安藤 洋介

BACKGROUND/AIM: We previously reported that benzodiazepines with anticholinergic effects are a risk factor for infection in patients with diffuse large B-cell lymphoma; however, the effects of other anticholinergic drugs and the trend of severe infections, such as febrile neutropenia (FN), have not been investigated. The Japanese Anticholinergic Risk Scale (JARS) was developed by the Japanese Society of Geriatric Pharmacy to screen for potentially inappropriate medications with anticholinergic effects. This study aimed to elucidate the trend of FN induced by anticancer chemotherapy in patients who received anticholinergic drugs listed in the JARS. PATIENTS AND METHODS: We obtained data from the JADER. Reporting odds ratios (RORs) were used to detect safety signals for FN. Anticholinergic drugs were classified into three categories according to their JARS score. Safety signals for FN were considered positive if the lower limit of the 95% confidence interval (CI) of the ROR was >1. RESULTS: A total of 162,918 cases were included in the dataset. RORs for FN indicated that cases with an anticholinergic risk score of 1 and 3 showed a safety signal (score 1: ROR=1.748, 95%CI=1.659-1.841; score 3: ROR=1.525, 95%CI=1.371-1.696), while no safety signals were observed for those with a risk score of 2 (ROR=1.015, 95%CI=0.863-1.194). Similar trends were observed in cases 70 years old and over and those under 70 years old. CONCLUSION: The trend of FN in patients who received an anticholinergic drug listed in the JARS was similar among younger and older patients.

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.

PURPOSE: Although the efficacy of trifluridine/tipiracil hydrochloride (TAS-102) in treating metastatic colorectal cancer (mCRC) is well established, its non-hematologic toxicities in relation to renal function remain unclear. This study aimed to assess the impact of creatinine clearance (Ccr) on non-hematologic toxicities, including nausea and vomiting, in patients with mCRC treated with TAS-102. METHODS: This study was conducted as a post-hoc analysis of the JASCC-CINV2001 study, a multicenter observational study of mCRC patients. Using a Cox proportional hazards model, we assessed the relationship between Ccr and nausea or vomiting, and used a generalized estimating equations (GEE) logistic regression model to analyze the association between Ccr and additional toxicities, including fatigue, constipation, diarrhea, insomnia, and dysgeusia. Toxicities were evaluated at weekly intervals over four weeks. RESULTS: Among 100 patients, median Ccr was 80.5 ml/min. The primary analysis showed no significant association between Ccr and nausea or vomiting. However, the secondary analysis revealed a significant link between lower Ccr and the incidence of diarrhea (P = 0.02). CONCLUSION: These results suggest that although TAS-102-induced nausea and vomiting are not strongly influenced by renal function, decreased renal function increases the risk of diarrhea. Enhanced antiemetic measures may not be necessary for TAS-102 patients with impaired renal function, but monitoring for diarrhea is recommended.

BACKGROUND: Outpatient chemotherapy is a standard treatment for cancer. In nursing care for outpatients, it is important to enhance patients' self-efficacy. Vicarious experiences that can be gained through interactions with other patients with cancer can be useful for achieving this. While inpatients can gain vicarious experiences through their hospital stay, outpatients typically have fewer opportunities to do so. AIMS: This report aimed to examine the results of implementation of support meetings for patients receiving outpatient chemotherapy. METHODS: Starting in April 2019, support meetings were held once a month for outpatients on Thursdays from 14:00 to 16:00 in a hospital conference room. Medical professionals designed the programme of support meetings to allow patients to interact with each other and engage in vicarious experiences. At each meeting, satisfaction regarding the support meeting content was evaluated by self-administered questionnaire. Moreover, the nurse asked all participants to talk about their interactions, and recorded and extracted narratives about vicarious experiences. FINDINGS: The 32 participants had a median age (interquartile range) of 63.5 years (55-70 years). There were 26 females (81.2%). The median satisfaction scores ranged from 2.9 to 4 for the content of each meeting. Patients talked about the value of learning from the experiences of other patients and the easing of loneliness. CONCLUSION: The results suggested that support meetings can provide vicarious experiences for patients receiving outpatient chemotherapy.

