The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of metastatic non-small-cell lung cancer (NSCLC) ...was published in 2016. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Chinese Society of Clinical Oncology (CSCO) to convene a special guidelines meeting immediately after the Chinese Thoracic Oncology Group Annual Meeting 2018, in Guangzhou, China. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic NSCLC cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic NSCLC representing the oncological societies of China (CSCO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the six participating Asian countries. During the review process, the updated ESMO 2018 Clinical Practice Guidelines for metastatic NSCLC were released and were also considered, during the final stages of the development of the Pan-Asian adapted Clinical Practice Guidelines.
To determine the frequency and predictive impact of ROS1 rearrangements on treatment outcomes in never-smoking patients with lung adenocarcinoma.
We concurrently analyzed ROS1 and ALK rearrangements ...and mutations in the epidermal growth factor receptor (EGFR), and KRAS in 208 never smokers with lung adenocarcinoma. ROS1 and ALK rearrangements were identified by fluorescent in situ hybridization.
Of 208 tumors screened, 7 (3.4%) were ROS1 rearranged, and 15 (7.2%) were ALK-rearranged. CD74-ROS1 fusions were identified in two patients using reverse transcriptase–polymerase chain reaction. The frequency of ROS1 rearrangement was 5.7% (6 of 105) among EGFR/KRAS/ALK-negative patients. Patients with ROS1 rearrangement had a higher objective response rate (ORR; 60.0% versus 8.5%; P = 0.01) and a longer median progression-free survival (PFS; not reached versus 3.3 months; P = 0.008) to pemetrexed than those without ROS1/ALK rearrangement. The PFS to EGFR-tyrosine kinase inhibitors in patients harboring ROS1 rearrangement was shorter than those without ROS1/ALK rearrangement (2.5 versus 7.8 months; P = 0.01).
The frequency of ROS1 rearrangements in clinically selected patients is higher than that reported for unselected patients, suggesting that ROS1 rearrangement is a druggable target in East-Asian never smokers with lung adenocarcinoma. Given the different treatment outcomes to conventional therapies and availability of ROS1 inhibitors, identification of ROS1 rearrangement can lead to successful treatment in ROS1-rearranged lung adenocarcinomas.
In the last few decades, the usages of plant sources-based stiff fillers as reinforcement material in polymer composites have attracted significant interests of researchers. The crystalline part of ...the semicrystalline cellulose chains as found in the plant cell walls represents the most highly potential reinforcing agents for polymer. This review systematically covers the extraction of nano-sized cellulose crystals from plant cell wall which involving the applications of several highly effective techniques. The topic about the derivation of products functionality at each stage as well as their influences on the final reinforcing capability is also covered. Apart from these, a detailed overview of current knowledge on the surface modification of nanocellulose has been provided also. Inasmuch, this paper is desired to encourage the emergence of preparation of cellulose derivative nanocrystals with controlled morphology, structure and properties, so that enable positive development of biocompatible, renewable and sustainable reinforcing materials for polymer composites field.
Foods contamination leading to spoilage and growth of pathogenic microorganisms can happen when exposed to environment during slaughtering, processing, packaging and shipping. Although traditional ...food preservation methods such as drying, heating, freezing, fermentation and salting can extend food shelf-life, it is not consummate especially to inhibit the growth of pathogenic microorganisms that may endanger consumers' health. Antimicrobial packaging is a novel development that incorporates antimicrobial agent into polymer film to suppress the activities of targeted microorganisms. However, antimicrobial packaging is still an extremely challenging technology and there are only a few commercialized products found in the market. This review focuses on analyzing the antimicrobial agent development for the past decades till recent technology. The information about performance of antimicrobial packaging such as microbiology performance and physico-mechanical properties of the packaging film were discussed. It is expected such information would provide an overview as well as promote the development of antimicrobial packaging in the food related field and industry.
•Antimicrobial packaging is multifunctional by reducing harmful microbial activity in food.•Antimicrobial packaging helps to increase food safety.•Antimicrobial packaging reduces food wastage and improves food shelf life.•Bio-based antimicrobial agents in packaging provide extra safety for health.
