and metastasis. These agents are approved for the treatment of metastatic diseases in first or second-line. They display a narrow therapeutic index. However, data in the elderly and/or in patients with multiple illnesses remain scarce. This population is classically excluded from clinical trials. The aim of this review is to provide an overview of existing literature regarding antiangiogenic TKI tolerance in the elderly (>70 years old). We also highlight key points of the pre-therapeutic evaluation and summarize the management of common toxicities.

Sunitinib dosing schedule 2/1 improves tolerability, efficacy, and health-related quality of life in Chinese patients with metastatic renal cell carcinoma.

PURPOSE: To assess the efficacy and tolerability of sunitinib dosing schedule of 2 weeks on and 1 week off (schedule 2/1) vs. the traditional schedule of 4 weeks on and 2 week off (schedule 4/2) and its influence on health-related quality of life (HRQoL) in Chinese patients with metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: A retrospective analysis of 108 patients with mRCC who were treated with sunitinib regimens (50mg daily) between January 2009 and July 2013 was undertaken. Overall, 3 groups of patients were studied according to the dosing schedule they received: schedule 4/2 (n = 50), transitional schedule 2/1 (T2/1; patients switched from schedule 4/2 to 2/1; n = 26), and initial schedule 2/1 (I2/1; n = 32). The tumor response, progression-free survival (PFS) time, adverse events, and HRQoL were assessed and compared among the groups. RESULTS: The incidences of diarrhea, fatigue, hand-foot syndrome, and neutropenia induced by the treatment of sunitinib were all significantly less common with schedule I2/1 and T2/1 than with schedule 4/2 (P<0.05). Although there was no statistically significant difference in the tumor response among the 3 groups, the median PFS time was significantly longer with schedule I2/1 than with schedules T2/1 and 4/2 (11.2 vs. 9.4 and 9.5mo, respectively, P = 0.030), and HRQoL (as determined by 19-item Functional Assessment of Cancer Therapy Kidney Symptom Index scores) was better. CONCLUSIONS: Treatment with sunitinib 50mg daily using a 2/1 dosing schedule can provide better tolerability and a longer PFS with better HRQoL in Chinese patients with mRCC than the traditional schedule 4/2.

Assessment of Sunitinib-Induced Toxicities and Clinical Outcomes Based on Therapeutic Drug Monitoring of Sunitinib for Patients With Renal Cell Carcinoma.

BACKGROUND: Sunitinib has been approved for the treatment of metastatic renal cell carcinoma (RCC). Sunitinib pharmacokinetics shows a large interpatient variability. PATIENTS AND METHODS: A retrospective, observational clinical study of 21 patients with RCC was performed. Sunitinib was administered for 4 weeks of a 6-week cycle for the first cycle. We evaluated the association of sunitinib-induced toxicities and clinical outcomes with the trough total sunitinib concentration in a steady state during the first cycle. RESULTS: The median total sunitinib concentration was 91.8 ng/mL (range, 49.8-205 ng/mL). There was an association between total sunitinib concentration and the severity of thrombocytopenia, anorexia, and fatigue. Patients with ≥ 100 ng/mL total sunitinib (n = 8), compared with patients with < 100 ng/mL (n = 13), had a greater incidence of Grade ≥ 3 toxicities (6 patients [75.0%] vs. 3 patients [23.1%]). Patients with < 100 ng/mL total sunitinib had significantly longer time to treatment failure (TTF) and progression-free survival (PFS) time than patients with ≥ 100 ng/mL (median TTF, 590 vs. 71 days; P = .04; median PFS, 748 vs. 238 days; P = .02). CONCLUSION: Results of this study suggest that therapeutic drug monitoring of sunitinib could be useful for avoiding severe toxicities. Dose reduction might be needed, especially when the total sunitinib concentration is ≥ 100 ng/mL, to avoid unnecessary early discontinuation of treatment.

Health care costs among renal cancer patients using pazopanib and sunitinib.

