No abstract

Medical personnel actively provide patients taking capecitabine with information on the items to prevent and treat hand-foot syndrome (HFS). However, they are typically unable to ascertain the extent of patient compliance with the recommended items. Thus, the aim of the present study was to ascertain the association between patient compliance with preventative measures for HFS and the development of HFS. Subjects included 90 patients who were treated with a drug regimen that included capecitabine. Patients were treated at one of four facilities between July 2015 and January 2017. The main parameters studied were the extent to which items to prevent and treat HFS were (or were not) followed, and the associaiton between this extent and the development of HFS symptoms. A manual prepared by a pharmaceutical company that manufactures capecitabine describes 15 routine items to follow in order to prevent and treat HFS. The two activities patients most often performed were 'applying a moisturizer' (74.1%) and 'keeping one's skin clean (e.g., washing one's hands and feet)' (64.7%). The two activities patients least often performed were 'using sunscreen on exposed areas' (14.1%) and 'using soft insoles' (11.8%). Patients who performed more items to prevent and treat HFS were significantly less likely to develop symptoms of HFS (P=0.022). Based on these findings, it is recommended that medical personnel provide instructions to the patients regarding the specific items necessary to prevent and treat HFS, and to follow-up with the patients regarding their compliance, with an emphasis on the items they are less likely to take and on the instructions to avoid external irritants. Following these guidelines should lead to qualitative improvement in HFS management.

The purpose of this study was to examine whether tetrahydrobiopterin (BH4), a cofactor of nitric oxide (NO) synthase, attenuates gastric ischemia-reperfusion injury induced by clamping of the celiac artery. Gastric injury was assessed by a formation of gastric mucosal erosions. The gastric injury was observed at 30 and 60 min after reperfusion following 30-min ischemia and was reduced by superoxide dismutase (SOD), catalase, or NO synthase inhibitors. Therefore, reactive oxygen species (ROS) and NO seem to be implicated in the ischemia-reperfusion injury. Treatment with BH4 reduced the ischemia-reperfusion injury. Pretreatment with sepiapterin, a precursor of BH4, also reduced the ischemia-reperfusion injury with an increase in BH4 content in serum and stomach. Both the increase in BH4 content and the protective effect of sepiapterin were prevented of pretreatment with N-acetylserotonin, an inhibitor of BH4 synthesis. These results suggest that the increase in BH4 content may protect against gastric ischemia-reperfusion injury via reduction of ROS and/or NO toxicity. BH4 might be useful as a therapeutic agent for gastric ischemia-reperfusion injury.

Background: Despite a range of treatment options, about 25% of patients with painful bone metastases suffer from uncontrolled pain. This Phase 3, randomized, double-blind, placebo-controlled trial (24-week treatment/24-week follow-up) examined the efficacy and safety of tanezumab, a monoclonal antibody against nerve growth factor, in subjects with moderate to severe cancer pain due to bone metastasis or multiple myeloma receiving background opioid therapy.Methods: Subjects from 15 countries (Europe, South America, Asia-Pacific regions) were randomized and received double-blind subcutaneous placebo or tanezumab 20 mg at baseline, week 8, and week 16 while continuing optimized opioid therapy. The primary endpoint was change in daily average pain intensity (0 ¼ no pain to 10 ¼ worst possible pain) at the index bone metastasis cancer pain site from baseline to week 8, evaluated via analysis of covariance. Adverse events (AEs) and pre-specified joint safety events (rapidly progressive osteoarthritis [RPOA] type 1 or 2, primary osteonecrosis, subchondral insufficiency fracture, or pathologic fracture; adjudicated by an external expert committee) were also assessed.Results: Tanezumab 20 mg (N ¼72) met the primary endpoint by demonstrating significantly (p ¼ 0.038 with a ¼ 0.048) greater improvement in daily average pain intensity at the index bone metastasis cancer pain site at week 8 compared with placebo (N ¼ 73). LS mean (95% CI) change in pain was -1.25 (-1.94, -0.55) for placebo and -2.03 (-2.73, -1.33) for tanezumab 20 mg. Differences past week 8 were not statistically significant. During the treatment period, the AE profile of tanezumab 20 mg was generally consistent with AEs expected in subjects with cancer pain due to bone metastasis and the known safety profile of tanezumab. The proportion of subjects adjudicated with a pre-specified joint safety event during the study was 0% for placebo and 2.8% for tanezumab 20 mg (pathological fracture near the site of bone metastasis, n ¼ 2). No events of RPOA were reported.Conclusions: Tanezumab 20 mg improved metastatic cancer-related bone pain compared with placebo and the AE profile was generally consistent with previous studies of tanezumab.Clinical trial identification: NCT02609828.