Explore the vast range of titles available.

Carbon dioxide (CO 2 ) is one of the most important materials as renewable chemical feedstock. In this review, the Co- and Rh-catalyzed transformation of CO 2 via carbon–carbon bond-forming reactions is summarized. Combinations of metals (cobalt or rhodium), substrates, and reducing agents realize efficient carboxylation reactions using CO 2 . The carboxylation of propargyl acetates and alkenyl triflates using cobalt complexes as well as the cobalt-catalyzed reductive carboxylation of α,β-unsaturated nitriles and carboxyamides in the presence of Et 2 Zn proceed. A Co complex has been demonstrated to act as an efficient catalyst in the carboxylation of allylic C(sp 3 )–H bonds. Employing zinc as the reductant, carboxyzincation and the four-component coupling reaction between alkyne, acrylates, CO 2 , and zinc occur efficiently. Rh complexes also catalyze the carboxylation of arylboronic esters, C(sp 2 )–H carboxylation of aromatic compounds, and hydrocarboxylation of styrene derivatives. The Rh-catalyzed [2 + 2 + 2] cycloaddition of diynes and CO 2 proceeds to afford pyrones.

Surgical resection is currently the best curative approach for gastric cancer (GC); however, the prognosis of patients with advanced GC remains poor even with curative resection. For this reason, perioperative chemotherapy has been combined with surgery to reduce the risk of postoperative recurrence. Standard perioperative chemotherapy for resectable advanced GC varies from region to region. Postoperative S-1 therapy was standardized via the ACTS-GC study in East Asia, perioperative ECF (Epirubicin + Cisplatin + Fluorouracil) was standardized via the MAGIC study in Europe, and postoperative chemoradiotherapy was standardized via the US intergroup study in North America. Since then, more intensive regimens have been developed. In recent years, perioperative therapy using novel agents, such as molecular-targeted drugs and immune checkpoint inhibitors (ICIs), has also been tested and evaluated in the three major regions (East Asia, Europe, and North America) with promising results. Perioperative chemotherapy has become an integral part of many treatment strategies and requires continued research and evaluation.

Biological systems are known to spontaneously adjust the functioning of neurotransmitters, ion channels, and the immune system, being promoted or regulated through allosteric effects or inhibitors, affording non-linear responses to external stimuli. Here we report that an insulated conjugated bimetallopolymer, in which Ru(II) and Pt(II) complexes are mutually connected with insulated conjugations, exhibits phosphorescence in response to CO gas. The net profile corresponds to a sigmoidal response with a dual self-controlling system, where drastic changes were exhibited at two threshold concentrations. The first threshold for activation of the system is triggered by the depolymerization of the non-radiative conjugated polymer to luminescent monomers, while the second one for regulation is triggered by the switch in the rate-determining step of the Ru complex. Such a molecular design with cooperative multiple transition metals would provide routes for the development of higher-ordered artificial molecular systems bearing bioinspired responses with autonomous modulation. Molecules can serve as biomimetic sensors, but dual self-controlling systems that involve self-activation and self-regulation are difficult to mimic. Here the authors report an insulated conjugated bimetallopolymer with cooperative multiple transition metals that phosphoresces in response to carbon monoxide.

