Intermittent Versus Continuous Tarceva Study
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ABSTRACT:
DISEASE(S): Metastatic Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2098234 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:BackgroundCastration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence.MethodsMen with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization.ResultsA total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P=0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events.ConclusionsOur findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00002651.).
| S-EPMC3682658 | biostudies-literature
Project description:BackgroundPhototherapy is a widely accepted, effective first-line therapy for neonatal jaundice. It is traditionally used continuously but intermittent phototherapy has been proposed as an equally effective alternative with practical advantages of improved maternal feeding and bonding. The effectiveness of intermittent phototherapy compared with continuous phototherapy is unknown.ObjectivesTo assess the safety and effectiveness of intermittent phototherapy compared with continuous phototherapy.Search methodsSearches were conducted on 31 January 2022 in the following databases: CENTRAL via CRS Web, MEDLINE and Embase via Ovid. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials.Selection criteriaWe included RCTs, cluster-RCTs and quasi-RCTs comparing intermittent phototherapy with continuous phototherapy in jaundiced infants (both term and preterm) up to the age of 30 days. We compared intermittent phototherapy with continuous phototherapy by any method and at any dose and duration as defined by the authors.Data collection and analysisThree review authors independently selected trials, assessed trial quality and extracted data from included studies. We performed fixed-effect analyses and expressed treatment effects as mean difference (MD), risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CIs). Our primary outcomes of interest were rate of decline of serum bilirubin, and kernicterus. We used the GRADE approach to assess the certainty of evidence.Main resultsWe included 12 RCTs (1600 infants) in the review. There is one ongoing study and four awaiting classification. There was little or no difference between intermittent phototherapy and continuous phototherapy with respect to rate of decline of bilirubin in jaundiced newborn infants (MD -0.09 micromol/L/hr, 95% CI -0.21 to 0.03; I² = 61%; 10 studies; 1225 infants; low-certainty evidence). One study involving 60 infants reported no incidence of bilirubin induced brain dysfunction (BIND). It is uncertain whether either intermittent or continuous phototherapy reduces BIND because the certainty of this evidence is very low. There was little or no difference in treatment failure (RD 0.03, 95% CI 0.08 to 0.15; RR 1.63, 95% CI 0.29 to 9.17; 1 study; 75 infants; very low-certainty evidence) or infant mortality (RD -0.01, 95% CI -0.03 to 0.01; RR 0.69, 95% CI 0.37 to 1.31 I² = 0%; 10 studies, 1470 infants; low-certainty evidence). AUTHORS' CONCLUSIONS: The available evidence detected little or no difference between intermittent and continuous phototherapy with respect to rate of decline of bilirubin. Continuous phototherapy appears to be more effective in preterm infants, however, the risks of continuous phototherapy and the potential benefits of a slightly lower bilirubin level are unknown. Intermittent phototherapy is associated with a decrease in the total number of hours of phototherapy exposure. There are theoretical benefits to intermittent regimens but there are important safety outcomes that were inadequately addressed. Large, well designed, prospective trials are needed in both preterm and term infants before it can be concluded that intermittent and continuous phototherapy regimens are equally effective.
| S-EPMC9979775 | biostudies-literature
Project description:Obesity, a major risk factor for chronic diseases, is related to dsyfunctional adipose tissue signaling. First human trials suggest benefits of intermittent calorie restriction diet (ICR) in chronic disease prevention that may exceed those of continuous calorie restriction diet (CCR), even at equal net calorie intake. The effect of intermittent calorie restriction on adipose tissue signaling has not been investigated to date. Thus we initiated a randomized controlled trial to analyze the effect of ICR (eu-caloric diet on five days and two days per week with energy restriction of 75%), CCR (daily energy restriction of 20%) and a control group on subcutaneous adipose tissue (SAT) gene expression. 150 overweight or obese non-smoking adults (50 per group, 50% women) were randomly asiged to one of the study arms. SAT biopsies were taken before and after the 12 week intervention phase.
2019-03-01 | E-MTAB-5926 | biostudies-arrayexpress
Project description:Administration of enteral nutrition (EN) in critically ill pediatric patients admitted to the pediatric intensive care unit (PICU) constitutes a major challenge due to the increased risk of complications, as well as the lack of well-trained healthcare professionals. EN is usually delivered via cyclic, continuous, or intermittent feeding; however, a number of potential barriers have been reported in the literature regarding different feeding regimens. The purpose of this review was to assess the effectiveness of continuous and intermittent bolus feeding on critically ill children. A systematic search was conducted in PubMed, Scopus Cochrane Central Register of Controlled Trials (CENTRAL) and a clinical trial registry up to September 2022, including randomized controlled trials (RCTs) published in the English language. Four studies met the inclusion criteria with a total population of 288 patients admitted to the PICU. Three studies were rated with a high risk of bias and one with some concerns. There was high heterogeneity between the studies in regard to the reporting of outcomes. Three studies measured the total time needed to reach prescribed caloric intake with conflicting results, while two studies evaluated the length of stay (LOS) in PICU with no difference between the two arms. One study assessed the time weaning from mechanical ventilation, favoring the bolus group. No data were provided for gastric residual volume (GRV), anthropometric measurements, and biochemical markers. Additional randomized trials with better methodology are needed to assess the efficacy of the two enteral feeding regimens in critically ill PICU patients.
