[Second-Generation Antihistamines for Preventing Hypersensitivity Reactions during Anticancer Therapy-A Retrospective Study].

Hypersensitivity reactions are an adverse effect of anticancer drug therapy. Prophylactic administration of antiallergic drugs and steroids is recommended when administering drugs associated with a high hypersensitivity reaction incidence. First-generation antihistamines are generally used in this setting. These medications, however, induce drowsiness and sedation due to their inhibitory effects on the central nervous system. They are contraindicated in patients with angle-closure glaucoma and prostatic hyperplasia. Second-generation antihistamines are used as alternative drugs for such cases in our hospital. This study investigated the use of second-generation antihistamines at our hospital and examined their efficacy and safety. A total of 7 second-generation antihistamines were used at our hospital. Approximately 90% of the target patients were shifted from first-generation antihistamines to bilastine or desloratadine. The most frequent reasons for changing to second- generation antihistamines were drowsiness(32.3%)and car driving(24.2%). No central inhibitory side effects were observed upon consumption of second-generation antihistamines. Only 2 patients(3.2%)developed hypersensitivity reactions after changing to second-generation antihistamines. Our findings suggest that second-generation antihistamines are effective in preventing hypersensitivity reactions. These medications may be used in patients who have concerns regarding the central inhibitory side effects of first-generation antihistamines or their potential to exacerbate comorbidities. Their use can help improve the safety of anticancer drug therapy.

Assessing the ability of the Cancer and Aging Research Group tool to predict chemotherapy toxicity in older Japanese patients: A prospective observational study.

INTRODUCTION: The Cancer and Aging Research Group (CARG) prediction tool was designed in the United States to predict grade ≥ 3 chemotherapy-related adverse events (CRAE) in older patients. However, its usefulness among Japanese people, who have different sensitivities to anticancer drugs and life expectancy, remains unknown. We aimed to prospectively evaluate the utility of the CARG tool for predicting severe CRAE in older Japanese patients with cancer. MATERIAL AND METHODS: Patients with solid tumors aged 65 years and older who commenced anticancer drug regimens from April 2018 to October 2020 were divided into three groups (low, medium, and high-risk) based on their CARG risk scores. Toxicity was prospectively observed by a pharmacist. The primary objective was to evaluate the correlation between the incidence of grade ≥ 3 CRAE and the CARG risk score. The secondary objective was to evaluate hematological and non-hematological toxicities. CRAE incidence was compared among the three groups using a closed testing procedure: (1) Cochran-Armitage test for trend and (2) chi-square test for paired comparison. RESULTS: The patients (N = 165) had a median age of 71 years (range: 65-89 years). CRAE in patients divided into low-, medium-, and high-risk groups, based on CARG risk scores, were 39%, 55%, and 82%, respectively (low vs high; p < 0.001, medium vs high; p < 0.01). The incidence of severe hematologic toxicity was 37%, 35%, and 50% in the low-, medium-, and high-risk groups, respectively; the incidence of severe non-hematologic toxicity was 15%, 36%, and 65%, respectively (low vs medium; p < 0.01, low vs high; p < 0.001, and medium vs high; p < 0.01). DISCUSSION: To our knowledge, this is the first prospective observational study to validate the CARG prediction tool in older Japanese patients with cancer. The CARG risk score may be effective in predicting the development of non-hematologic toxicities. These results should be considered when administering chemotherapy to older Japanese patients with advanced solid tumors.

Incidence and Timing of Immune-Related Adverse Events in Immune-Checkpoint Inhibitor-Treated Patients: A Retrospective Observational Study.

BACKGROUND: Immune-checkpoint inhibitors (ICIs) are effective against various cancers; however, immune-related adverse events (irAEs) have been reported and the timing and risk factors are unknown. Therefore, we examined the incidence and timing of irAE occurrence. METHODS: Patients who received ICIs at our hospital between 1 April 2016 and 31 March 2020 were enrolled. Patients were classified into an irAE group or non-irAE group. In addition, we examined the onset time and symptoms of irAEs for each ICI type. RESULTS: A total of 80 patients received ICIs, of which 27 (33.8%) developed irAEs. The incidence of irAEs was 35.3% for nivolumab, 35.5% for pembrolizumab, and 28.6% for atezolizumab. The incidence of pneumonitis was 12.5%, 8.8% for dermatologic adverse events, and 6.3% for thyroid dysfunction. The earliest case of onset was after the 1st course, and the latest cases occurred after the 66th course. By the sixth course, 69% of the irAEs occurred. The positive rates for anti-thyroid peroxidase and anti-thyroglobulin antibodies were higher in the irAE group compared to the non-irAE group. CONCLUSIONS: Our findings suggest a high probability of irAEs occurring early in ICI treatment, with a diverse range of symptoms. This underscores the need for vigilant monitoring and tailored patient management during the initial courses of ICI therapy.