Treatments that confer survival benefit are needed in patients with heavily pretreated metastatic colorectal cancer. The aim of this trial was to investigate the efficacy and safety of TAS-102—a novel oral nucleoside antitumour agent. Between August 25, 2009, and April 12, 2010, we undertook a multicentre, double-blind, randomised, placebo-controlled phase 2 trial in Japan. Eligible patients were 20 years or older; had confirmed colorectal adenocarcinoma; had a treatment history of two or more regimens of standard chemotherapy; and were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin. Patients had to be able to take oral drugs; have measurable lesions; have an Eastern Cooperative Oncology Group performance status of between 0 and 2; and have adequate bone-marrow, hepatic, and renal functions within 7 days of enrolment. Patients were randomly assigned (2:1) to either TAS-102 (35 mg/m2 given orally twice a day in a 28-day cycle [2-week cycle of 5 days of treatment followed by a 2-day rest period, and then a 14-day rest period]) or placebo; all patients received best supportive care. Randomisation was done with minimisation methods, with performance status as the allocation factor. The randomisation sequence was generated with a validated computer system by an independent team from the trial sponsor. Investigators, patients, data analysts, and the trial sponsor were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. Safety analyses were done in the per-protocol population. The study is in progress and is registered with Japan Pharmaceutical Information Center, number JapicCTI-090880. 112 patients allocated to TAS-102 and 57 allocated to placebo made up the intention-to-treat population. Median follow-up was 11·3 months (IQR 10·7–14·0). Median overall survival was 9·0 months (95% CI 7·3–11·3) in the TAS-102 group and 6·6 months (4·9–8·0) in the placebo group (hazard ratio for death 0·56, 80% CI 0·44–0·71, 95% CI 0·39–0·81; p=0·0011). 57 (50%) of 113 patients given TAS-102 in the safety population had neutropenia of grade 3 or 4, 32 (28%) leucopenia, and 19 (17%) anaemia. No patient given placebo had grade 3 or worse neutropenia or leucopenia; three (5%) of 57 had grade 3 or worse anaemia. Serious adverse events occurred in 21 (19%) patients in the TAS-102 group and in five (9%) in the placebo group. No treatment-related deaths occurred. TAS-102 has promising efficacy and a manageable safety profile in patients with metastatic colorectal cancer who are refractory or intolerant to standard chemotherapies. Taiho Pharmaceutical.

Summary Purpose NK105 is a new drug delivery system formulation for paclitaxel (PTX) whose recommended dose (RD)　is 150 mg PTX equivalent/m 2 administered every 3 weeks, as determined in a phase I trial. This study aimed to evaluate the efficacy and safety of NK105 in patients with advanced gastric cancer after failure of first-line chemotherapy. Experimental design Eligible patients had measurable disease and one chemotherapeutic regimen except taxane. NK105 (150 mg PTX equivalent/m 2 ) was administered by a 30-minute intravenous infusion every 3 weeks without anti-allergic premedication until disease progression, unacceptable toxicity or patient refusal. The primary efficacy endpoint was best overall response rate (ORR) post baseline. The secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF) and overall survival (OS). All adverse events were reported using CTCAE v3.0. Results Between November 2007 and July 2009, 57 patients were enrolled and 56 were evaluable for efficacy. Two complete responses and 12 partial responses were observed for an ORR of 25%. The median PFS was 3.0 months, the median TTF was 2.8 months, and the median OS was 14.4 months. Drug related toxicity was mainly mild (grades 1–2) to severe (grades 3–4); other data: neutropenia (64.9%); leukopenia (17.5%); lymphopenia (8.8%); neuropathy-sensory (1.8%); fatigue (3.5%); and stomatitis (1.8%). There were no treatment-related deaths. Conclusions This study of NK105 (150 mg PTX equivalent/m 2 ) proves the concept for the modest activity and tolerability of a new drug delivery system formulation for PTX. A phase III trial will be evaluated to clarify survival benefit.

In the Original publication of the article, the authors found an error in the “Results” section under the heading “Abstract”. The corrected text is given below.

Background Among patients with colorectal cancer (CRC) treated with oxaliplatin (L-OHP)-based chemotherapy, delayed chemotherapy-induced nausea and vomiting (CINV) have not been well controlled. Methods We pooled data from two prospective observational studies in Japan and one phase III clinical trial to assess whether delayed CINV could be controlled with a combination of three antiemetics adding a neurokinin-1 receptor antagonist and identified individual risk factors, using an inverse probability treatment-weighted analysis. Results A total of 661 patients were evaluable in this study (median age: 64 years; 391 male, and 270 female). 3 antiemetics controlled delayed nausea (33.18% vs. 42.25%; p  = 0.0510) and vomiting (4.15% vs. 16.08%; p  < 0.0001) better than with 2 antiemetics. Female and 2 antiemetics were risk factors for both delayed nausea (female—odds ratio [OR]: 1.918; 95% confidence interval [CI]: 1.292–2.848; p  = 0.0012; 2 antiemetics—OR: 1.485; 95% CI: 1.000–2.204; p  = 0.0498) and delayed vomiting (female—OR: 2.735; 95% CI: 1.410–5.304; p  = 0.0029; 2 antiemetics—OR: 4.551; 95% CI: 2.116–9.785; p  = 0.0001). Conclusions Identifying individual risk factors can facilitate personalized treatments for delayed CINV. We recommend a 3-antiemetic combination prophylaxis for CRC patients treated with L-OHP-based chemotherapy, especially for female patients.

