Published papers

Background: Proton pump inhibitors (PPIs) reduce the bioavailability of several anticancer drugs. The impact of PPIs co-administered with cyclin-dependent kinase 4 and 6 inhibitors is controversial. We aimed to clarify whether the concomitant use of PPIs impacts palbociclib and abemaciclib effectiveness in breast cancer treatment. Patients and Methods: This multicenter, retrospective, observational study, conducted across four medical institutions in Japan, consecutively included patients with endocrine-resistant metastatic breast cancer, receiving palbociclib or abemaciclib between December 2017 and August 2022. Propensity score-matched analyses were performed. Treatment efficacy and safety with and without PPIs were compared. Progression-free survival and overall survival were estimated using the Kaplan–Meier method and compared using a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio. Results: The study included 240 patients. After 1:1 matching, 112 patients were treated with and without PPIs. The median progression-free survival periods were 1.2 years in the PPI group and 1.3 years in the non-PPI group (hazard ratio, 1.19; 95% confidence interval [CI], 0.70–2.02). The median overall survival period was 3.6 years in the PPI group, whereas it was not reached in the non-PPI group (hazard ratio, 1.23; 95% CI, 0.61–2.47). Consistent results were obtained for subgroups receiving palbociclib (n = 177) and abemaciclib (n = 63) without propensity score matching. Moreover, adverse event incidence and severity were similar in both groups. Conclusion: The effectiveness of cyclin-dependent kinase 4/6 inhibitors is unlikely to be affected by concomitant PPI use. Future prospective pharmacokinetic studies are warranted.

我々は,ヒノキ科花粉の飛散が多かった2019年の,メール配信の「登録群」と「非登録群」における初期療法の実施状況と花粉症症状の評価,および登録前後のセルフメディケーションを含めた花粉症治療の患者満足度を比較検討した.花粉症症状の評価が最も高かったのは,「登録+初期療法」群であり,「登録+非初期療法」群,「非登録+初期療法」群,「非登録+非初期療法」群の順であった.さらに,セルフメディケーションを含めた花粉症治療の患者満足度も,「登録後」が「登録前」より高かった.以上より,ヒノキ科花粉飛散情報メール配信は,ヒノキ科花粉大量飛散年においても,患者の花粉回避に対する意識を高め,患者満足度の向上に寄与すると考えられる.(著者抄録)

目的:紙巻タバコや新型タバコ(加熱式タバコ、電子タバコ)に対する大学生の主観的有害性認識度(以下、認識度)が、喫煙防止・禁煙教育を行うことでどの様に変化するか講義前後で評価した。方法:共通教育科目において、癌疾患、慢性閉塞性肺疾患等の喫煙が関係する病態や禁煙補助剤の説明、さらに紙巻きタバコや新型タバコの有害性に関する90分の講義を3回行った。講義終了後、学生にアンケートを配布し、年齢、性別、3種類のタバコに関する認識度の変化(1:少ない〜5:多いの5段階)の記載を求めた。結果と考察:大学生への喫煙防止・禁煙教育において、講義後に喫煙に対する認識度は上昇しており有意差が認められた。3種類のタバコの中で認識度が最も高いのは、紙巻タバコであり、加熱式タバコ、電子タバコの順であった。紙巻タバコの有害性に関しては、小学校より継続的に教育されているが、新型タバコは近年販売されたばかりであり、毒性が低い等の宣伝が原因と考えられる。また、全ての種類のタバコの有害性に関して、女性の方が男性よりも認識度が高い傾向にあった。この理由として、女性は妊娠・出産等の健康面を考慮しているためと考えられる。一方、講義前の加熱式タバコや電子タバコの認識度が紙巻タバコよりも低い結果であった。特にニコチンやタールが入っていない電子タバコに関しては、講義前の認識度が最も低いため、電子タバコなら喫煙しても良いと考える多くの学生がいると懸念される。結論:大学生に対する紙巻きタバコや新型タバコに関する有害性認識度の調査から、大学生への新型タバコの有害性に関して教育する必要がある。(著者抄録)