| S-EPMC9867148 | biostudies-literature
Project description:We conducted a systematic review and meta-analysis of randomized clinical trials and pilot trial studies to compare the effectiveness of intermittent fasting (IF) and continuous calorie restriction (CCR) in overweight and obese people. The parameters included body mass index (BMI), body weight, and other metabolism-related indicators. A systematic search in PubMed, Embase, Cochrane Library, and Web of Science was conducted up to January 2022. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to measure the effectiveness. Publication bias was assessed using Egger's test. The stability of the results was evaluated using sensitivity analyses. The significance of body weight change (SMD = -0.21, 95% CI (-0.40, -0.02) p = 0.028) was more significant after IF than CCR. There was no significant difference in BMI (SMD = 0.02, 95% CI (-0.16, 0.20) p = 0.848) between IF and CCR. These findings suggest that IF may be superior to CCR for weight loss in some respects.
| S-EPMC9099935 | biostudies-literature
Project description:The development of BRAF and MEK inhibitors (BRAFi/MEKi) has led to major advances in melanoma treatment. However, the emergence of resistance mechanisms limits the benefit duration and a complete response occurs in less than 20% of patients receiving BRAFi ± MEKi. In this study, we evaluated the impact of an intermittent versus continuous dosing schedule of BRAF/MEK inhibition in a melanoma model mildly sensitive to a BRAF inhibitor. The combination of a BRAFi with three different MEKi was studied with a continuous or intermittent dosing schedule in vivo, in a xenografted melanoma model and ex vivo using histoculture drug response assays (HDRAs) of patient-derived xenografts (PDX). To further understand the underlying molecular mechanisms of therapeutic efficacy, a biomarker pharmacodynamic readout was evaluated. An equal impact on tumor growth was observed in monotherapy or bitherapy regimens whether we used continuous and intermittent dosing schedules, with no significant differences in biomarkers expression between the treatments. The antitumoral effect was mostly due to modulations of expression of cell cycle and apoptotic mediators. Moreover, ex vivo studies did not show significant differences between the dosing schedules. In this context, our preclinical and pharmacodynamic results converged to show the similarity between intermittent and continuous treatments with either BRAFi or MEKi alone or with the combination of both.
| S-EPMC6931208 | biostudies-literature
Project description:BackgroundHemodynamic monitoring during digestive endoscopy is usually minimal and involves intermittent brachial pressure measurements. New continuous noninvasive devices to acquire instantaneous arterial blood pressure may be more sensitive to detect procedural hypotension.PurposeTo compare the ability of noninvasive continuous monitoring with that of intermittent oscillometric measurements to detect hypotension during digestive endoscopy.MethodsIn this observational prospective study, patients scheduled for gastrointestinal endoscopy and colonoscopy under sedation were monitored using intermittent pressure measurements and a noninvasive continuous technique (ClearSight™, Edwards). Stroke volume was estimated from the arterial pressure waveform. Mean arterial pressure and stroke volume values were recorded at T1 (prior to anesthetic induction), T2 (after anesthetic induction), T3 (gastric insufflation), T4 (end of gastroscopy), T5 (colonic insufflation). Hypotension was defined as mean arterial pressure < 65 mmHg.ResultsTwenty patients (53±17 years) were included. Six patients (30%) had a hypotension detected using intermittent pressure measurements versus twelve patients (60%) using noninvasive continuous monitoring (p = 0.06). Mean arterial pressure decreased during the procedure with respect to T1 (p < 0.05), but the continuous method provided an earlier warning than the intermittent method (T3 vs T4). Nine patients (45%) had at least a 25% reduction in stroke volume, with respect to baseline.ConclusionNoninvasive continuous monitoring was more sensitive than intermittent measurements to detect hypotension. Estimation of stroke volume revealed profound reductions in systemic flow. Noninvasive continuous monitoring in high-risk patients undergoing digestive endoscopy under sedation could help in detecting hypoperfusion earlier than the usual intermittent blood pressure measurements.
