Phase I study of orally administered S-1 in combination with epirubicin and oxaliplatin in patients with advanced solid tumors and chemotherapy-naïve advanced or metastatic esophagogastric cancer.

BACKGROUND: This phase I study investigated the safety and the maximum tolerated dose (MTD) of the oral fluoropyrimidine S-1 when combined with epirubicin and oxaliplatin (EOS). METHODS: Patients aged ≥18 years with advanced or metastatic solid tumors were enrolled in a 3 + 3 design with S-1 dose escalation (two planned cohorts) performed according to the occurrence of dose-limiting toxicity (DLT). On day 1 of each 21-day cycle, patients received epirubicin 50 mg/m2 followed by oxaliplatin 130 mg/m2 (maximum 8 cycles) and then S-1 [20 mg/m2 (cohort 1) or 25 mg/m2 (cohort 2), twice daily]: first dose, evening of day 1; subsequent administration on days 2-14, twice daily; last dose, morning of day 15 (unlimited number of S-1 cycles). After protocol amendment, enrollment in a third cohort was restricted to patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer. RESULTS: DLT was reported for two of the five patients in cohort 2, defining 20 mg/m2 twice daily as the MTD of S-1 combined with epirubicin and oxaliplatin in heavily pretreated patients. Thirteen patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer were subsequently enrolled and treated at an S-1 dose level of 25 mg/m2 twice daily; no DLTs were reported; median overall survival was 13.1 months. Of the 11 evaluable patients, three (27 %) had partial responses and seven (64 %) had stable disease. The safety profile was in line with expectations. CONCLUSIONS: The promising activity of EOS (S-1 dose level, 25 mg/m2 twice daily) and acceptable safety profile support further clinical development of this combination for the first-line treatment of patients with advanced or metastatic esophagogastric cancer.

Indications and benefits of intraoperative esophagogastroduodenoscopy.

INTRODUCTION: Intraoperative esophagogastroduodenoscopy (IOG) is a diagnostic and therapeutic method for a variety of special conditions in upper gastrointestinal (UGI) pathology. The indication remains individual due to insufficient evidence and limited training of surgeons in digestive endoscopy. AIM: To evaluate the indications, benefits and risks of IOG. MATERIAL AND METHODS: A single-center retrospective study of 110 consecutive IOGs in 104 patients was performed. The preoperative plan, the timing of IOG, preoperative evaluation, intraoperative finding, localization of the pathology, type of the procedure, change of expected therapy and complications were assessed. RESULTS: The cohort comprised 29 esophageal tumors, 5 tumors of the cardia, 36 gastric tumors, gastrointestinal bleeding (8), esophageal diverticula (3), perforations (3), GERD (5), mediastinal pathology (3), fistula (4), assessment of nutrition (10), duodenal adenoma (2), ulcer disease, esophageal stenosis and gastric volvulus. The indication for IOG was established preoperatively in 79% and intraoperatively in 21%. The lesion was localized in 96.4%. The therapy was altered to a wider resection (11), smaller resection (5), localization and surgical therapy of bleeding (8) or allowed minimally invasive surgery (25). A total of 3 postoperative complications included gastric perforation and positivity of resection line (following EMR/ESD) and recurrent bleeding. The 30-day mortality reached 3.6% without a specific cause in IOG. CONCLUSIONS: The IOG is a complementary method in the diagnosis and treatment of UGI pathology. It enables minimally invasive finalization of the procedures and individualization of the therapy.

An enzymatic assay based on luciferase Ebola virus-like particles for evaluation of virolytic activity of antimicrobial peptides.

Antimicrobial peptides are currently considered as promising antiviral compounds. Current assays to evaluate the effectivity of peptides against enveloped viruses based on liposomes or hemolysis are encumbered by the artificial nature of liposomes or distinctive membrane composition of used erythrocytes. We propose a novel assay system based on enzymatic Ebola virus-like particles containing sensitive luciferase reporter. The assay was validated with several cationic and anionic peptides and compared with lentivirus inactivation and hemolytic assays. The assay is sensitive and easy to perform in standard biosafety level laboratory with potential for high-throughput screens. The use of virus-like particles in the assay provides a system as closely related to the native viruses as possible eliminating some issues associated with other more artificial set ups. We have identified CAM-W (KWKLWKKIEKWGQGIGAVLKWLTTWL) as a peptide with the greatest antiviral activity against infectious lentiviral vectors and filoviral virus-like particles.