BACKGROUND: Pazopanib was noninferior to sunitinib in progression-free survival in a phase III, open-label, randomized clinical trial comparing the efficacy and safety of the 2 drugs for treatment of patients with advanced renal cell carcinoma (RCC). A secondary analysis of this trial conducted on patient-reported health care resource utilization (HCRU) endpoints revealed significantly fewer monthly telephone consultations and emergency department visits among patients treated with pazopanib over the first 6 months of treatment. OBJECTIVES: To (a) compare total costs of HCRU and adverse events (AEs) in patients with advanced RCC receiving first-line pazopanib or sunitinib from the phase III clinical trial and (b) perform a post hoc economic analysis that applied direct medical care and pharmacy unit costs, obtained from the Truven Health MarketScan Databases, to HCRU and AE rates. METHODS: Total HCRU costs included components for provider contacts, diagnostics, hospitalizations, procedures, and study/nonstudy drugs. Patients were stratified by the presence or absence of an AE in order to estimate costs attributable to AEs. Costs were adjusted to 2013 U.S. dollars. The highest 1% of cost outliers were equally excluded from each group. Univariate (t-test and Kaplan-Meier sample average [KMSA]) and multivariate (using treatment group and region as covariates) analyses were performed. RESULTS: A total of 906 patients (pazopanib, n = 454; sunitinib, n = 452) reported HCRU; higher rates were observed for sunitinib. In unadjusted cost analyses, the mean total costs for pazopanib-treated patients were 8.0% lower than those treated with sunitinib ($80,464 vs. $86,886; P = 0.20). The difference in KMSA-estimated costs was significantly higher for sunitinib versus pazopanib ($156,128 vs. $143,585; P = 0.003). Adjusted cost differences between arms consistently suggested higher costs for sunitinib. Among patients who experienced greater than or equal to 1 AE, costs were $8,118 higher for pazopanib-treated patients and $14,343 for sunitinib-treated patients. CONCLUSIONS: The findings suggest that health care costs were lower among patients with advanced RCC treated first-line with pazopanib versus sunitinib.

Assessment of efficacy, safety and quality of life of 110 patients treated with sunitinib as first-line therapy for metastatic renal cell carcinoma: experience in real-world clinical practice in Japan.

The objective of this study was to comprehensively evaluate the clinical outcomes of 110 consecutive Japanese patients who received at least two cycles of sunitinib as first-line therapy for metastatic renal cell carcinoma (mRCC) in a routine clinical setting. Initially, 50 mg of sunitinib was administered once daily on a 4 weeks on, followed by 2 weeks off dosing schedule; however, dose modification was required in 102 patients, and the relative dose intensity was 62.6 % throughout this series. As the best responses to sunitinib, 2, 28, 65 and 15 were judged to show a complete response, partial response, stable disease and progressive disease, respectively. The median progression-free survival (PFS) and overall survival (OS) following the treatment with sunitinib were 7.8 and 33.2 months, respectively. Multivariate analyses of several factors identified the following independent predictors of PFS and OS: Memorial Sloan Kettering Cancer Center (MSKCC) classification and C-reactive protein (CRP) level for PFS and liver metastasis, MSKCC classification and CRP level for OS. The common adverse events related to sunitinib corresponding to ≥grade 3 were thrombocytopenia in 59, leukopenia in 23, fatigue in 22, hand-foot syndrome in 15 and hypertension in 12. Quality of life (QOL) analysis using 36-Item Short Form revealed no significant differences in any scale scores between surveys performed before and 3 months after the treatment with sunitinib. Collectively, these findings suggest that the introduction of sunitinib as a first-line agent can lead to favorable disease control with acceptable tolerability, resulting in improvement in the prognosis and QOL of Japanese patients with mRCC.

Efficacy and safety of alternate day therapy with atorvastatin and fenofibrate combination in mixed dyslipidemia: a randomized controlled trial.

INTRODUCTION: The long half-life of atorvastatin and fenofibrate makes them suitable for alternate day therapy. Hence, we aimed to study the efficacy, safety, and cost-effectiveness of alternate day therapy with atorvastatin and fenofibrate combination in mixed dyslipidemia. METHODS: Eligible patients with mixed dyslipidemia were randomly allotted into 2 equal parallel groups-alternate day therapy group (group 1) and daily therapy group (group 2). Patients in groups 1 and 2 received fixed dose combination of atorvastatin 10 mg and fenofibrate 160 mg on alternate days and daily, respectively, for 12 weeks. Mean percentage change from baseline in triglycerides (TGLs), non-high-density lipoprotein cholesterol (non-HDL-C), HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and TC-HDL ratio, incidence of adverse effects, and cost-effectiveness were compared in both the groups. RESULTS: Among 110 patients randomized, 99 completed the study till 12 weeks treatment duration. The TGLs, non-HDL-C, TC, and LDL-C decreased by 56.4%, 49.7%, 36.5%, and 39.2%, respectively, in alternate day therapy group and by 57.5%, 51.2%, 37.5%, and 39.4%, respectively, in daily therapy group. The HDL-C levels increased by 20.1% in alternate day therapy group compared to 21.8% in daily therapy group. No statistically significant difference was seen between both the groups in mean percentage change in lipid parameters from baseline to end of 12 weeks. Incidence of adverse events was reasonably less in alternate day therapy group. CONCLUSION: Alternate day therapy with atorvastatin-fenofibrate combination is an effective and safe alternative to daily therapy in mixed dyslipidemia. Apart from significant cost savings, reasonable reduction in the incidence of adverse events is seen with alternate day regimen. However, larger studies are needed to more reliably confirm our interesting but preliminary results.