This phase I study evaluated the safety, pharmacokinetics and pharmacodynamics of OPB-51602, a novel oral small-molecule STAT3 inhibitor, in patients with advanced solid tumors. A tolerable dose was ...established; gastrointestinal toxicities and peripheral neuropathy were dose-limiting. Responses observed in EGFR TKI-resistant NSCLC patients suggest anti-tumor activity, warranting further studies.
The aim of this study was to determine the maximum-tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of OPB-51602, an oral, direct signal transduction activator of transcription 3 (STAT3) inhibitor, in patients with refractory solid tumors.
Three cohorts were studied: cohort A, a sequential dose escalation of OPB-51602 administered intermittently (days 1–14 every 21 days); cohort B, an expansion cohort evaluating the dose lower than the MTD; cohort C, evaluating continuous daily dosing.
Fifty-one patients were studied at 2, 4, and 5 mg per day dosing. The MTD was 5 mg; first-cycle dose-limiting toxicities (DLTs) were grade 3 hyponatremia in one patient, and grade 3 dehydration in another. Intermittent dosing of both 2 and 4 mg doses were tolerable, and the recommended phase II dose was 4 mg. Cohort B investigated 4 mg intermittently, whereas cohort C investigated 4 mg continuously. Common toxicities included fatigue, nausea/vomiting, diarrhea, anorexia, and early-onset peripheral neuropathy. Drug-induced pneumonitis occurred in two patients in cohort C. Continuous dosing was associated with a higher incidence of peripheral neuropathy and a lower mean relative dose intensity, compared with intermittent dosing. Steady-state pharmacokinetics was characterized by high oral clearance, mean elimination half-life ranging from 44 to 61 h, and a large terminal-phase volume of distribution. An active metabolite, OPB-51822, accumulated to a greater extent than OPB-51602. Flow cytometry of peripheral blood mononuclear cells demonstrated pSTAT3 (Tyr705) inhibition following exposure. Two patients achieved partial responses at 5 mg intermittently and 4 mg continuously; both had epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with prior EGFR tyrosine kinase inhibitor exposure.
OPB-51602 demonstrates promising antitumor activity, particularly in NSCLC. Its long half-life and poorer tolerability of continuous dosing, compared with intermittent dosing, suggest that less frequent dosing should be explored.
NCT01184807.
A close relationship between inflammation and colon cancer has been widely accepted, and interleukin (IL)-17A plays an important role in controlling colonic inflammation. However, the role of IL-17A ...has not yet been validated in colitis-associated cancer (CAC). This study aims to identify the effects of IL-17A in tumorigenesis utilizing IL-17A-deficient mice in an experimental CAC model. CAC was induced in both the IL-17A-deficient and the C57BL/6 (wild-type, WT) mice by injection of 12.5 mg/kg azoxymethane followed by three rounds of 1.7% dextran sodium sulfate exposure to elicit colitis. On day 63 after the start of the study, mice were sacrificed. Colonic inflammation, proliferation and tumorigenesis were evaluated. Tumor numbers per mouse (1.43 versus 5.80; P = 0.02) and mean tumor size (1.17 versus 3.58 mm; P = 0.01) were significantly decreased in IL-17A-deficient mice compared with WT mice. Furthermore, the inflammation and the proliferation scores of IL-17A-deficient mice were significantly lower than WT mice. In the analysis of inflammatory mediators, IL-6, interferon-γ, tumor necrosis factor-α and IL-17A were markedly decreased in IL-17A-deficient mice compared with WT mice. In the western blot analysis, p-STAT3, cyclin D1, cyclin-dependent kinase 2, cyclin E, Glycogen synthase kinase 3-β and p-Akt were downregulated in IL-17A-deficient mice. Immunohistochemical staining with p-STAT3, Ki-67 and β-catenin revealed lower number of stained cells in IL-17A-deficient mice compared with WT mice. IL-17A ablation significantly decreases CAC tumorigenesis and thus may play an important role associated with chronic colitis.