2021年度の当大学薬学部の5年次生146名を対象に、実務実習事前学習の学業成績を調査し、実務実習における到達度評価の向上に関わる因子を評価した。146名の実務実習事前学習の学業成績は81.2±2.0点、最大値は86.0点、最小値は74.0点であった。平均値で本学が目標とするスコア3に到達していた項目は薬局実習では10項目中6項目、病院実習では11項目中4項目であり、薬局実習よりも病院実習で目標到達率が低かった。なかでも、「処方箋に基づく調剤」のうち「患者情報の把握」はスコア3以上に到達していた実習生が146人中85人(38.2%)と目標到達率の低い項目であった。今回の検討から、代表的8疾患への関わりを増やすことで到達度評価を向上させる可能性が示唆された。すなわち、少数の患者であっても代表的8疾患に幅広く関わりを経験させる目標を優先させた方が実習生の到達度評価が向上することが示された。

Purpose: As the major toxicity induced by pemetrexed plus carboplatin is severe hematologic toxicities, the aim of this study was to determine the risk factors for severe hematologic toxicities in lung cancer patients. Methods: We retrospectively investigated data from lung cancer patients who had received pemetrexed plus carboplatin, with or without bevacizumab. This observational study was carried out at Ehime University Hospital using electronic medical records dating from July 2009 to March 2015. Severe hematologic toxicities were defined as grade 3 or 4, according to the Common Terminology Criteria for Adverse Events, version 4.0. Results: Forty-two patients were included in the study. The incidence of grade 3 or 4 hematologic toxicities during the first cycle of chemotherapy and during all cycles was 19.0% and 16.1%, respectively. Multivariate time-depend generalized estimating equations logistic regression analysis revealed that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) was significantly associated with an increased risk of severe hematologic toxicities during all cycles (adjusted odds ratio (OR): 8.32, 95% confidence interval (CI): 1.27–54.38; p = 0.03), whereas creatinine clearance of <45 mL/min was not significantly associated with an increased risk of severe hematologic toxicities during all cycles (adjusted OR: 0.91, 95% CI: 0.25–3.34; p = 0.88). Conclusions: The results suggest that severe hematologic toxicities in patients receiving carboplatin-based pemetrexed may be significantly induced by the inhibition of renal tubular pemetrexed secretion through drug–drug interactions between NSAIDs and pemetrexed rather than through glomerular filtration of pemetrexed, even with moderate to sufficient renal function.

Purpose: The aim of this study was to clarify the risk factors for discontinuing tegafur/gimeracil/oteracil potassium (S-1) adjuvant chemotherapy following gastrectomy in patients with gastric cancer. Methods: We retrospectively investigated patients with curatively-resected gastric cancer who received S-1 adjuvant chemotherapy. S-1 was administered orally at 80-120 mg/day, depending on body surface area, on days 1-28 every 6 weeks for 1 year. The dose and treatment schedule were modified at the clinicians' discretion, according to toxicity. Results: Seventy-one patients were included in the study, 26 of whom discontinued S-1 therapy. The relapse-free survival rates in the S-1-completed and S-1-discontinuation groups at 5 years post-surgery were 88.1% and 55.8%, respectively. The overall survival rates in the S-1-completed and S-1-discontinuation groups at 5 years post-surgery were 89.4% and 59.8%, respectively. The hazard ratios for relapse and death were significantly lower in the S-1-completed group compared with those in the S-1-discontinuation group (0.18; p<0.001 and 0.19; p=0.002, respectively). Multivariate logistic regression analysis revealed that S-1 discontinuation was significantly associated with an initial overdose of S-1, having stage I cancer, creatinine clearance <66 mL/min, and a side effect of nausea. Conclusions: These results suggest that assessing renal function to avoid initial overdose of S-1, together with the early management of side effects, may support the continuation of S-1 adjuvant chemotherapy in patients with gastric cancer.

To prepare for a new practical training scheme starting in 2019 based on a revised-model core curriculum for pharmaceutical education that incorporates outcome-based education, rubric-based assessment of student performance was implemented in practical training between May and July of 2018. The goals were to evaluate the rubric-based assessment to identify ways to improve it for appraising pharmaceutical students. All fifth-year students of the Keio University Faculty of Pharmacy in 2018 (n = 160) self-assessed their performance during practical training using evaluation sheets in a rubric form comprising three general instructional objectives with 10 task descriptions developed by the Japanese Pharmaceutical Association or Japanese Society of Hospital Pharmacists. Compared to the commencement of the training, the median evaluations in all tasks significantly increased at the completion of the practical training in the community pharmacy and the hospital settings. Survey questionnaires were administered to the students after the practical training. Customer satisfaction analysis identified two main areas for improvement of the rubric-based assessment for student growth: (1) students' lack of understanding of the rubric-based assessment in hospitals and (2) mentors' lack of understanding of it in both settings. The results suggest that rubric-based assessment is a feasible method for assessing pharmaceutical student performance during practical training. Additionally, the Faculty of Pharmacy should provide and disseminate information to students and mentors about rubric-based assessment and support mentors' efforts for student progress during practical training.

