Tomohiro Mizuno

OBJECTIVES: Sivelestat sodium hydrate (SSH) may be effective in the early stage of acute respiratory distress syndrome (ARDS) before the neutrophil extracellular trap scaffold structure is complete. Therefore, patients with suppression of fibrinolysis (SF) before the secondary fibrinolytic process might benefit from SSH administration. The primary aim of this study was to determine the effect of the SF state and combination therapy on the effect of SSH administration. METHODS: We retrospectively reviewed the data of patients diagnosed with ARDS at Fujita Health University Hospital between July 2005 and December 2016. Patients with ARDS were stratified into the SF and hyperfibrinolysis (HF) groups. Using the fibrin degradation product (FDP)/D-dimer ratio, cut-off values were set as follows: FDP/D-dimer >2 for the HF group and FDP/D-dimer ≤2 for the SF group. The 28-day mortality was the primary endpoint. RESULTS: In total, 168 patients (71 in the HF group and 97 in the SF group) were included in the analysis. The mortality within 28 days was not different based on SSH administration in either group (HF group: p=0.956, SF group: p=0.957). In the SF group, the mortality rate within 28 days in SSH-treated patients who received antithrombotic drugs was significantly higher than that in patients who received SSH only (p<0.05). However, this finding was not present in the HF group (p=0.786). CONCLUSIONS: Concomitant use of SSH and antithrombotic drugs might worsen the treatment outcome of patients with ADRS in the SF state.

BACKGROUND: Trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) is a standard third-line therapy for unresectable advanced or recurrent colorectal cancer. The standard dosing schedule (5 days of administration followed by 2 days off) is associated with a high incidence of severe neutropenia. Conversely, a biweekly dosing schedule (5 days of administration followed by 9 days off) reportedly reduces this incidence. However, no direct comparison of these regimens has been made. In this study, we retrospectively compared the efficacy and safety of these two dosing schedules. METHODS: We analyzed data from patients who received FTD/TPI + BEV treatment between June 2016 and January 2024 at three hospitals affiliated with Fujita Health University. The effects of the dosing schedules on hematological toxicity, overall survival (OS), and time to treatment failure (TTF) were assessed. RESULTS: Among the 125 patients, 26 and 99 were classified into the standard and biweekly groups, respectively. Grade ≥ 3 neutropenia occurred in 50.0% of patients in the standard group and 29.3% of those in the biweekly group (P = .062), with multivariable analysis confirming the dosing schedule impact (P = .048). Median TTF was 5.4 and 7.0 months, while median OS was 16.4 and 14.5 months (P = .908, 0.947) in the standard and biweekly groups, respectively. CONCLUSION: The biweekly regimen of FTD/TPI + BEV resulted in a lower tendency for severe neutropenia than that in the standard regimen, while maintaining comparable OS and TTF in patients with unresectable advanced or recurrent colorectal cancer.

BACKGROUND: The incidence of chemotherapy-induced nausea and vomiting (CINV) when using an oxaliplatin-based regimen may vary according to the cancer type. This study compared the occurrence of CINV in patients with gastric or colorectal cancers. METHODS: This retrospective study included patients who received oxaliplatin-containing regimens for gastric or colorectal cancer. The incidence of CINV during the first treatment course was evaluated. Propensity score matching (PSM) was performed between gastric cancer (GC) and colorectal cancer (CRC) groups to compare the complete response (CR) and total control (TC) rates as indicators of antiemetic efficacy. The impact of primary tumor resection history, surgical procedure, and antiemetic agents was analyzed in the group with a higher incidence of CINV. RESULTS: The GC group included 99 patients and the CRC group included 180 patients, with 60 patients per group, after PSM. The CR rate was significantly lower in the GC group (75.0%) than in the CRC group (95.0%) (P < 0.01). Before PSM, the TC rate varied significantly by resection type in patients with GC (P = 0.012), indicating that tumor resection influenced the TC rate (P = 0.015). In patients with GC who underwent tumor resection, neither dopamine 2 receptor antagonists (P = 0.090) nor neurokinin 1 receptor antagonist (P = 0.66) use was associated with a significant difference in the CR rate. CONCLUSION: Patients with GC have a higher incidence of CINV than those with CRC. In patients with GC, tumor resection significantly influenced the total control rate of CINV.

