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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., Competing Interests: DW reports honoraria from Chugai. HI reports receiving consulting fees from Eisai and Taiho; honoraria from Astellas, AstraZeneca, Chugai, Daiichi Sankyo, Eli Lilly, Nippon Kayaku, Ono, Sawai, Taiho, and Yakult. RK reports honoraria from Janssen. HF reports honoraria from Chugai, Daiichi Sankyo, Kyowa Kirin, Ono, Sanofi and Taiho. KK reports grants from Kyowa Kirin; honoraria from Tsumura Pharmaceuticals. MF reports honoraria from Daiichi Sankyo, Taiho, Chugai, Eisai, Lilly, and Nihon-Kayaku. AS reports institutional grants from Nippon Kayaku, Asahi Kasei Pharma, Chugai Pharm, Taiho Pharm, Daiichi Sankyo, Japan Blood Products Organization, Mochida Pharm, Sun Pharma; honoraria from Toa Eiyo, Asahi Kasei Pharma, Daiichi Sankyo, Pfizer, Eisai, Nippon Shinyaku, Kyowa Kirin, Tsumura, Towa Pharmaceutical, Nippon Kayaku, Mochida Pharmaceutical, EA Pharma, Yakult Honsha, Chugai Pharmaceutical. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Watanabe, Iihara, Kobayashi, Fujii, Mori, Kumada, Shimizu, Futamura and Suzuki.)

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., (© 2024. The Author(s).)

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 4 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 period was 1.2 years in the PPI group and 1.3 years in the non-PPI group (hazard ratio, 1.19; 95% 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. 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., (© The Author(s) 2024. Published by Oxford University Press.)

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., (© 2024. The Author(s).)

Background: This study evaluated the non-inferiority of dexamethasone (DEX) on day 1, with sparing on days 2-4 in cisplatin-based chemotherapy., Methods: Patients with malignant solid tumors who were treated with cisplatin (≥50 mg/m²) were randomly assigned (1:1) to receive either DEX on days 1-4 (Arm D4) or DEX on day 1 (Arm D1) plus palonosetron, NK-1 RA, and olanzapine (5 mg). The primary endpoint was complete response (CR) during the delayed (24-120 h) phase. The non-inferiority margin was set at -15%., Results: A total of 281 patients were enrolled, 278 of whom were randomly assigned to Arm D4 (n = 139) or Arm D1 (n = 139). In 274 patients were included in the efficacy analysis, the rates of delayed CR in Arms D4 and D1 were 79.7% and 75.0%, respectively (risk difference -4.1%; 95% CI -14.1%-6.0%, P = 0.023). However, patients in Arm D1 had significantly lower total control rates during the delayed and overall phases, and more frequent nausea and appetite loss. There were no significant between-arm differences in the quality of life., Conclusion: DEX-sparing is an alternative option for patients receiving cisplatin; however, this revised administration schedule should be applied on an individual basis after a comprehensive evaluation., Clinical Trials Registry Number: UMIN000032269., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Olaparib and niraparib (poly adenosine diphosphate [ADP]-ribose polymerase [PARP] inhibitors) have significant antitumor action in patients with ovarian cancer. However, the incidence of nausea and vomiting among patients on these drugs in clinical trials is rather high. There are no guidelines on antiemetic treatment for nausea caused by oral anticancer agents. This study aimed to investigate the incidence of nausea and vomiting caused by PARP inhibitors and the actual situation of antiemetic therapy in patients with gynecologic cancer. Methods: Patients with gynecologic cancer who were scheduled to receive PARP inhibitors were enrolled. Data on PARP inhibitor-induced nausea and vomiting were collected from patient diaries for 21 days. The primary endpoint was the incidence of vomiting during the 21 days after starting olaparib and niraparib. Results: Overall, between January 2020 and March 2023, 134 patients were enrolled. Of the 129 patients who were evaluated, 28 (21.7%) received prophylactic antiemetics for 21 days, and 101 (78.3%) did not. The overall incidence of PARP inhibitor-induced vomiting was 16.3%. The incidence of vomiting in the group that did not receive antiemetic prophylaxis was 13.9%. On dividing the group that did not receive antiemetic prophylaxis into the olaparib and niraparib subgroups, the incidence of vomiting was found to be 18.6% for the olaparib group and 10.3% for the niraparib group. Conclusion: The incidence of emesis without antiemetic prophylaxis among patients on olaparib and niraparib ranged from 10% to 30%. Therefore, olaparib and niraparib can be classified in the low emetogenic risk and prophylactic antiemetic therapy at the time of treatment initiation may be unnecessary., Competing Interests: Competing Interests: Ms. Yamamoto received personal fees from Chugai outside of the submitted work. Dr. Tsuchiya received personal fees from Chugai, Taiho, Ono, Sun Pharma, Kyowa-Kirin, Pfizer, Eizai, and Daiichi Sankyo outside the submitted work. Dr. Iihara received personal fees from Taiho, Chugai, Yakult, Astellas, Eli Lilly, Daiichi Sankyo, AstraZeneca, Nippon Kayaku, Ono, and Nippon Boehringer Ingelheim and consulting fees for their institution from Taiho and Eisai outside the submitted work. Dr. Suzuki received personal fees from Takeda and AstraZeneca outside of the submitted work. Mr. Watanabe received personal fees from Chugai outside of the submitted work. Dr. Suzuki A received personal fees from Toa Eiyo, Asahi Kasei, Daiichi Sankyo, Pfizer, Eisai, Nippon Shinyaku, Celltrion Healthcare Japan, Otsuka, Sandoz, Tsumura, Nipro, Taiho, Kyowa-Kirin, Nippon Chemiphar, Japan Blood Products Organization, Takeda, and Nippon Boehringer Ingelheim and grants for their institution from Nippon Kayaku, Asahi Kasei, Chugai, Taiho, Daiichi Sankyo, Japan Blood Products Organization, Mochida, and Sun Pharma outside the submitted work. Dr. Abe received personal fees from Taiho, Chugai, AstraZeneca, and Takeda outside the submitted work., (© The author(s).)

