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PurposeEpigenetic aberrations have been reported in hepatocellular carcinoma (HCC). In this study of patients with unresectable HCC and chronic liver disease, epigenetic therapy with the histone deacetylase inhibitor belinostat was assessed. The objectives were to determine dose-limiting toxicity and maximum-tolerated dose (MTD), to assess pharmacokinetics in phase I, and to assess activity of and explore potential biomarkers for response in phase II.Patients and methodsMajor eligibility criteria included histologically confirmed unresectable HCC, European Cooperative Oncology Group performance score ≤ 2, and adequate organ function. Phase I consisted of 18 patients; belinostat was given intravenously once per day on days 1 to 5 every 3 weeks; dose levels were 600 mg/m(2) per day (level 1), 900 mg/m(2) per day (level 2), 1,200 mg/m(2) per day (level 3), and 1,400 mg/m(2) per day (level 4). Phase II consisted of 42 patients. The primary end point was progression-free survival (PFS), and the main secondary end points were response according to Response Evaluation Criteria in Solid Tumors (RECIST) and overall survival (OS). Exploratory analysis was conducted on pretreatment tumor tissues to determine whether HR23B expression is a potential biomarker for response.ResultsBelinostat pharmacokinetics were linear from 600 to 1,400 mg/m(2) without significant accumulation. The MTD was not reached at the maximum dose administered. Dose level 4 was used in phase II. The median number of cycles was two (range, one to 12). The partial response (PR) and stable disease (SD) rates were 2.4% and 45.2%, respectively. The median PFS and OS were 2.64 and 6.60 months, respectively. Exploratory analysis revealed that disease stabilization rate (complete response plus PR plus SD) in tumors having high and low HR23B histoscores were 58% and 14%, respectively (P = .036).ConclusionEpigenetic therapy with belinostat demonstrates tumor stabilization and is generally well-tolerated. HR23B expression was associated with disease stabilization.

Avelumab is a human anti-PD-L1 IgG1 monoclonal antibody that has shown antitumor activity in early phase studies in advanced/metastatic gastric/gastroesophageal junction cancer, including as first-line maintenance therapy. Here, we describe the design of JAVELIN Gastric 100 (NCT02625610), an open-label, Phase III trial. A total of 499 patients with locally advanced/metastatic HER2- gastric/gastroesophageal junction cancer adenocarcinoma, who had achieved at least stable disease following 12 weeks of first-line oxaliplatin/fluoropyrimidine chemotherapy, have been randomized 1:1 to receive avelumab maintenance therapy or continue chemotherapy. The primary objective is to demonstrate superior overall survival in all randomized patients or in the PD-L1+ population. Secondary objectives are to demonstrate superiority for progression-free survival and objective response rate, compare quality of life measures, and determine safety. [ABSTRACT FROM AUTHOR]

Background: Patients with advanced gastric or gastro-oesophageal junction cancer that progresses on chemotherapy have poor outcomes. We compared pembrolizumab with paclitaxel in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine.Methods: This randomised, open-label, phase 3 study was done at 148 medical centres in 30 countries. Eligible patients were randomised (1:1) in blocks of four per stratum with an interactive voice-response and integrated web-response system to receive either pembrolizumab 200 mg every 3 weeks for up to 2 years or standard-dose paclitaxel. Primary endpoints were overall survival and progression-free survival in patients with a programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or higher. Safety was assessed in all patients, irrespective of CPS. The significance threshold for overall survival was p=0·0135 (one-sided). This trial is registered at ClinicalTrials.gov, number NCT02370498.Findings: Between June 4, 2015, and July 26, 2016, 592 patients were enrolled. Of the 395 patients who had a PD-L1 CPS of 1 or higher, 196 patients were assigned to receive pembrolizumab and 199 patients were assigned to receive paclitaxel. As of Oct 26, 2017, 326 patients in the population with CPS of 1 or higher had died (151 [77%] of 196 patients in the pembrolizumab group and 175 [88%] of 199 patients in the paclitaxel group). Median overall survival was 9·1 months (95% CI 6·2-10·7) with pembrolizumab and 8·3 months (7·6-9·0) with paclitaxel (hazard ratio [HR] 0·82, 95% CI 0·66-1·03; one-sided p=0·0421). Median progression-free survival was 1·5 months (95% CI 1·4-2·0) with pembrolizumab and 4·1 months (3·1-4·2) with paclitaxel (HR 1·27, 95% CI 1·03-1·57). In the total population, grade 3-5 treatment-related adverse events occurred in 42 (14%) of the 294 patients treated with pembrolizumab and 96 (35%) of the 276 patients treated with paclitaxel.Interpretation: Pembrolizumab did not significantly improve overall survival compared with paclitaxel as second-line therapy for advanced gastric or gastro-oesophageal junction cancer with PD-L1 CPS of 1 or higher. Pembrolizumab had a better safety profile than paclitaxel. Additional trials of pembrolizumab in gastric and gastro-oesophageal cancer are ongoing.Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co. [ABSTRACT FROM AUTHOR]

In recent years, a number of studies have clearly pointed out the nutritional benefits of fish consumption. However, some concerns about potential health risks derived from contaminants found in fish have also been raised. Therefore, balancing adequately the risks and benefits of fish consumption is currently a health key issue. As tuna fish represents a large part of the traditional food in some countries, the possible impact of tuna fish consumption on public health was investigated. Hepatic damages following consumption of tuna fish white (ordinary) or red (dark) muscle were evaluated in rat. Under our experimental conditions, feeding the animals for 60 days with white or, more markedly, red tuna meat resulted in 1) an elevated uric acid level in blood, 2) an accumulation of lead in liver, 3) an atrophy of liver, 4) an increase in plasma aspartate aminotransferase and alanine aminotransferase activities, and 5) an oxidative stress in liver including an increased level of lipids peroxidation and enhanced activities of superoxide dismutase, catalase and glutathione peroxidase. In addition, liver histology revealed several abnormalities. These alterations could be attributed to both lead accumulation and high purine levels in tuna meat. We conclude that attention should be paid to a possible health impact of frequent and important consumption of tuna fish meat, especially the dark one. [ABSTRACT FROM AUTHOR]

The article presents a research which analyzes the efficacy of trastuzumab in combination with chemotherapy as compared to alone chemotherapy, for the treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer. It is reported that, trastuzumab is a monoclonal antibody against human epidermal growth factor receptor 2. It is reported that, the researchers of the research conducted an open-label international, phase 3, randomized controlled trial and named it Trastuzumab for Gastric Cancer (ToGA), and the research was undertaken in 122 centres in 24 countries. Researchers have concluded that trastuzumab combined with chemotherapy can be considered as a new standard option for patients suffering from HER2-positive advanced gastric or gastro-oesophageal junction cancer.

Purpose of Review: Gastric adenocarcinoma is the fifth most common and the third most lethal cancer worldwide. Surgery is the only chance of cure, but recurrence is common, even with complete resection. Recent Findings: Advances in diagnosis and staging, genomic classification, surgical resection and treatment of peritoneal disease, systemic chemotherapy and chemoradiation, and targeted and immune therapies have led to the current multidisciplinary approach to gastric adenocarcinoma. Summary: Treatment of gastric cancer is rapidly evolving in an effort to combat this challenging disease. [ABSTRACT FROM AUTHOR]