Considering the promising electrochemical performance of the recently reported pyrophosphate family in lithium ion batteries as well as the increasing importance of sodium ion batteries (SIBs) for ...emerging large‐scale applications, here, the crystal structure, electrochemical properties, and thermal stability of Na2FeP2O7, the first example ever reported in the pyrophosphate family for SIBs, are investigated. Na2FeP2O7 maintains well‐defined channel structures (triclinic framework under the P1 space group) and exhibits a reversible capacity of ≈90 mAh g−1 with good cycling performance. Both quasi‐equilibrium measurements and first‐principles calculations consistently indicate that Na2FeP2O7 undergoes two kinds of reactions over the entire voltage range of 2.0–4.5 V (vs Na/Na+): a single‐phase reaction around 2.5 V and a series of two‐phase reactions in the voltage range of 3.0–3.25 V. Na2FeP2O7 shows excellent thermal stability up to 500 °C, even in the partially desodiated state (NaFeP2O7), which suggests its safe character, a property that is very critical for large‐scale battery applications.
Na2FeP2O7 is reported as the first member in the pyrophosphate family for sodium battery cathodes. Utilizing the well‐defined channel structure, Na2FeP2O7 exhibits a reversible capacity of ≈90 mAh g−1 with several different plateaus corresponding to distinctive Na sites. The thermodynamic and kinetic behaviors of this compound during battery operations are explained well using first principles calculations.
Chemotherapy remains a viable option for the management of advanced non-small-cell lung cancer (NSCLC) despite recent advances in molecular targeted therapy and immunotherapy. We evaluated the ...efficacy of oral 5-fluorouracil-based S-1 as second- or third-line therapy compared with standard docetaxel therapy in patients with advanced NSCLC.
Patients with advanced NSCLC previously treated with≥1 platinum-based therapy were randomized 1 : 1 to docetaxel (60mg/m2 in Japan, 75mg/m2 at all other study sites; day 1 in a 3-week cycle) or S-1 (80–120mg/day, depending on body surface area; days 1–28 in a 6-week cycle). The primary endpoint was overall survival. The non-inferiority margin was a hazard ratio (HR) of 1.2.
A total of 1154 patients (577 in each arm) were enrolled, with balanced patient characteristics between the two arms. Median overall survival was 12.75 and 12.52months in the S-1 and docetaxel arms, respectively HR 0.945; 95% confidence interval (CI) 0.833–1.073; P = 0.3818. The upper limit of 95% CI of HR fell below 1.2, confirming non-inferiority of S-1 to docetaxel. Difference in progression-free survival between treatments was not significant (HR 1.033; 95% CI 0.913–1.168; P = 0.6080). Response rate was 8.3% and 9.9% in the S-1 and docetaxel arms, respectively. Significant improvement was observed in the EORTC QLQ-C30 global health status over time points in the S-1 arm. The most common adverse drug reactions were decreased appetite (50.4%), nausea (36.4%), and diarrhea (35.9%) in the S-1 arm, and neutropenia (54.8%), leukocytopenia (43.9%), and alopecia (46.6%) in the docetaxel arm.
S-1 is equally as efficacious as docetaxel and offers a treatment option for patients with previously treated advanced NSCLC.
Japan Pharmaceutical Information Center, JapicCTI-101155.
While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) ...with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance.
BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs).
Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months interquartile range (IQR): 26.5-37.6 months and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination 15.4 months; 95% confidence interval (CI) 9.2-18.0 months and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), hazard ratio (HR) = 0.96; 95% CI 0.68-1.37. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively.
No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.
•A randomised trial comparing bevacizumab plus osimertinib versus osimertinib alone in EGFR-mutant NSCLC with T790M mutations.•The primary endpoint was investigator-assessed PFS.•No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone.•TRAEs of grade ≥3 were more common in patients on combination than osimertinib alone.
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