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.