The emerging emetogenicity of trifluridine/tipiracil (TAS­102) from patient self-reporting: a multicenter, prospective, observational study.

BACKGROUND: Trifluridine/tipiracil (TAS-102) is an oral anticancer drug with adequate efficacy in unresectable colorectal cancer, but frequently also induces chemotherapy-induced nausea and vomiting (CINV). To investigate the occurrence of CINV and antiemetic therapy in patients with colorectal cancer treated with TAS-102 (JASCC-CINV 2001). METHODS: We conducted a multicenter, prospective, observational study in patients with colorectal cancer who received TAS-102 without dose reduction for the first time. Primary endpoint was the incidence of vomiting during the overall period. Secondary endpoints were the incidence of nausea, significant nausea, anorexia, other adverse events (constipation, diarrhea, insomnia, fatigue, dysgeusia) and patient satisfaction. Patient diaries were used for primary and secondary endpoints. All adverse events were subjectively assessed using PRO-CTCAE ver 1.0. and CTCAE ver 5.0. RESULTS: Data from 100 of the 119 enrolled patients were analyzed. The incidence of vomiting, nausea, and significant nausea was 13%, 67%, and 36%, respectively. The incidence of vomiting in patients with and without prophylactic antiemetic therapy were 20.8% and 10.5%, respectively. Prophylactic antiemetics were given to 24% of patients, of whom 70% received D2 antagonists. Multivariate Cox proportional hazards analysis showed that experience of CINV in previous treatment tended to be associated with vomiting (hazard ratio [HR]: 7.13, 95% confidence interval [CI]: 0.87-58.5, P = 0.07), whereas prophylactic antiemetic administration was not (HR: 1.61, 95 CI: 0.50-5.21, P = 0.43). With regard to patient satisfaction, the proportion of patients who were "very satisfied," "satisfied," "slightly satisfied" or "somewhat satisfied" was 81.8%. CONCLUSIONS: The low incidence of vomiting and high patient satisfaction suggest that TAS-102 does not require the use of uniform prophylactic antiemetic treatments. However, patients with the experience of CINV in previous treatment might require prophylactic antiemetic treatment.

Medication reconciliation by pharmacists for pre-admission patients improves patient safety.

BACKGROUND: Medication errors related to the pre-admission medication history obtained on admission are a major cause of medication error during hospitalization. Medication reconciliation (MR) improves patient safety through the detection of inadvertent medication discrepancies at transitions of care. The aim of this study was to evaluate the effect of MR by pharmacists for patients prior to hospital admission on the incidence of medication errors in the early post-admission period. PATIENTS AND METHODS: Patients admitted to the orthopedic ward for surgery between April 2012 and March 2020 were included. Pharmacist-led MR for pre-admission patients was started on April 1, 2017. The incidence of medication errors related to pre-admission medications that occurred during hospitalization were compared between the pre- and post-initiation of pharmacist-led MR (pre-initiation: April 1, 2012 to March 31, 2015, post-initiation: April 1, 2017 to March 31, 2020). RESULT: In the post-initiation group, 94.2% (1245/1321) of patients who were taking medications on admission had a pharmacist-led MR before admission. The proportion of patients whose physicians ordered the prescription of their pre-admission medications at the time before hospitalization to continue from admission was significantly higher in the post-initiation group than in the pre-initiation group (47.4% vs. 1.0%, p < 0.001). The incidence of medication errors related to pre-admission medications during hospitalization was significantly lower in the post-initiation group than in the pre-initiation group (1.83% vs. 0.85%, p = 0.025). Pharmacist-led MR prior to admission was a significant protective factor against incidents related to pre-admission medication (odds ratio (OR), 0.3810; 95% confidence interval (CI); 0.156-0.9320, p = 0.035). CONCLUSION: Pharmacist-led MR for patients prior to hospital admission led to a reduction in medication errors related to pre-admission medications during hospitalization. Patient safety during hospitalization can be improved by accurate medication histories provided early by pharmacists.

Dexamethasone-sparing strategies in anthracycline and cyclophosphamide-based chemotherapy with a focus on 5-HT3 receptor antagonists: a network meta-analysis.