Evaluation of Remdesivir for Mildly to Moderately Ill Patients with COVID-19: A Single-Arm, Single-Center, Retrospective Study.

Background and Objectives: Remdesivir (RDV) is the first antiviral agent approved in Japan for the treatment of coronavirus disease 2019 (COVID-19). The aim of our study was to assess the efficacy and safety of RDV treatment in mildly to moderately ill patients with COVID-19. Materials and Methods: A single-center, retrospective study was performed in Fukuoka University Chikushi Hospital. Patients admitted to our hospital from June to October 2021 for RDV treatment against COVID-19 were enrolled. The primary end point was clinical status on days 10 and 14, using a 6-point ordinal scale ranging from death (category 6) to discharge (category 1). Adverse events were assessed and graded using the Japanese version of Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: In total, 47 COVID-19 patients receiving RDV treatment were assessed during the study period. Thirty-four (72.3%) out of 47 patients required oxygen therapy. Out of these 34 patients, 30 (88.2%) showed a 2-point clinical improvement on day 14 after RDV was initiated. Serum alanine aminotransferase levels were elevated in three patients (6.4%) (CTCAE Grade 3) and neutropenia was detected in one patient (2.1%) out of the 47 patients. Conclusions: RDV may be highly effective, with good safety profiles, in patients with COVID-19 requiring oxygen therapy.

Estimating the effect of optimizing anticancer drug vials on medical costs in Japan based on the data from a cancer hospital.

BACKGROUND: The substantial increase in the use of expensive anticancer drugs has been accompanied by an increase in the amount of disposing residual liquid from drug preparations. Many Western countries, including the United States, have implemented drug vial optimization (DVO) to prevent the waste of anticancer drugs and have reported the reductions in the total drug costs. This study was designed to estimate the expected reduction in spending on anticancer drugs by Japanese cancer hospitals when DVO was implemented instead of individual preparations and to test the effectiveness of this approach. METHODS: We investigated the doses of drugs used and quantity specifications for individually prepared vials for patients who received anticancer drug treatment in December 2017 at the Outpatient Treatment Center of the National Cancer Center Hospital East. Based on these findings, we calculated the total quantity of each drug used on a given day, and the minimum cost for preparation of the number of specified combinations corresponding to the total cost (DVO preparation). Based on the differences in these two costs, we estimated the economic impact of implementing DVO. RESULTS: While the cost for anticancer drugs for the 1-month study period was US$3,305,595 (US$1 = \110) for individual preparations, the estimated cost for DVO preparations was US$3,092,955, equivalent to a reduction of US$212,640. CONCLUSIONS: Based on these study results, implementation of DVO-based preparation of injectable anticancer drugs in Japan in 2017 would have resulted in saving approximately US$460 million. This calculation revealed the need for the Japanese government to modify the methods employed to calculate drug costs in the insurance system and develop policies for the proper and optimal use of medical resources.

Association of Self-Reported Medication Adherence with Potentially Inappropriate Medications in Elderly Patients: A Cross-Sectional Pilot Study.

BACKGROUND: Polypharmacy (PP) and potentially inappropriate medications (PIMs) cause problematic drug-related issues in elderly patients; however, little is known about the association between medication adherence and PP and PIMs. This study evaluated the association of self-reported medication adherence with PP and PIMs in elderly patients. METHODS: A cross-sectional pilot study was conducted using data collected from electronic medical records of 142 self-administering patients aged ≥65 years, excluding emergency hospitalization cases. Self-reported medication adherence was assessed using the visual analogue scale (VAS). RESULTS: Of the 142 patients, 91 (64.1%) had PP and 80 (56.3%) used at least one PIM. In univariate analysis, patients with a VAS score of 100% had a significantly higher number of female patients and ≥1 PIM use compared to other patients. We found no association between the VAS score and PP. In multivariable analysis, the use of PIMs was significantly associated with a VAS score of 100% (odds ratio = 2.32; 95% confidence interval = 1.16-4.72; p = 0.017). CONCLUSIONS: Use of PIMs by elderly patients is significantly associated with self-reported medication adherence. Pharmacists should pay more attention to prescribed medications of self-administering elderly patients in order to improve their prescribing quality.