BACKGROUND/AIM: The frequency rate of injection site reactions (ISR) due to fosaprepitant meglumine (Fos APR) has been shown to vary depending on the types of combined anticancer drug. This study aimed to elucidate the impact of Fos APR on ISR in patients receiving paclitaxel and carboplatin, with and without bevacizumab therapy (TC±Bev). PATIENTS AND METHODS: This study focused on patients with gynecologic cancer (n=93) who received TC±Bev administration at Fujita Health University Hospital from March 2016 to February 2020, and monitored up to six cycles. The patients were randomly assigned to the Fos APR group (n=47) and the Aprepitant (APR) group (n=46). Using Visual Infusion Phlebitis (VIP) scores, ISR was evaluated by comparing the VIP scores of all cycles using a linear mixed model. The risk factors that contribute to the occurrence of vascular pain throughout all cycles were also examined. RESULTS: The VIP scores of all cycles showed a near significant intergroup difference (p=0.071). Factors that affected the development of vascular pain included Fos APR and age (p=0.027 and 0.049, respectively). Regarding age, patients aged <65 years had a higher risk. Four patients underwent a switch from the originally assigned neurokinin-1 receptor antagonist; in all of these cases, Fos APR was changed to APR for vascular pain. CONCLUSION: Fos APR may increase the risk for ISR associated with TC±Bev therapy for gynecological cancer.

BACKGROUND: Chemotherapy-induced thrombocytopenia is often a use-limiting adverse reaction to gemcitabine and cisplatin (GC) combination chemotherapy, reducing therapeutic intensity, and, in some cases, requiring platelet transfusion. OBJECTIVE: A retrospective cohort study was conducted on patients with urothelial cancer at the initiation of GC combination therapy and the objective was to develop a prediction model for the incidence of severe thrombocytopenia using machine learning. METHODS: We performed receiver operating characteristic analysis to determine the cut-off values of the associated factors. Multivariate analyses were conducted to identify risk factors associated with the occurrence of severe thrombocytopenia. The prediction model was constructed from an ensemble model and gradient-boosted decision trees to estimate the risk of an outcome using the risk factors associated with the occurrence of severe thrombocytopenia. RESULTS: Of 186 patients included in this study, 46 (25%) experienced severe thrombocytopenia induced by GC therapy. Multivariate analyses revealed that platelet count ≤ 21.4 (×104/µL) [odds ratio 7.19, p < 0.01], hemoglobin ≤ 12.1 (g/dL) [odds ratio 2.41, p = 0.03], lymphocyte count ≤ 1.458 (×103/µL) [odds ratio 2.47, p = 0.02], and dose of gemcitabine ≥ 775.245 (mg/m2) [odds ratio 4.00, p < 0.01] were risk factors of severe thrombocytopenia. The performance of the prediction model using these associated factors was high (area under the curve 0.76, accuracy 0.82, precision 0.68, recall 0.50, and F-measure 0.58). CONCLUSIONS: Platelet count, hemoglobin level, lymphocyte count, and gemcitabine dose contributed to the development of a novel prediction model to identify the incidence of GC-induced severe thrombocytopenia.

BACKGROUND/AIM: Renal dysfunction necessitates S-1 dose reduction. However, decreased dihydropyrimidine dehydrogenase (DPD) activity may lead to adverse events due to 5-FU. The guidelines provided by pharmaceutical companies state that total bilirubin (T-Bil) should be ≤upper limit of normal (ULN)×1.5 as a reference value for safely taking S-1. Nevertheless, the relationship between the degree of liver dysfunction and S-1 dose reduction has not been clearly established. PATIENTS AND METHODS: This study focused on patients who received S-1 monotherapy for various types of cancer. The primary outcome was defined as the variation between blood sampling results on the test day and the subsequent test. The variation data were categorized based on the difference in T-Bil: Low T-Bil group (≤2.25) and High T-Bil group (>2.25). RESULTS: The number of patients that underwent S-1 monotherapy was 883 and the running number was 7,511; Low T-Bil group included 7,245 and High T-Bil group included 266. Examination of the effect of the T-Bil Group on clinical outcomes revealed a correlation with red blood cell (RBC) count, platelet (PLT) count, and T-Bil level. When the impact of the interaction between the T-Bil Group and any of the clinical outcomes, such as the RBC count, PLT count, and T-Bil level, was determined, each outcome showed a significant decrease in the High T-Bil group compared with the Low T-Bil group. CONCLUSION: S-1 administration in patients with liver dysfunction accompanied by elevated T-Bil levels may cause thrombocytopenia.

