Single-Drug Approach with Edoxaban is Effective for Resolving Non-Acute Cancer-Associated Venous Thrombosis: A Single-Arm Retrospective Analysis.

Recently, cancer-related venous thromboembolism (VTE) has been termed "cancer-associated thrombosis (CAT)" and is the focus of current research. We retrospectively investigated the efficacy of a single-drug approach with edoxaban for the treatment of non-acute CAT. Thirty-two non-acute CAT patients who received edoxaban were analyzed. The primary endpoint of this analysis was the thrombus disappearance rate at the first evaluation. Secondary endpoints included progression/recurrence of VTE, major bleeding, and D-dimer levels. The thrombus disappearance rate was 62.5%. Therefore, the null hypothesis for the primary endpoint (thrombus disappearance rate of ≤32.0%) was rejected (p = 0.00038) based on the rate of the previous study as the historical control. Recurrent VTE and major bleeding occurred in two patients each. After the start of treatment with edoxaban, a significant difference in D-dimer levels was observed (p = 0.00655). We demonstrated that a single-drug approach with edoxaban is a potential treatment option for non-acute CAT.

Variants of carboxylesterase 1 have no impact on capecitabine pharmacokinetics and toxicity in capecitabine plus oxaliplatin treated-colorectal cancer patients.

PURPOSE: Capecitabine is a prodrug that undergoes metabolism in three steps to form an active 5-fluorouracil (5-FU). The first step is primarily catalyzed by liver carboxylesterases (CES) 1. Here, we examined the effects of CES1 variants on pharmacokinetics and toxicity of capecitabine. METHODS: We enrolled postoperative colorectal cancer (CRC) patients administered with adjuvant capecitabine plus oxaliplatin (CapeOX) and metastatic CRC patients receiving CapeOX. The pharmacokinetic analysis of the first capecitabine dose (1000 mg/m2) was done on day 1, and oxaliplatin administration was shifted to day 2. Plasma concentrations of capecitabine, 5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine (5'-DFUR), and 5-FU were analyzed by high-performance liquid chromatography. CES1 polymorphisms (rs3217164, rs2244614, rs2244613, rs7187684, and rs11861118) and the functional CES1 genes (1A1, var1A1, 1A2, and pseudo 1A3) in their diplotype configurations were analyzed by direct sequencing. RESULTS: Thirty-seven patients were enrolled from September 2017 to February 2020. Patients with a higher area under the plasma concentration-time curve to capecitabine dose ratio (AUC/dose) of 5'-DFUR than its mean showed a higher frequency of overall ≥ grade 3 toxicity and lower relative dose intensity (RDI) of capecitabine than those with a lower ratio. Higher CES1 activity expressed as a metabolic ratio (AUC of capecitabine/sum of three AUCs of each metabolite) lower than its mean was associated with higher 5'-DFUR AUC/dose and lower RDI, indicating essential roles of CES1 in capecitabine activation to produce 5'-DFUR. However, the association between CES1 variants and capecitabine pharmacokinetics and toxicity was not significant. CONCLUSION: CES1 variants are not associated with capecitabine pharmacokinetics and toxicity.

VEGF Inhibitors Do Not Increase D-dimer Levels in Colorectal Cancer Patients Without Venous Thromboembolism: A Retrospective Non-inferiority Analysis

BACKGROUND/AIM: If VEGF inhibitors contribute to an increase in D-dimer levels, they may adversely affect the diagnosis of venous thromboembolism (VTE). Consequently, this retrospective study examined the effects of VEGF inhibitors on D-dimer levels in colorectal cancer patients. PATIENTS AND METHODS: A total of 104 colorectal cancer patients who received chemotherapy, were included in this study. To perform D-dimer analysis, patients were divided into two analysis targets: patients with VTE and without VTE. Statistical analysis included a natural logarithmic transformation of D-dimer data. RESULTS: In the D-dimer analysis of non-VTE patients, the natural logarithm D-dimer mean difference was -0.186, with a 95% CI of -0.525 to 0.154. The upper limit of the 95%CI (0.154) did not exceed the non-inferiority margin (Δ) of 0.199, and therefore met the non-inferiority criteria. CONCLUSION: VEGF inhibitors don't contribute to increased D-dimer levels in colorectal cancer patients without VTE.

Two cases of lymphangitic carcinomatosis as the primary symptom of colorectal carcinoma that achieved complete remission using combination anti-EGFR antibody therapy.