Background: The effectiveness of a dexamethasone-sparing strategy in the treatment of breast cancer with anthracycline-cyclophosphamide therapy when combined with first-generation 5-HT3 receptor antagonists (RAs) and neurokinin-1 RAs is unclear. This is attributable to a lack of evidence from direct comparison of multiple doses of DEX to a single dose of DEX in combination with first-generation 5-HT3 RAs in anthracycline-cyclophosphamide therapy. Our goal was to clarify the impact of dexamethasone-sparing strategies that involve both first-generation 5-HT3 RAs and palonosetron when combined with neurokinin-1 RAs, using a network meta-analysis. Materials and methods: A literature search was conducted on PubMed/Medline for articles published up to July 4, 2023. We included randomized controlled trials which assessed the efficacy of antiemetic regimens which combined 5-HT3 RAs and dexamethasone, with or without neurokinin-1 RAs, for the initial dose in anthracycline-cyclophosphamide therapy for patients with breast cancer. The primary outcome was the proportion of patients achieving a complete response during the delayed phase (CR-DP). Results: The difference in the proportion of patients achieving CR-DP between multiple and single doses of dexamethasone was 0.1% (95%CI: -12.4 to 12.5) with palonosetron and neurokinin-1 RAs, compared to 5.3% (95%CI: -13.4 to 23.0) with a single dose of a first-generation 5-HT3 receptor antagonist. Additionally, the difference was 12.7% (95% CI: -2.8 to 28.2) when comparing palonosetron against first-generation 5-HT3 RAs in combination with a single dose of dexamethasone and neurokinin-1 RAs. Conclusion: Palonosetron is recommended rather than a single dose of first-generation 5-HT3 RAs in dexamethasone-sparing strategies for anthracycline-cyclophosphamide therapy.

CONUT score as a predictor for anamorelin efficacy in patients with cancer cachexia receiving chemotherapy.

BACKGROUND: Anamorelin is expected to improve cancer cachexia by increasing lean body mass (LBM) due to increased appetite and protein synthesis. However, the effect of anamorelin on cancer cachexia in real-world practice is unclear. The purpose of this study was to evaluate the efficacy and safety of anamorelin and to identify predictors of efficacy on treatment with anamorelin. METHODS: We retrospectively analyzed data from patients with cancer cachexia treated with chemotherapy between May 2021 and August 2022. Efficacy of anamorelin was evaluated using LBM, with "12-week sustained effective response" to anamorelin treatment defined as maintenance or an increase in LBM for 12 weeks. We examined factors associated with "12-week sustained effective response" to anamorelin treatment using a multivariable logistic model that included controlling nutritional status (CONUT) score, an objective assessment of nutritional disorders, and the modified Glasgow prognostic score (mGPS), which scores the cachexia status of cancer patients. To assess patient subjective quality of life (QOL) changes related to eating after starting anamorelin treatment, we used a questionnaire (QOL-ACD appetite-related items: Q8, 9, 11). Adverse events were evaluated in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. RESULTS: On analysis of data from 40 patients, 23 patients showed a 12-week sustained effective response to anamorelin (57.5%). At 12 weeks, LBM significantly increased by 1.63 ± 3.73 kg (mean ± SD). Multivariable logistic analysis revealed that a low CONUT score was significantly associated with "12-week sustained effective response" to anamorelin treatment (adjusted odds ratio: 13.5, 95% confidence intervals: 2.2-84.2, P = 0.004). QOL assessment showed a trend toward increased appetite and enjoyment of meals after anamorelin initiation. Five patients (12.5%) had an increase in HbA1c of more than 1.0% during the 12 weeks after the start of anamorelin. No patient had QT interval prolongation or grade 3 or higher hepatic transaminase elevation. CONCLUSION: Anamorelin may maintain or increase LBM with tolerable safety in patients with cancer cachexia undergoing chemotherapy. A low CONUT score, despite meeting criteria for cancer cachexia, is suggested as a predictor for the efficacy of anamorelin, indicating that patients with a low CONUT score may benefit from early introduction of anamorelin.

The role of pharmacists in multimodal cancer cachexia care.

Cancer cachexia is a complex syndrome, and multidisciplinary management has the potential to improve patient outcomes and efficiency of care. Multidisciplinary management consists primarily of exercise, nutrition, and pharmacotherapy. The pharmacist's role in cancer cachexia is to contribute to appropriate pharmacotherapy practices. For example, anamorelin is an oral drug with ghrelin-like effects that may improve the pathogenesis of cancer cachexia by stimulating appetite and increasing food intake and body weight. Many patients with cancer cachexia are under treatment with anticancer agents, and pharmacists need to determine whether symptoms such as anorexia and nausea are due to cancer cachexia or anticancer agents. Based on that determination, they are then expected to suggest supportive care to the physician. Provision of multidisciplinary care for cancer cachexia requires communication with not only physicians but also with nurses, dietitians, and other professionals so that nutritional therapy can be provided at the time cachexia is detected. However, the role of pharmacists in the management of cancer cachexia is not well established, and there is no evidence that pharmacist interventions are of benefit to patients. In this article, to contribute to the treatment of cancer cachexia by multidisciplinary care, we describe the role of pharmacists in cancer cachexia as currently practiced at our hospital. We also consider future challenges to this type of multidisciplinary care. Evidence concerning multidisciplinary treatment of cancer cachexia is scarce, including therapeutic agents, and there is a current lack of collaboration among medical professionals and education in cancer cachexia. Solving these problems will require efforts in the practice and evaluation of treatment for cancer cachexia.