Benefits of immunonutrition in patients with head and neck cancer receiving chemoradiation: A phase II randomized, double-blind study.

BACKGROUND & AIMS: The benefits of immunonutrition in patients with head and neck cancer (HNC), especially for those undergoing definitive concurrent chemoradiation (CCRT), remain unclear. We evaluated the benefits of immunonutrition regarding the prevention of severe oral mucositis. Secondary objectives included assessments of other treatment-related toxicities, changes of nutritional and inflammatory marker levels, treatment tolerance, and survival. METHODS: In total, 110 patients with HNC undergoing definitive CCRT including 3-week cycles of cisplatin were enrolled in our double-blind phase II study. Patients were randomly assigned to receive an immunonutrient formula containing omega-3-fatty acids, arginine, dietary nucleotides, and soluble fiber (n = 55) or an isocaloric isonitrogenous control (n = 55). All patients received the assigned product 5 consecutive days before each chemotherapy session. The proportion of patients with severe oral mucositis was compared between the immunonutrients and control groups. RESULTS: The rates of nasopharyngeal cancer (NPC) were 67% and 51% in the immunonutrients and control groups, respectively. All patients had 100% compliance to the assigned product. There was no difference of the proportion of patients with grade 3-4 oral mucositis between the two groups (62% vs. 67%, p = 0.690). At the time of analyses, survival tended to be better in the immunonutrients group. The 3-year progression-free survival rates were 69% (95% confidence interval [CI] = 55%-80%) and 44% (95% CI = 30%-57%) in the immunonutrients and control groups, respectively (p = 0.056), whereas the 3-year overall survival rates in these groups were 69% (95% CI = 54%-80%) and 50% (95% CI = 36%-66%; p = 0.065), respectively. In subgroup analyses according to the primary tumor location, the survival benefits were apparently maintained in patients with NPC. CONCLUSIONS: Although our study did not demonstrate a reduced risk of severe oral mucositis, we found that immunonutrition might improve survival. Larger studies are needed to determine the optimal dose and schedule of immunonutrition to prevent oral mucositis. In addition, randomized phase III trials evaluating the survival benefits of immunonutrition in patients with cancer are required, and NPC might be a primary malignancy of interest. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05101889.

Enteral nutrition formulations for acute pancreatitis.

BACKGROUND: Acute pancreatitis is a common and potentially lethal disease with increasing incidence. Severe cases are characterised by high mortality, and despite improvements in intensive care management, no specific treatment relevantly improves clinical outcomes of the disease. Meta-analyses suggest that enteral nutrition is more effective than conventional treatment consisting of discontinuation of oral intake with use of total parenteral nutrition. However, no systematic review has compared different enteral nutrition formulations for the treatment of patients with acute pancreatitis. OBJECTIVES: To assess the beneficial and harmful effects of different enteral nutrition formulations in patients with acute pancreatitis. SEARCH METHODS: We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Specialised Register of Clinical Trials, the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 7), MEDLINE (from inception to 20 August 2013), EMBASE (from inception to 2013, week 33) and Science Citation Index-Expanded (from 1990 to August 2013); we conducted full-text searches and applied no restrictions by language or publication status. SELECTION CRITERIA: We considered randomised clinical trials assessing enteral nutrition in patients with acute pancreatitis. We allowed concomitant interventions if they were received equally by all treatment groups within a trial. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and extracted data. We performed the analysis using Review Manager 5 (Review Manager 2013) and both fixed-effect and random-effects models. We expressed results as risk ratios (RRs) for dichotomous data, and as mean differences (MDs) for continuous data, both with 95% confidence intervals (CIs). Analysis was based on an intention-to-treat principle. MAIN RESULTS: We included 15 trials (1376 participants) in this review. We downgraded the quality of evidence for many of our outcomes on the basis of high risk of bias. Low-quality evidence suggests that immunonutrition decreases all-cause mortality (RR 0.49, 95% CI 0.29 to 0.80). The effect of immunonutrition on other outcomes from a subset of the included trials was uncertain. Subgrouping trials by type of enteral nutrition did not explain any variation in effect. We found mainly very low-quality evidence for the effects of probiotics on the main outcomes. One eligible trial in this comparison reported a higher rate of serious adverse events leading to increased organ failure and mortality due to low numbers of events and low risk of bias. When we excluded this study as a post hoc sensitivity analysis, risks of mortality (RR 0.30, 95% CI 0.10 to 0.84), organ failure (RR 0.74, 95% CI 0.59 to 0.92) and local septic complications (RR 0.40, 95% CI 0.22 to 0.72) were lower with probiotics. In one trial assessing immunonutrition with probiotics and fibres, no deaths occurred, but hospital stay was shorter with immunonutrition (MD -5.20 days, 95% CI -8.73 to -1.67). No deaths were reported following semi-elemental enteral nutrition (EN), and the effect on length of hospital stay was small (MD 0.30 days, 95% CI -0.82 to 1.42). Fibre-enriched formulations reduced the number of other local complications (RR 0.52, 95% CI 0.32 to 0.87) and length of hospital stay (MD -9.28 days, 95% CI -13.21 to -5.35) but did not significantly affect all-cause mortality (RR 0.23, 95% CI 0.03 to 1.84) and other outcomes. Very low-quality evidence from the subgroup of trials comparing EN versus no intervention showed a decrease in all-cause mortality with EN (RR 0.50, 95% CI 0.29 to 0.86). AUTHORS' CONCLUSIONS: We found evidence of low or very low quality for the effects of immunonutrition on efficacy and safety outcomes. The role of supplementation of enteral nutrition with potential immunomodulatory agents remains in question, and further research is required in this area. Studies assessing probiotics yielded inconsistent and almost contrary results, especially regarding safety and adverse events, and their findings do not support the routine use of EN enriched with probiotics in routine clinical practice. However, further research should be carried out to try to determine the potential efficacy or harms of probiotics. Lack of trials reporting on other types of EN assessed and lack of firm evidence regarding their effects suggest that additional randomised clinical trials are needed. The quality of evidence for the effects of any kind of EN on mortality was low, and further studies are likely to have an impact on the finding of improved survival with EN versus no nutritional support. Evidence remains insufficient to support the use of a specific EN formulation.

