Phase II study of trifluridine/tipiracil (TAS‑102) therapy in elderly patients with colorectal cancer (T‑CORE1401): geriatric assessment tools and plasma drug concentrations as possible predictive biomarkers

Purpose The current study aimed to determine the efficacy of trifluridine/tipiracil for elderly patients with advanced colorectal cancer. Methods This single-arm, open-label, multicenter, phase II study included elderly patients aged 65 years or more who had fluoropyrimidine-refractory advanced colorectal cancer and received trifluridine/tipiracil (70 mg/m2, days 1–5 and 8–12, every 4 weeks). The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), overall response rate (ORR), toxicities, association between efficacy and geriatric assessment scores, and association between toxicity and plasma drug concentrations. Results A total of 30 patients with a mean age of 73 years were enrolled. Median PFS was 2.3 months (95% confidence interval, 1.9–4.3 months), while median OS was 5.7 months (95% confidence interval, 3.7–8.9 months). Patients had an ORR of 0%, with 57% having stable disease. Grade 4 neutropenia was observed in 13% of the patients. Patients with a higher G8 score (15 or more) showed longer PFS than those with a lower G8 score (median 4.6 vs. 2.0 months; p = 0.047). Moreover, patients with grade 3 or 4 neutropenia showed higher maximum trifluridine concentrations than those with grade 1 or 2 neutropenia (mean 2945 vs. 2107 ng/mL; p = 0.036). Discussion The current phase II trial demonstrated that trifluridine/tipiracil was an effective and well-tolerated option for elderly patients with advanced colorectal cancer. Moreover, geriatric assessment tools and/or plasma drug concentration monitoring might be helpful in predicting the efficacy and toxicities in elderly patients receiving this drug. Trial registration number UMIN000017589, 15/May/2015 (The University Hospital Medical Information Network

Decreased circulating branched-chain amino acids are associated with development of Alzheimer’s disease in elderly individuals with mild cognitive impairment

BackgroundNutritional epidemiology has shown that inadequate dietary protein intake is associated with poor brain function in the elderly population. The plasma free amino acid (PFAA) profile reflects nutritional status and may have the potential to predict future changes in cognitive function. Here, we report the results of a 2-year interim analysis of a 3-year longitudinal study following mild cognitive impairment (MCI) participants.MethodIn a multicenter prospective cohort design, MCI participants were recruited, and fasting plasma samples were collected. Based on clinical assessment of cognitive function up to 2 years after blood collection, MCI participants were divided into two groups: remained with MCI or reverted to cognitively normal (“MCI-stable,” N = 87) and converted to Alzheimer’s disease (AD) (“AD-convert,” N = 68). The baseline PFAA profile was compared between the two groups. Stratified analysis based on apolipoprotein E ε4 (APOE ε4) allele possession was also conducted.ResultsPlasma concentrations of all nine essential amino acids (EAAs) were lower in the AD-convert group. Among EAAs, three branched-chain amino acids (BCAAs), valine, leucine and isoleucine, and histidine (His) exhibited significant differences even in the logistic regression model adjusted for potential confounding factors such as age, sex, body mass index (BMI), and APOE ε4 possession (p < 0.05). In the stratified analysis, differences in plasma concentrations of these four EAAs were more pronounced in the APOE ε4-negative group.ConclusionThe PFAA profile, especially decreases in BCAAs and His, is associated with development of AD in MCI participants, and the difference was larger in the APOE ε4-negative population, suggesting that the PFAA profile is an independent risk indicator for AD development. Measuring the PFAA profile may have importance in assessing the risk of AD conversion in the MCI population, possibly reflecting nutritional status.Clinical trial registration[https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025322], identifier [UMIN000021965]

Power efficiency improvement of the composite resonant DC-DC converter

This paper deals with the power efficiency improvement of the composite resonant DC-DC converter, which is developed to be applied to the power conditioner of the photovoltaic generation system. To improve the power efficiency, following three approaches are taken: 1) optimum design of the transformer 2) use of the voltage doubler rectifier. 3) reduction of the winding loss of the transformer. The maximum power efficiency of 98.0% can be realized.1st International Conference on Renewable Energy Research and Applications, ICRERA 2012; Nagasaki; Japan; 11 November 2012 ～ 14 November 201

Novel current resonance DC-DC converter with voltage doubler rectifier for fuel cell system

This paper deals with a novel composite rsonance DC-DC converter for low input voltage, large input current and high output voltsge with the voltage doubler rectifier. which i developed to appl y to the power conditioner of the fuel system. The proposed DC-DC cnverter has the current and voltage resonance fnctions to reduce the switching power loss. The primary and secondary sides of the converter are composed of the current resonant full bridge circuit, and voltage doubler, respectively. For this reason, the high power efficiency of this converter can be realized under the condition of a low input voltage, large iput current and high output voltage.2010 IEEE International Conference on Sustainable Energy Technologies (ICSET) : Kandy, Sri Lanka, 2010.12.6-2010.12.

Novel series resonance DC-DC converter with voltage doubler rectifier

This paper deals with a novel composite resonance DC-DC converter with the voltage doubler rectifier, which is developed to be applied to the power conditioner of the photovoltaic generation system. The proposed DC-DC converter has the current and voltage resonance functions. Therefore, the output voltage regulation can be achieved for the large variations of the input voltage and load. Also, this converter has the high power efficiency. The maximum power efficisncy 97.7% can be realized.2010 IEEE International Conference on Sustainable Energy Technologies (ICSET) : Kandy, Sri Lanka, 2010.12.6-2010.12.

Novel composite resonance DC-DC converter with voltage doubler rectifier

This paper deals with a novel composite resonance DC-DC converter with the voltage doubler rectifier, which is developed to be applied to the power conditioner of the photovoltaic generation system. The proposed DC-DC converter has the current and voltage resonance functions. Therefore, the output voltage regulation can be achieved for the large variations of the input voltage and load. Also, this converter has the high power efficiency. The maximum power efficiency 96.1% can be realized.INTELEC 2009 - 2009 International Telecommunications Energy Conference : Incheon, South Korea, 2009.10.18-2009.10.2