Effects of adding statins before surgery on mortality and major morbidity: a meta-analysis.

OBJECTIVE: To re-evaluate the effects of adding a statin before surgery on mortality at 30 days and at 1 year and on major morbidity at 0-30 days. DESIGN: A meta-analysis of parallel, randomized, controlled trials published in English. SETTING: A university-based electronic search. PARTICIPANTS: Adult patients undergoing any type of procedure. INTERVENTION: Adding a statin before a procedure compared to a placebo or no intervention. MEASUREMENTS AND MAIN RESULTS: A search for all randomized controlled trials (RCT) was done in PubMed, Embase, Ovid MEDLINE and the Cochrane Central Register of Controlled Trials in November 2012. The quality of each study was assessed with the Cochrane Collaboration Tools. An I-square ≥ 25% was chosen as the cut-off point for heterogeneity exploration. The search produced 29 trials. Statins reduced the 0-30 days' risk of myocardial infarction: risk ratio (RR) 0.48 (95%CI 0.38, 0.61); I-square 13.2%; p<0.001; number needed-to-treat 17 (14, 24). There were no statistical differences at 0-30 days for stroke RR 0.70 (0.25, 1.95), acute renal insufficiency RR 0.54 (0.26, 1.12) or reoperation RR 1.10 (0.51, 2.38). There was a trend for a reduced mortality at 1 year RR 0.26 (0.06, 1.02); I-square 0%; p = 0.053. The hospital length of stay was slightly decreased with atorvastatin: standardized mean difference (SMD) -0.27 (-0.39, -0.14), p<0.001; fluvastatin SMD -0.95 (-1.56, -0.34), p = 0.002; and rosuvastatin SMD -0.69 (-0.98, -0.40), p<0.001 but not with simvastatin SMD -0.04 (-0.41, 0.48). CONCLUSIONS: Adding a statin before a high risk cardiac procedure reduces the 0-30 days' risk of myocardial infarction.

Assessment of the safety and efficiency of sunitinib malate in metastatic neuroendocrine tumours of the pancreas (NEN G1/G2) depending on the number and type of earlier therapeutic lines - initial report.

INTRODUCTION: The objective of this paper was to assess the safety and efficacy of sunitinib malate in patients with well-differentiated metastatic pancreatic neuroendocrine neoplasms (PNENs) who relapsed on standard therapy. MATERIAL AND METHODS: Overall, eight patients with well-differentiated pancreatic neuroendocrine tumours/neoplasm (NET/NEN G1/G2, Ki-67 < 20%), who had relapsed on a standard therapy approach, were treated. All had non-resectable, progressive disease. All received therapy using a standard dose of sunitinib malate. Adverse events were evaluated using NCI-CTC AE v. 3.0. RESULTS: Of the eight patients, seven had non-secretor and single secretor tumour (gastrinoma). Partial remission (PR) was noted in three patients (one after a single therapeutic line, two after two lines), five patients had stabilisation (SD) - including three individuals after three lines, one patient after two lines and another after a single line. Haematological adverse events: leukopenia (25%) - occurred in one patient after three lines and in one patient after two lines; anaemia (25%) - in one patient after three lines and in one patient after one therapeutic line. Mucocutaneous lesions were noted in 37.5% of patients after 2-3 lines of treatment. All of them experienced fatigue syndrome irrespective of the number of therapies. The majority of the patients simultaneously received somatostatin analogues, which did not exacerbate the toxicity profile. The median progression-free survival time (PFS) was 11 months. CONCLUSIONS: Sunitinib may be considered as a fairly well-tolerated and effective therapeutic option in progressive non-resectable PNEN patients in the second and subsequent lines of treatment, irrespective of the types of treatment previously applied.