5-Fluorouracil, mitomycin-c, and polysaccharide-k versus uracil-ftorafur and polysaccharide-K as adjuvant chemoimmunotherapy for patients with locally advanced gastric cancer with curative resection.

BACKGROUND: Despite the small but significant survival benefit of adjuvant chemotherapy in locally advanced gastric cancer (LAGC), the optimal regimen remains to be determined. We conducted a randomized trial comparing oral (PO) chemoimmunotherapy (CITX) with intravenous (IV) CITX in LAGC patients (stages IB-IIIB) with curative resection (≥ D2 dissection). METHODS: The patients were randomized to the IV (5-fluorouracil 500 mg/m(2) weekly for 24 weeks, mitomycin-C 8 mg/m(2) every 6 weeks × 4) or the PO (uracil-ftorafur (UFT) 400-600 mg/day for 12 months) group. Patients in both groups received PO polysaccharide-K (3 g/day for 4 months). The planned number of patients was 368 for proving the non-inferiority of PO CITX compared to IV CITX for overall survival. RESULTS: The trial was closed prematurely after enrolling 82 patients (44 in the IV group, 38 in the PO group). With a median follow-up of 82 months, there were no significant differences in the 5-year disease-free survival (73% vs. 55%, p = 0.358) and overall survival (77% vs. 66%, p = 0.159) between the 2 groups. The IV group demonstrated a higher incidence of grade 2 or 3 neutropenia, thrombocytopenia, and vomiting. CONCLUSIONS: PO CITX with UFT appeared to be at least non-inferior to 5-fluorouracil and mitomycin-C CITX, with lower toxicity in the adjuvant treatment for LAGC.

No improvement in renal cell carcinoma survival: a population-based study in the Netherlands.

BACKGROUND: The increased finding of kidney 'incidentalomas' and more frequent surgery in patients with renal cell cancer (RCC) metastases may have improved survival from the disease. However, recent data on survival of unselected population-based series of patients with RCC are sparse. METHODS: We collected the follow-up data for all the patients registered with RCC in the population-based cancer registry held by the Comprehensive Cancer Centre East, the Netherlands. RESULTS: Patients (1504) diagnosed with RCC between 1989 and 2002 were included. Eighty-three percent of all tumours were histologically confirmed; 17% of all diagnoses were based on clinical examination only. The latter group was older, had a worse stage distribution, often did not receive any kind of therapy and showed a 5-year relative survival of 8%. Five-year relative survival for patients with a histologically confirmed RCC was 60% and did not improve over the last 15 years. A low resection rate in patients with metastasis was observed, most pronounced in elderly, without a tendency of increase in more recent years. CONCLUSION: The relative survival of RCC did not improve over the years. The resection rate in patients with metastasised disease did not increase over time, despite current knowledge concerning its benefit on tumour complications, time to progression and response to immunotherapy.