| S-EPMC7531858 | biostudies-literature
Project description:BackgroundIntermittent fasting is a time-restricted feeding strategy with proven health benefits, which is based on multiple metabolic and endocrine changes, in several patient populations and healthy participants. In the pediatric intensive care unit (PICU), artificial feeding is usually administered 24 hours a day, although solid evidence supporting this practice is lacking. This discards the potential benefits of fasting in this population. We hypothesize that intermittent nutrition with a focus on an overnight feeding interruption (intermittent fasting), as compared with 24-hour continuous nutrition, is a feasible and safe strategy, with potential benefits, for critically ill children.ObjectiveThe aim of the Continuous versus Intermittent Nutrition in Pediatric Intensive Care randomized controlled trial (RCT) is to investigate a strategy of intermittent nutrition with a focus on an overnight feeding interruption period versus 24-hour nutrition during the first 14 days in the PICU.MethodsThe Continuous versus Intermittent Nutrition in Pediatric Intensive Care study is an investigator-initiated RCT in a tertiary referral PICU. Critically ill children (term newborn to 18 years), expected to stay in the PICU for ≥48 hours, and dependent on artificial nutrition, are eligible for inclusion. This study will randomize critically ill children (n=140) to a continuous versus intermittent nutrition strategy. In both groups, similar daily caloric targets will be prescribed. In the continuous group (control), nutrition will be administered 24 hours a day, with a maximum interruption period of 2 hours. In the intermittent group (intervention), nutrition will be interrupted during an age-dependent overnight fasting period. The study intervention will last until admission day 14, initiation of oral intake, or discharge from the PICU, whichever comes first. The primary outcome is the difference in ketosis between the groups under the condition of noninferiority regarding caloric intake. Secondary outcomes are feeding intolerance; the proportion of severe and resistant hypoglycemic events and severe gastrointestinal complications; and additional observed effects on nutritional intake, circadian rhythm, and clinically relevant outcome measures of the intermittent feeding strategy compared with continuous nutrition.ResultsThe study was approved by the Dutch national ethical review board in February 2020. The first patient was enrolled on May 19, 2020. By May 2022, a total of 132 patients had been included in the study. Recruitment of the last patient is expected in Q3 2022.ConclusionsAlthough intermittent fasting has been proven to have many health benefits in both animal and human studies, the feasibility and safety of this strategy in a PICU setting must be investigated. This RCT will help physicians gain more insight into the feasibility, safety, and potential clinical effects of intermittent feeding with overnight fasting in critically ill children.Trial registrationNetherlands Trial Register NL7877; https://trialsearch.who.int/Trial2.aspx?TrialID=NL7877.International registered report identifier (irrid)DERR1-10.2196/36229.
| S-EPMC9264130 | biostudies-literature
Project description:The appropriate strategy for enteral feeding remains a matter of debate. We hypothesized that continuous enteral feeding would result in higher rates of achieving target nutrition during the first 7 days compared with intermittent enteral feeding. We conducted an unblinded, single-center, parallel-group, randomized controlled trial involving adult patients admitted to the medical intensive care unit who required mechanical ventilation to determine the efficacy and safety of continuous enteral feeding for critically ill patients compared with intermittent enteral feeding. The primary endpoint was the achievement of ≥80% of the target nutrition requirement during the first 7 days after starting enteral feeding. A total of 99 patients were included in the modified intention-to-treat analysis (intermittent enteral feeding group, n = 49; continuous enteral feeding group, n = 50). The intermittent enteral feeding group and continuous enteral feeding group received 227 days and 226 days of enteral feeding, respectively. The achievement of ≥80% of the target nutrition requirement occurred significantly more frequently in the continuous enteral feeding group than in the intermittent enteral feeding group (65.0% versus 52.4%, respectively; relative risk, 1.24; 95% confidence interval, 1.06-1.45; p = 0.008). For patients undergoing mechanical ventilation, continuous enteral feeding significantly improved the achievement of target nutrition requirements.
| S-EPMC8839656 | biostudies-literature
Project description:PURPOSE:To compare endocrine responses to intermittent vs continuous enteral nutrition provision during short-term bed rest. METHODS:Twenty healthy men underwent 7 days of bed rest, during which they were randomized to receive enteral nutrition (47%E as carbohydrate, 34%E as fat, 16%E as protein and 3%E as fibre) in a continuous (CONTINUOUS; n?=?10; 24 h day-1 at a constant rate) or intermittent (INTERMITTENT; n?=?10; as 4 meals per day separated by 5 h) pattern. Daily plasma samples were taken every morning to assess metabolite/hormone concentrations. RESULTS:During bed rest, plasma leptin concentrations were elevated to a lesser extent with INTERMITTENT vs CONTINUOUS (iAUC: 0.42?±?0.38 vs 0.95?±?0.48 nmol L-1, respectively; P?=?0.014) as were insulin concentrations (interaction effect, P?<?0.001) which reached a peak of 369?±?225 pmol L-1 in CONTINUOUS, compared to 94?±?38 pmol L-1 in INTERMITTENT (P?=?0.001). Changes in glucose infusion rate were positively correlated with changes in fasting plasma GLP-1 concentrations (r?=?0.44, P?=?0.049). CONCLUSION:Intermittent enteral nutrition attenuates the progressive rise in plasma leptin and insulinemia seen with continuous feeding during bed rest, suggesting that continuous feeding increases insulin requirements to maintain euglycemia. This raises the possibility that hepatic insulin sensitivity is impaired to a greater extent with continuous versus intermittent feeding during bed rest. To attenuate endocrine and metabolic changes with enteral feeding, an intermittent feeding strategy may, therefore, be preferable to continuous provision of nutrition. This trial was registered on clinicaltrials.gov as NCT02521025.
| S-EPMC7419443 | biostudies-literature