[A Survey of the Adverse Effects and Influence of Concomitant Drugs for Methotrexate Intrathecal Administration].

In general, the intraventricular administration of cytotoxic antitumor drugs provides a high drug concentration in the cerebrospinal fluid with a reduced risk of systemic adverse reactions. Methotrexate (MTX) high-dose therapy requires close monitoring when performed in combination with trimethoprim-sulfamethoxazole (ST) therapy and proton pump inhibitor (PPI) and nonsteroidal anti-inflammatory drug administration for excretion delay and toxicity enhancement. While the frequency of systemic side effects is thought to be low with intrathecal administration, such effects do rarely but occasionally occur. We must consider drug interactions with combination therapy as a potential factor inducing such effects. We examined the patients who received MTX intrathecal administration at Fukuoka University Hospital from January 2013 to December 2014 with respect to the onset of side effects and combination therapy. MTX intrathecal administration was performed a total of 79 times in 27 patients. In five of these 27 patients, MTX intrathecal administration was performed twice a week, and hematotoxicity and non-hematotoxicity developed in two patients in whom ST was also administered. On the other hand, even if ST and/or PPI was administered, no side effects were observed in the patients administered levofolinate.

Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells.

Adult T-cell leukemia/lymphoma (ATL), an aggressive T-cell malignancy that develops after long-term infection with human T-cell leukemia virus (HTLV-1), requires new treatments. Drug repositioning, reuse of a drug previously approved for the treatment of another condition to treat ATL, offers the possibility of reduced time and risk. Among clinically available angiotensin II receptor blockers, telmisartan is well known for its unique ability to activate peroxisome proliferator-activated receptor-γ, which plays various roles in lipid metabolism, cellular differentiation, and apoptosis. Here, telmisartan reduced cell viability and enhanced apoptotic cells via caspase activation in ex vivo peripheral blood monocytes from asymptomatic HTLV-1 carriers (ACs) or via caspase-independent cell death in acute-type ATL, which has a poor prognosis. Telmisartan also induced significant growth inhibition and apoptosis in leukemia cell lines via caspase activation, whereas other angiotensin II receptor blockers did not induce cell death. Interestingly, telmisartan increased the LC3-II-enriched protein fraction, indicating autophagosome accumulation and autophagy. Thus, telmisartan simultaneously caused caspase activation and autophagy. A hypertension medication with antiproliferation effects on primary and leukemia cells is intriguing. Patients with an early diagnosis of ATL are generally monitored until the disease progresses; thus, suppression of progression from AC and indolent ATL to acute ATL is important. Our results suggest that telmisartan is highly effective against primary cells and leukemia cell lines in caspase-dependent and -independent manners, and its clinical use may suppress acute transformation and improve prognosis of patients with this mortal disease. This is the first report demonstrating a cell growth-inhibitory effect of telmisartan in fresh peripheral blood mononuclear cells from leukemia patients.

Fluorous-assisted metal chelate affinity extraction technique for analysis of protein kinase activity.

We have developed a fluorous affinity-based extraction method for measurement of protein kinase activity. In this method, a fluorescent peptide substrate was phosphorylated by a protein kinase, and the obtained phosphopeptide was selectively captured with Fe(III)-immobilized perfluoroalkyliminodiacetic acid reagent via a metal chelate affinity technique. Next, the captured phosphopeptide was selectively extracted into a fluorous solvent mixture, tetradecafluorohexane and 1H,1H,2H,2H-tridecafluoro-1-n-octanol (3:1, v/v), using the specificity of fluorous affinity (fluorophilicity). In contrast, the remained substrate peptide in the aqueous (non-fluorous) phase was easily measured fluorimetrically. Finally, the enzyme activity could be assayed by measuring the decrease in fluorescence. The feasibility of this method was demonstrated by applying the method for measurement of the activity of cAMP-dependent protein kinase (PKA) using its substrate peptide (kemptide) pre-labeled with carboxytetramethylrhodamine (TAMRA).