Background: Several studies have reported an association between severe neutropenia and long-term survival in patients treated with trifluridine-tipiracil (TAS-102). Because some of these studies failed to address immortality time bias, however, their findings should be interpreted with caution. Additionally, the association between severe neutropenia and survival in patients receiving TAS-102 in combination with bevacizumab (Bmab) remains unclear., Patients and Methods: We conducted a single-center retrospective cohort study in patients with colorectal cancer who received Bmab + TAS-102. We compared overall survival (OS) between patients who developed grade ≥ 3 neutropenia during the treatment period and those who did not. To account for immortal time bias, we used two approaches, time-varying Cox regression and landmark analysis., Results: Median OS was 15.3 months [95% CI: 14.1-NA] in patients with grade ≥ 3 neutropenia and 10.0 months [95% CI: 8.1-NA] in those without. In time-varying Cox regression, onset grade ≥ 3 neutropenia was significantly related to longer survival after adjustment for age and modified Glasgow Prognostic Score. Additionally, 30-, 60-, 90-, and 120-day landmark analysis showed that grade ≥ 3 neutropenia was associated with longer survival after adjustment for age and modified Glasgow Prognostic Score, with respective HRs of 0.30 [0.10-0.90], 0.65 [0.30-1.42], 0.39 [0.17-0.90], and 0.41 [0.18-0.95]., Conclusion: We identified an association between long-term survival and the development of severe neutropenia during the early cycle of Bmab + TAS-102 using an approach that addressed immortality time bias., (© 2023. The Author(s).)