PurposeThe current study aimed to determine the efficacy of trifluridine/tipiracil for elderly patients with advanced colorectal cancer.MethodsThis 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.ResultsA 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).DiscussionThe 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 numberUMIN000017589, 15/May/2015 (The University Hospital Medical Information Network)

Background Although Asian population was recognized to have a lower risk of venous thromboembolism (VTE), its increasing prevalence and incidence remain unclear in patients with malignancies. We attempted to predict VTE development using activation markers of coagulation and fibrinolysis. Methods We enrolled patients with malignancy admitted to Tonan Hospital between April and December 2014 to receive a new-for-them chemotherapy regimen. All patients were examined for VTE by computed tomography and whole-leg compression ultrasonography before chemotherapy and three months later. We also examined plasma levels of thrombin-antithrombin complex (TAT) and plasmin α2-plasmin inhibitor complex (PIC) before chemotherapy. The cut off values of TAT and PIC were set at 2.1 ng/mL and 1.8 μg/mL, respectively. Results Of 97 patients, the majority (67%) had distant metastases. The most common malignancies were colorectal (26%), breast (23%), and stomach (19%) cancer. VTE was detected in 29 patients (31%); all were asymptomatic. VTE was newly developed in 12 patients in the three-month observation period, which means the incidence was 49 per 1000 person-years. Non-increased PIC with increased TAT was the only significant risk factor for both VTE prevalence and incidence in multivariate analysis, and the odds ratios were 3.0 (95% confidence interval, 1.1–8.2; P  = 0.034) and 9.4 (95% confidence interval, 1.7–51.9; P  = 0.011), respectively. Conclusions The prevalence and incidence of VTE were high in hospitalized Japanese patients receiving chemotherapy for malignancies. Non-increased PIC with increased levels of TAT may be an independent risk factor for VTE development.

Cisplatin plus 5‐fluorouracil is regarded as standard neoadjuvant chemotherapy for esophageal squamous cell carcinoma (ESCC) in Japan, but the prognosis remains poor. We have previously described how definitive chemoradiotherapy with docetaxel, nedaplatin, and 5‐fluorouracil (DNF) led to a very high response rate and promising survival times. We therefore undertook a phase II trial to evaluate the feasibility and efficacy of neoadjuvant DNF. The study included patients with clinical stage Ib‐III ESCC. Chemotherapy consisted of i.v. docetaxel (30 mg/m2) and nedaplatin (50 mg/m2) on days 1 and 8, and a continuous infusion of 5‐fluorouracil (400 mg/m2/day) on days 1‐5 and 8‐12, every 3 weeks. After three courses of chemotherapy, esophagectomy was carried out. The primary end‐point was the completion rate of the protocol treatment. Twenty‐eight patients were enrolled (cStage Ib/II/III, 2/3/23) and all received at least two cycles of chemotherapy. Twenty‐five patients underwent surgery, all of whom achieved an R0 resection, leading to a completion rate of 89.3%. The overall response rate was 87.0%. A pathological complete response was confirmed in eight (32.0%) cases. Grade 3/4 adverse events included leukopenia (32.1%), neutropenia (39.3%), febrile neutropenia (10.7%), thrombocytopenia (10.7%), and diarrhea (14.3%), but were manageable. Treatment‐related deaths and major surgical complications did not occur. Estimated 2‐year progression‐free and overall survival rates were 70.4% and 77.2%, respectively. Thus, DNF therapy was well tolerated and deemed feasible, with a strong tumor response in a neoadjuvant setting for ESCC. This trial is registered with the University Hospital Medical Information Network (UMIN ID: 000014305). This phase II study investigated a regimen of neoadjuvant chemotherapy for resectable esophageal squamous cell carcinoma using docetaxel, nedaplatin, and 5‐fluorouracil (DNF), which indicated that DNF was well tolerated and effective. A completion rate for protocol treatment was 89.3%, and all patients who underwent surgery achieved an R0 resection. The overall response rate was 87.0%, with a pathological complete response rate of 32.0%. The 2‐year survival rate was 77.2%.