Objective: Platinum- and anthracycline-based chemotherapy regimens cause nausea and vomiting in clinical practice, resulting in the deterioration of patients’ QoL, discontinuation of chemotherapy, and reduced therapeutic outcomes. Using pica behavior as an indicator, we aimed to clarify whether anamorelin, an orally active ghrelin receptor agonist, exerts antiemetic effects against cisplatin-induced nausea and vomiting in rats. Materials and methods: Sprague–Dawley rats were treated with cisplatin (5 mg/kg, i.p.), three-drug or four-drug antiemetics (granisetron [0.3 mg/kg, p.o.], dexamethasone [1.5 mg/kg, p.o.], fosaprepitant [12.5 mg/kg, i.p.], with or without anamorelin [30 mg/kg, p.o.]). Data on kaolin intake, normal food intake, and spontaneous motor activity (SMA) were recorded 1 d before and 5 d after cisplatin administration. Body weight (BW) was measured daily, and the percentage change in BW from baseline was calculated. Results: At the primary endpoint, kaolin intake was significantly higher in the cisplatin-only group than in the pretreatment and vehicle groups (p < 0.05). Additionally, kaolin food intake was not significantly low in cisplatin-treated mice treated with three-drug antiemetics with or without anamorelin. At the secondary endpoints, normal food intake, SMA, and percentage change in BW were significantly lower in the cisplatin-only group than in the vehicle group. Conclusion: Our findings suggest that the prophylactic administration of standard three-drug antiemetics, besides anamorelin, may not improve cisplatin-induced nausea and vomiting. Further studies using methods suitable for evaluating anamorelin levels are required.

This study aimed to clarify diverse values toward career visions for hospital pharmacists. A self-administered online questionnaire survey was delivered to live and on-demand release attendees at a symposium about sustainable career paths for pharmacists at the 32nd annual meeting of the Japanese Society of Pharmaceutical Health Care and Sciences between September 23rd and November 14th, 2022. Correspondence analyses of text mining were conducted to assess the association between the participants’ perspectives on career visions and their backgrounds consisting of sex and generation. The recovery rate was 81.9% (136/166). The majority of respondents were women (61.4%), aged ≥40 years (66.1%). Correspondence analysis of career vision for pharmacists showed that respondents who were ≥20–30 years were associated with the research topic, whereas those who were ≥40 years were associated with the director of a pharmacy and worked until retirement age. In contrast, there was no difference in career visions for pharmacists based on sex. The median satisfaction score of the symposium was 6 [interquartile range (IQR): 5–6] in the entire population, as conveyed using a seven-point Likert scale. Interestingly, the median satisfaction scores of the symposium were significantly higher for men in management positions than women in non-management and management positions (p=0.0106 and p=0.0031, respectively). In conclusion, we believe that career support tailored to everyone’s values could enable hospital pharmacists to realize their career visions.

Background: Female sex and younger age are reported risk factors for chemotherapy-induced nausea and vomiting (CINV) in highly emetogenic chemotherapy, but the underlying mechanism has not been elucidated. The purpose of this study was to clarify the impact of menopause on CINV. Methods: This retrospective observational study analyzed data from consecutive patients who received their first cycle of perioperative anthracycline-based chemotherapy for breast cancer between January 2018 and June 2020. The endpoints were association between CINV (vomiting, ≥Grade 2 nausea, complete response [CR] failure) and menopause as well as the association between CINV and follicle-stimulating hormone [FSH]/estradiol [E2]. Results: Data for 639 patients were analyzed. Among these patients, 109 (17.1%) received olanzapine (four antiemetic combinations) and 530 (82.9%) did not (three antiemetic combinations). Premenopausal state (amenorrhea lasting ≥12 months) was significantly associated with ≥Grade 2 nausea and CR failure in univariate analysis but not in multivariate analysis. The premenopausal FSH/E2 group (defined by serum levels; FSH <40 mIU/mL and E2 ≥20 pg/mL) had a significantly higher rate of ≥Grade 2 nausea than the postmenopausal FSH/E2 group (FSH ≥40 mIU/mL and E2 <20 pg/mL) (48.8% vs. 18.8%, p = 0.023). Conclusions: Our results suggest that changes in FSH and E2 due to menopause may affect the severity of nausea and that FSH and E2 (especially FSH) levels might be useful indicators for CINV risk assessment.