Aims/introduction: Polypharmacy in diabetes patients is related to worse clinical outcomes. The aim of this study was to evaluate the usefulness of our countermeasure for polypharmacy, which combines a pharmacist check followed by a multidisciplinary team review in diabetic patients with polypharmacy., Methods: A single-center, retrospective observational study was conducted at Gifu University Hospital. Study participants included diabetic patients taking six or more drugs on admission to the diabetes ward between July 2021 and June 2022. Drugs which were discontinued by the present countermeasure were examined, and the number of drugs being taken by each patient was compared between admission and discharge., Results: 102 of 308 patients were taking six or more drugs on admission. The drugs being taken by these patients were evaluated by pharmacists using a checklist for polypharmacy. Eighty-four drugs which were evaluated as inappropriate or potentially inappropriate medications by pharmacists were discontinued following the multidisciplinary team review. The median and mean number of drugs taken by the 102 patients significantly decreased from 9.0 (IQR: 8-12) and 9.26 ± 2.64 on admission to 9.0 (IQR: 6-10) and 8.42 ± 2.95 on discharge (P = 0.0002). We followed up with these patients after discontinuation of the drugs and confirmed that their clinical status had not deteriorated., Conclusion: The present countermeasure for polypharmacy, which combines a pharmacist check based on a checklist for evaluating polypharmacy followed by a multidisciplinary team review, was useful for reducing the number of inappropriate or potentially inappropriate medications taken by diabetes patients with polypharmacy., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Trastuzumab deruxtecan is classified as an anticancer agent that poses a moderate emetic risk in the international guidelines for antiemetic therapy. The guidelines recommend emesis prophylaxis using a two-drug combination therapy comprising a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone (DEX). However, the high incidence of nausea and vomiting associated with trastuzumab deruxtecan is problematic. The National Comprehensive Cancer Network guideline version 1.2023 classified trastuzumab deruxtecan as having a high risk of emesis and changed its recommendation to a triplet regimen including a neurokinin-1 receptor antagonist (NK1RA). However, the emetogenic potential of trastuzumab-deruxtecan and the optimal antiemetic prophylaxis are controversial. Hence, this exploratory phase 2 study aimed to assess the efficacy and safety of treatment comprising 5-HT3RA and DEX with or without a NK1RA in preventing trastuzumab deruxtecan-induced nausea and vomiting. Methods: We conducted an open-label and randomized exploratory phase 2 study at 14 centers in Japan. Patients with breast cancer who were scheduled to receive trastuzumab deruxtecan were enrolled in this study. The patients were randomly assigned to receive granisetron and DEX (arm GD) or granisetron, DEX, and aprepitant (fosaprepitant; arm GDA). The primary endpoint was complete response (CR; no emesis or no rescue therapy) during the overall phase (120 h after the start of trastuzumab deruxtecan). Results: Between September 2020 and March 2023, 40 patients were randomly assigned to the GD (n = 19) or GDA (n = 21) arm. In the GDA arm, one patient who did not complete the use of the rescue medication listed in the diary was excluded from the efficacy analysis, which included the use of rescue medication. The CR rates during the overall phase were 36.8% and 70.0% in the GD and GDA arms, respectively (odds ratio 0.1334; 95% confidence interval [CI]: 0.0232-0.7672; P = 0.0190), with a difference of 33.2%. No grade 3 or 4 toxicity related to antiemetic therapy was observed. Conclusions: Patients receiving trastuzumab deruxtecan require triple therapy, including mandatory NK1RA administration., Competing Interests: Competing Interests: Dr. Iihara received personal fees from Taiho, Chugai, Yakult, Astellas, Eli Lilly, Daiichi Sankyo, AstraZeneca, Nippon Kayaku, Ono, and Nippon Boehringer Ingelheim as well as consulting fees for their institution from Taiho and Eisai outside the submitted work. Dr. Bando received personal fees from Daiichi Sankyo outside the submitted work. Dr. Mizuno received personal fees from Daiichi Sankyo, Chugai, Eisai, and AstraZeneca outside the submitted work. Dr. Kawaguchi received personal fees from Daiichi Sankyo, Chugai, and AstraZeneca outside the submitted work. Dr. Kawai received personal fees from AstraZeneca, Eisai, Kyowa-Kirin, Novartis, Chugai, Eli Lilly, MSD, and Pfizer outside the submitted work. Dr. Ishihara received personal fees from Nippon Kayaku, Kyowa-Kirin, Daiichi Sankyo, Eisai, and Chugai outside the submitted work. Dr. Nakada received personal fees from Daiichi Sankyo, Novartis Pharma, Pfizer, Chugai, and Eli Lilly outside the submitted work. Dr. Kojima received personal fees from Chugai, Novartis, Daiichi Sankyo, Eli Lilly, Kyowa-Kirin Eisai, Taiho, Pfizer, AstraZeneca, and MSD outside the submitted work. Dr. Higuchi and Ms. Furuta received personal fees from Daiichi Sankyo outside the submitted work. Dr. Suzuki received personal fees from Toa Eiyo, Asahi Kasei, Daiichi Sankyo, Pfizer, Eisai, Nippon Shinyaku, Celltrion Healthcare Japan, Otsuka, Sandoz, Tsumura, Nipro, Taiho, Kyowa-Kirin, Nippon Chemiphar, Japan Blood Products Organization, Takeda, and Nippon Boehringer Ingelheim, as well as grants for their institution from Nippon Kayaku, Asahi Kasei, Chugai, Taiho, Daiichi Sankyo, Japan Blood Products Organization, Mochida, and Sun Pharma outside the submitted work. Dr. Futamura received personal fees from Daiichi Sankyo, Taiho, Chugai, Eisai, Eli Lilly, and Nihon-Kayaku outside the submitted work., (© The author(s).)