Pharmaceutical consultation targeting outpatients at the Fujita Health University Hospital (Japan) provides support to patients undergoing anticancer drug treatment. This study aimed to explore factors that affect the comprehension of cancer chemotherapy among outpatients who received cancer treatment at our hospital. A questionnaire survey was conducted, and comprehension was scored on a scale of 1-5 (1, no comprehension; 5, full comprehension). When factors other than age and sex [the influence of which on comprehension has been reported in previous reports] were noted, differences in comprehension between the questionnaire items were comparatively analyzed according to the presence/absence of the relevant factors. Overall, 536 patients were included. Age (<70 years) and pharmacist interventions were identified as factors contributing to a comprehension score. The levels of comprehension regarding the name of the cancer chemotherapy, content/schedule of the treatment, purposes of the prescribed drugs, and objectives of blood tests were significantly higher in the group that received the pharmaceutical interventions; conversely, the level of comprehension for the self-management of adverse events was significantly lower in this group than in the group that did not receive any pharmaceutical interventions. Age and interventions by the pharmacist affected the comprehension of cancer chemotherapy by patients.

OBJECTIVES: Zinc (Zn) is a cofactor for more than 200 enzymes within the human body. Zn deficiency can result in cell-mediated immune dysfunction. Furthermore, serum Zn levels have been reported to be associated with nutritional status, but this association has not been clarified in malignant lymphoma. This study aimed to examine the deficiency of serum Zn levels and clarify the factors that are correlated with serum Zn in malignant lymphoma. METHODS: Initial malignant lymphoma was diagnosed in patients at Fujita Health University Hospital between April 2011 and March 2019. Based on the serum Zn levels, the study population was divided into "deficient" and "low or normal". For the serum Zn levels of patients undergoing pre-chemotherapy, laboratory parameters and nutritional factors were included. We compared these factors between the abovementioned two groups, and the serum Zn levels with its correlation factors were investigated. RESULTS: A total of 77 patients (Deficient group, n=20 and Low or Normal group, n=57) were enrolled. Histology, hemoglobin, serum albumin levels, Glasgow Prognostic Score (GPS), neutrophile-lymphocyte ratio (NLR), prognostic nutrition index (PNI) and Controlling Nutritional Status (CONUT) were significantly different between the two groups. Of these parameters, only serum albumin level was significantly associated with serum Zn level (p=0.0024; estimated regression coefficient, 9.51; adjusted coefficient of determination, 0.28). CONCLUSIONS: Poor nutritional status at the initial diagnosis may have affected Zn deficiency in initial malignant lymphoma.

BACKGROUND/AIM: Early palliative care (EPC) intervention in patients with solid tumors can provide many benefits. However, studies on patients with hematological malignancies are limited, and there is no data on patients with lymphoma. We conducted a preliminary retrospective survey of palliative care (PC) intervention in patients with lymphoma to clarify the effect of EPC on overall survival (OS). PATIENTS AND METHODS: The first palliative care consultation (PC1) was retrospectively reviewed from medical records in Japan. Patients with lymphoma requiring inpatient PC at our institution from January 2012 to December 2018 were recruited. We conducted receiver operating characteristic (ROC) analysis; patients were divided into two groups (early and delayed), and the survival periods and palliative care team (PCT) referral details were compared. RESULTS: The analysis included 77 patients with lymphoma [median age, 71 (64-79)] years. The median period to PC1 from the initial diagnosis was 395 (180-1,086) days. ROC analysis revealed an optimal PC intervention timing of 140 days. OS was significantly longer in the early group than that in the delayed group. The most common counseling details for the PCT were symptom relief and palliative care transfer (36.8% and 35.2%, respectively). CONCLUSION: This real-world evaluation of PC intervention for inpatients with lymphoma revealed that PC intervention was provided at approximately 13 months following initial diagnosis. EPC intervention from diagnosis to 140 days may improve OS in patients with lymphoma; however further large-scale studies are required to verify this finding.