Screening for total pain and sharing of patient information including adverse events for patients receiving chemotherapy by medical staff is needed in clinical practice. We introduced a sharing system for patient-oriented outcome sheets via a touch panel at an outpatient chemotherapy clinic. This study aimed to assess whether the system contributes to the improved management of treatment-related adverse events. We retrospectively analyzed data from a total of 215 patients at Ehime University Hospital using their electronic medical records from April to August 2015. Forty of these patients had received interventions relating to treatment-related adverse events. The proportion of a total number of interventions before and after the sharing system was 42/282(14.9%)and 45/215(20.9%), respectively. The proportion of a total number of interventions at the first course of outpatient chemotherapy also increased from 9/40(22.5%)to 14/40(35%)compared with before the sharing system. The purpose of interventions were for insomnia, anorexia, and cancer-related pain, etc., listed in order of degree of frequency. These results suggest that a sharing system of patient-reported interview sheets contributes to tracking treatment -related adverse events and aids in ensuring interventions can be efficiently performed by multidisciplinary team members.

Purpose: The therapeutic benefit of a three-drug combination of antiemetics has not been established in moderately emetogenic chemotherapy (MEC). The aim of this study was to compare the antiemetic effectiveness and cost-saving of palonosetron plus dexamethasone (control group) with aprepitant, granisetron, and dexamethasone (study group) in cancer patients who received MEC. Methods: We switched the standard antiemetic treatment from the control group to the study group in gastrointestinal cancer patients who received MEC after October 2015. The antiemetics in both groups were modified using salvage antiemetic therapy at the clinicians' discretion, according to the severity of chemotherapy-induced nausea and vomiting. We retrospectively reviewed the electronic medical records from patients, before and after switching groups, from between April 2014 and March 2016. Results: We evaluated 443 treatment courses in 83 patients. The proportion of courses that included salvage antiemetic therapy in the control group and the study group was 34.8 % (116/333) and 8.2 % (9/110), respectively, and was statistically significant (p < 0.001). The mean integrated costs of antiemetics per course in the control group and the study group were 193 ± 55 USD and 143 ± 38 USD, respectively. Multivariate logistic regression analysis revealed that the study group was significantly associated with a reduced risk of requiring salvage antiemetic therapy (p = 0.038). Conclusions: These results suggest that the antiemetic effectiveness and cost-saving of a three-drug combination of aprepitant, generic granisetron, and dexamethasone was superior to a two-drug combination of palonosetron plus dexamethasone in gastrointestinal cancer patients who received MEC.

Community pharmacies play a significant role in home healthcare. However, patient information from hospitals is not shared with community pharmacies. We attempted the bidirectional sharing of patient information regarding chemotherapy between hospitals and community pharmacies. We developed a “medicine message board,” which was a modified prescription format. Hospital pharmacists recorded information regarding patients taking tegafur/gimeracil/oteracil (S-1) on the message board. In turn, community pharmacists monitored side effects in the S-1 patients and returned the information by fax to our hospital also using the message board. A medical clerk entered the side effects into the electronic medical record, providing feedback to doctors. We distributed questionnaires to community pharmacies around our hospital between December 2013 and January 2014 and assessed their understanding using a five-point Likert scale (where 1 = insufficiency and 5 = sufficiency). The results showed that the mean scores on understanding about the presence or absence of cancer notification before and after the initiation of the message board were 2.10 ± 1.02 and 4.20 ± 1.06, respectively. The mean understanding about the name of a cancer patient's disease before and after the message board was 2.25 ± 0.91 and 4.45 ± 0.83, respectively. All these differences were significant. Understanding about the purpose of treatment, dose adjustments of S-1 due to body surface area and renal function, administration schedule, presence or absence of combination chemotherapy, pharmaceutical instructions, treatment adherence, and side effects monitoring were also significantly improved in community pharmacies after the initiation of the message board. These results suggest that there is scope to improve the support provided to oral chemotherapy patients by hospitals and community pharmacists.