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., (© 2023 The Author(s).)

Importance: It is unknown whether olanzapine combined with triplet antemetic therapy is effective for all patients undergoing highly emetogenic chemotherapy. A secondary analysis of randomized clinical trials using olanzapine may provide insight into the effectiveness of olanzapine for chemotherapy-induced nausea and vomiting (CINV), including cisplatin., Objective: To examine the add-on effect of olanzapine according to risk factors for CINV., Design, Setting, and Participants: This preplanned secondary analysis evaluated results of the J-FORCE trial, a large double-blind, placebo-controlled phase 3 randomized clinical trial conducted in Japan from February 9, 2017, to July 18, 2018. Participants were enrolled from 26 participating hospitals across Japan and included patients aged 20 to 75 years who had a malignant tumor and were cisplatin-naive. The efficacy analysis population of the J-FORCE trial was analyzed according to allocation adjustment factors (sex [male or female], age [≥55 years or <55 years], and cisplatin dose [≥70 mg/m2 or <70 mg/m2]) and patient-related risk factors (history of motion sickness, drinking habit [defined as alcoholic drinks consumption in excess of occasional drinking], and history of morning sickness during pregnancy). Statistical analysis was performed from February 18 to April 18, 2020., Interventions: Patients were randomized 1:1 to receive 5 mg of olanzapine or placebo combined with standard triplet antiemetic therapy., Main Outcomes and Measures: The primary end point was complete response (CR, defined as no vomiting and no use of rescue medication) in the delayed phase (24-120 hours after cisplatin-based chemotherapy administration). Secondary end points were CR, complete control, and total control in the acute, delayed, and overall phases for 6 CINV risk factors as well as time to treatment failure. The CR point estimates and 95% CIs of the differences between groups were calculated, and a Mantel-Haenszel test was performed., Results: Of the 705 patients (mean [SD] age, 63.0 [9.2] years; 471 males [66.8%]) included in the efficacy analysis population; 581 patients (82.4%) were 55 years or older, and 526 (74.6%) were treated with a cisplatin dose of 70 mg/m2 or more. Risk difference (RD) for a CR in the delayed phase was significantly greater in the olanzapine group than the placebo group in males (RD, 12.6% [95% CI, 5.0%-20.1%]; P = .001); in females (RD, 14.5% [95% CI, 2.2%-26.3%]; P = .02); in those 55 years or older (RD, 11.1% [95% CI, 3.9%-18.2%]; P = .003) or younger than 55 years (RD, 23.6% [95% CI, 7.3%-38.3%]; P = .005); for a cisplatin dose of 70 mg/m2 or more (RD, 13.5% [95% CI, 5.9%-21.0%]; P < .001); for those without a history of motion sickness (RD, 13.9% [95% CI, 6.9%-20.6%]; P < .001); for those with a drinking habit (RD, 14.9% [95% CI, 6.1%-23.4%]; P = .001) or without a drinking habit (RD, 12.0% [95% CI, 2.5%-21.3%]; P = .01); and for those with a history of morning sickness during pregnancy (RD, 27.2% [9.7%-42.6%]; P = .002). In other subgroups, a delayed CR was higher in the olanzapine group than the placebo group, although not significantly higher., Conclusions and Relevance: Results of this study suggest a benefit of using 5 mg of olanzapine plus triplet antiemetic therapy to counter CINV regardless of the presence or absence of risk factors., Trial Registration: University Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000024676.