Clinicians often encounter cases of pulmonary lymphangitic carcinomatosis when treating patients with cancer. When such a condition develops before the diagnosis of cancer, its diagnosis is often challenging. Herein, we report about two patients with colorectal carcinoma diagnosed after the identification of lymphangitic carcinomatosis, which achieved complete remission with combination anti-epidermal growth factor receptor (anti-EGFR) antibody therapy. In case 1, a 74-year-old woman presented with cough and dyspnea that had persisted for 1 month. She had unresectable advanced carcinoma of the sigmoid colon with lymphangitic carcinomatosis. Her respiratory status gradually deteriorated due to the disease. Thus, FOLFIRI plus cetuximab therapy was initiated. Her dyspnea rapidly resolved with the treatment, and complete remission of lymphangitic carcinomatosis was achieved. In case 2, a 46-year-old man presented with fever and dyspnea that had persisted for 1 month. He had unresectable advanced carcinoma of the transverse colon with lymphangitic carcinomatosis. FOLFOXIRI therapy was then initiated. However, his respiratory status did not improve. Therefore, his treatment was immediately switched to FOLFIRI plus panitumumab. His dyspnea rapidly resolved with the treatment, and complete remission of lymphangitic carcinomatosis was achieved. In oncologic emergencies, such as lymphangitic carcinomatosis, requiring an early response to treatment, the administration of anti-EGFR antibodies may be a highly effective treatment option.

Early tumor shrinkage as a predictor of favorable outcomes in patients with advanced pancreatic cancer treated with FOLFIRINOX.

There are several reports on the correlation between early tumor shrinkage (ETS) or depth of response (DpR) and survival in chemotherapies for colorectal cancer; however, few studies have investigated it in pancreatic cancer. We therefore investigated whether the ETS will predict outcomes in 59 patients with advanced pancreatic cancer treated with FOLFIRINOX therapy. The association of ETS with progression-free survival (PFS) and overall survival (OS) was evaluated but also we addressed to the correlation between outcomes and DpR. ETS was defined as a reduction ≥ 20% of target lesions' diameters measured at 6 to 8 weeks from treatment start. DpR was percentage of maximal tumor shrinkage observed at the nadir diameter compared with baseline. Among 47 evaluable patients for the ETS, 12 (25.5%) patients experienced ETS. The ETS was significantly associated with better PFS (9.0 vs. 4.2 months) as well as OS (24.0 vs. 9.1 months); moreover, the association had a statistically significance for PFS but a strong trend for OS in multivariate analysis. The DpR was statistically significantly but weakly associated with OS. In conclusion, this is the first report that the early response to chemotherapy may predict favorable outcomes in patients with advanced pancreatic cancer treated with FOLFIRINOX therapy.

[A Case of HER2-Positive Esophagogastric Junction Cancer with Perforation Curatively Resected after Neoadjuvant Chemotherapy plus Trastuzumab].

A 60-year-old man was diagnosed with adenocarcinoma of the esophagogastric junction with lymph node metastasis along the left gastric artery. The clinical stage was determined to be T4b, N1, M0, Stage IIIB, and a neoadjuvant chemotherapy (NAC)regimen of capecitabine/CDDP plus trastuzumab was selected for treatment. Before 3 courses of chemotherapy, the patient developed perforated gastric cancer. With conservative therapy, we were able to obtain closure of the perforation without affecting the curability of the cancer. We changed the chemotherapy regimen to S-1/CDDP plus trastuzumab, and the patient underwent curative resection.

The effect of long-running severe selenium-deficiency on the amount of iron and zinc in the organs of rats.

The amounts of selenium (Se), iron (Fe), and zinc (Zn) in the liver, kidney, and spleen as a function of age of rats measured using instrumental neutron activation analysis were compared between Se-deficient (SeD) rats and normal rats. The SeD model rats can live for more than 50 weeks. The effect of Se-deficinecy in rats might be weak, compared to the marked malfunction of GSH-Px. The SeD rats can be considered as a model of nonlethal chronic oxidative stress. Fluctuations of Fe and Zn in the liver of Se-deficient rats were observed. The amount of redox-relating minerals, such as Fe and Zn, in SeD rat organs is changeable depending on the age.

Electron paramagnetic resonance decay constant and oxidative stresses in liver microsomes of the selenium-deficient rat.

The free radical-reducing activity and the membrane fluidity of liver microsomes from selenium-deficient (SeD) rats were examined by means of electron paramagnetic resonance (EPR) spin label method using nitroxyl-labeled stearic acids. Our findings show that the membrane fluidity and lipid peroxidation levels in SeD rat liver microsome were relatively unchanged compared with normal rat. In contrast, SeD caused the induction of liver microsomal cytochrome P-450 activity. The nitroxyl spin probes are substrates for reduction-relating cytochrome P-450. Previous in vivo studies suggested that the total liver free radical reduction activity in SeD rat was decreased. In contrast, SeD caused the induction of liver microsomal cytochrome P-450 activity, and the reduction rate of nitroxyl radical existing at shallow depth in membrane was increased. Selenium-deficient rats experienced an increase in hydrogen peroxide (H2O2) due to a pronounced loss of glutathione peroxidase (GSH-Px) activity. This masked the overall reduction rate of the nitroxyl spin probe by reoxidation of the hydroxylamine form. Although the SeD condition caused induction of liver cytochrome P-450 and chronic increased H2O2, this did not result in oxidative liver damage. An increased level of glutathione in SeD liver was also evident, likely due to the absence of GSH-Px activity. Using the EPR spin label method, we have shown that SeD causes complicated redox changes in the liver, notably, alterations in the levels of cytochrome P-450 and GSH-Px systems.