BACKGROUND/AIM: Trifluridine/tipiracil (TAS-102) is a standard treatment for unresectable advanced or recurrent colorectal cancer. The incidence of grade 3 or higher neutropenia is high with the standard 5-day-on/2-day-off dosing schedule. Previous studies suggest that a 5-day-on/9-day-off (biweekly) schedule is associated with a lower incidence of neutropenia; however, direct comparative evidence is limited. This study aimed to retrospectively evaluate the impact of TAS-102 dosing schedules on safety. PATIENTS AND METHODS: Patients with colorectal cancer who received TAS-102 with/without bevacizumab with either the standard or biweekly schedule at three Fujita Health University-affiliated hospitals between June 2014 and January 2024 were included. The incidence of neutropenia, anemia, and thrombocytopenia based on the dosing schedule and renal function was retrospectively compared. The effect of dosing schedules on grade ≥3 neutropenia was also evaluated. RESULTS: Among 260 patients, 127 received the standard schedule, and 133 the biweekly schedule. Grade ≥3 neutropenia incidence was significantly lower with the biweekly schedule (26.3%) than with the standard schedule (40.2%) (p=0.0247). Multivariate analysis demonstrated that the standard schedule of TAS-102 was associated with a higher incidence of grade ≥3 neutropenia (p<0.01). Grade ≥3 anemia incidence was also lower with the biweekly schedule (13.5% versus 25.2%) (p=0.0187). Grade ≥3 neutropenia showed a trend towards a higher incidence in patients with estimated glomerular filtration rates ≥60 mL/min, at 29.4% compared with 41.0% in those with rates <60 ml/min (p=0.0679). CONCLUSION: The biweekly schedule of TAS-102 with/without bevacizumab was associated with a significantly lower incidence of grade ≥3 neutropenia than the standard schedule. This schedule may help patients - including those with impaired renal function - adhere to planned treatment regimens.

Objective In 2021, anamorelin, an orally active ghrelin receptor selective antagonist, was approved for the treatment of cachexia in patients with non-small cell lung cancer, gastric cancer, pancreatic cancer, and colon cancer. Cancer cachexia is classified into three stages: pre-cachexia, cachexia, and refractory cachexia, with the pre-cachexia and cachexia stages considered reversible with a combination of nutritional therapy, pharmacotherapy, and exercise therapy. In addition, treatment of cachexia requires early intervention, but diagnosis and early detection of cachexia are difficult. We hypothesized that the initiation of anamorelin treatment may be delayed in clinical practice and explored the appropriate timing of treatment initiation. Methods The data of patients with cachexia who received anamorelin at our hospital from June 2021 to July 2023 were retrospectively reviewed. Anamorelin was administered to 201 patients, of whom 134 were included in the study. Survival time and duration of medication were compared based on the number of objective criteria for anamorelin prescription (C-reactive protein [CRP] >0.5 mg/dL, hemoglobin <12 g/dL, albumin <3.2 g/dL). Multivariate analysis was used to determine the factors associated with continuation of anamorelin treatment for 12 weeks. Results Patients with a higher number of objective criteria for anamorelin prescription (CRP >0.5 mg/dL, hemoglobin <12 g/dL, albumin <3.2 g/dL) had shorter anamorelin treatment duration and survival. In multivariate analysis, 12 weeks of anamorelin treatment was associated with CRP. Comparing CRP ≤0.5 mg/dL vs. CRP >0.5 mg/dL, survival was significantly longer for CRP ≤0.5 mg/dL (p < 0.01). Conclusions Initiating anamorelin treatment with close attention to CRP and ensuring that prescribing criteria are met may be helpful in treating cachexia.