Background: Association between baseline medications plus neutrophil-to-lymphocyte ratio (NLR) and the effectiveness of immune checkpoint inhibitor (ICI) plus platinum doublet remains unknown, despite several reported prognostic models. We used real-world data to investigate whether baseline medications plus NLR predict survival outcomes in patients with advanced non-small-cell lung cancer (NSCLC) receiving ICI plus platinum doublet. Methods: This multicenter, retrospective, observational study conducted in Japan between December 2018 and March 2021 used real-world data of consecutive patients with advanced NSCLC who received ICI (pembrolizumab or atezolizumab) plus platinum doublet as first-line treatment. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The prognostic score for baseline medications plus NLR was weighted by regression β coefficients and used to categorize patients into good, intermediate, and poor prognoses groups. In addition, time-dependent receiver operating characteristic curve analyses and univariable and multivariable Cox proportional hazards models were constructed. Results: Overall, 241 patients were included. Poor prognosis was significantly associated with worse PFS (hazard ratio [HR]: 1.78; 95% confidence interval [CI]: 1.08-2.94; P = 0.025) and OS (HR: 3.59; 95% CI: 2.05-6.28; P < 0.001) than good prognosis. Harrell's C-index for this prognostic model was 0.648. Conclusions: Baseline medication plus NLR could predict progressively worse survival outcomes in patients with advanced NSCLC receiving ICI plus platinum doublet and could be used as a prognostic index for poor outcomes., Competing Interests: Competing Interests: Ryuji Uozumi received consulting fees from Eisai, Sawai Pharmaceutical, and EPS. Tadanori Sasaki received research grants from Nippon Kayaku, Daiichi Sankyo, Ono Pharmaceutical, and Mochida Pharmaceutical. Ken Maeno received research grants from Boehringer Ingelheim and Eli Lilly and payment for lectures from AstraZeneca, Chugai Pharmaceutical, and Ono Pharmaceutical. Satoshi Oizumi received payment for lectures from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Ono Pharmaceutical, Takeda, Novartis, Eli Lilly, Merck, Merck Sharp & Dohme, Pfizer, Taiho Pharmaceutical, and Nippon Kayaku. Sojiro Kusumoto received payment for lectures from AstraZeneca, Taiho Pharmaceutical, Kracie Pharmaceutical, Chugai Pharmaceutical, and Novartis Pharma KK. Daiya Takai received payment for lectures from Bristol-Myers Squibb, MSD, and Ono Pharmaceutical. Hitoshi Kawazoe received research funding from Eli Lilly. Tomonori Nakamura received research funding from Astellas Pharma, Chugai, Daiichi Sankyo, Kyowa Kirin, Otsuka Pharmaceutical, Sanofi, Sato Pharmaceutical, and Shionogi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The author(s).)

Background: We previously reported that a standardized pharmacist check of medical orders related to the administration criteria of anticancer drugs prior to preparation of injectable anticancer drugs was useful for reducing drug wastage after mixing. To further reduce anticancer drug wastage after preparation, we added a pharmacist check of patients' infection-related condition to the previous protocol and assessed the effectiveness of the modified protocol for reducing injectable anticancer drug wastage., Methods: In addition to the administration criteria of anticancer drugs, patients' infection-related condition, which was based on a body temperature ≥ 37.5 °C or elevated C-reactive protein (CRP) or white blood cell (WBC) count from baseline, was added to pharmacists' checklist of items used previously to prepare injectable anticancer drugs. We retrospectively compared the number, type and cost of anticancer drugs discarded after preparation and the reasons for discarding these drugs between pre- and post-protocol modification., Results: The rate at which anticancer drugs were discarded after preparation was significantly reduced after introducing the modified protocol compared to the original protocol (0.288% [18/6253] vs. 0.095% [6/6331], P = 0.013). Furthermore, the number of cases for which mixed anticancer agents were discarded because of infection decreased from 11 (fever: n = 8; elevated CRP or WBC: n = 3) to one (elevated CRP: n = 1) a year., Conclusions: In addition to the standard administration criteria of anticancer drugs, checking patients' infection-related condition, defined by a body temperature ≥ 37.5 °C or elevated CRP or WBC from baseline, before mixing by the pharmacist is useful for reducing anticancer drug wastage after preparation., (© 2023. The Author(s).)

Background: The association between the effectiveness of capecitabine and the concomitant administration of gastric acid suppressants remains controversial. We aimed to clarify whether the effectiveness of capecitabine is affected by the co-administration of histamine H 2 receptor antagonists (H 2 RAs) in early-stage colorectal cancer (CRC) patients using real-world data. Methods: This multicenter, retrospective, observational study included consecutive patients with stage II-III CRC who received either capecitabine monotherapy or the CapeOX regimen (capecitabine and oxaliplatin) as adjuvant therapy between January 2009 and December 2014 in Japan. Relapse-free survival (RFS) and overall survival were estimated using the Kaplan-Meier method. Additionally, multivariable Cox proportional hazards model, propensity score adjustment, and inverse probability of treatment weighting analyses were performed. Results: In total, 552 patients were included in this study, of which 30 were co-administered H 2 RAs. RFS at five years was 76.7% (95% confidence interval [CI]: 57.2-88.1%) and 79.8% (95% CI: 76.0-83.0%) in the H 2 RA and non-H 2 RA groups, respectively. Multivariable Cox proportional hazards model and propensity score-adjusted analyses showed that the co-administration of H 2 RAs was associated with a poor RFS among those receiving capecitabine monotherapy (hazard ratio [HR], 2.01; 95% CI: 0.86-4.70 and HR, 1.81; 95% CI: 0.77-4.22, respectively). In contrast, these results were inconsistent with the group receiving the CapeOX regimen. Conclusions: The study findings suggest that the co-administration of H 2 RAs may not reduce the effectiveness of capecitabine therapy in patients with early-stage CRC. To confirm this relationship, a prospective study with a pharmacokinetic approach is needed., Competing Interests: Competing Interests: Ryuji Uozumi: Eisai, Sawai Pharmaceutical, EP Croit (H). Hitoshi Kawazoe: Eli Lilly (RF). The other authors have declared that no competing interest exists., (© The author(s).)

Background: The dexamethasone (DEX)-sparing strategy, which limits administration of DEX to day one, is reportedly non-inferior to conventional antiemetic regimens comprising multiple-day DEX. However, the usefulness of the DEX-sparing strategy in triplet antiemetic prophylaxis (neurokinin-1 receptor antagonist [NK1RA] + serotonin receptor antagonist [5HT3RA] + DEX) for carboplatin and moderate emetogenic chemotherapy (MEC) has not been clarified., Patients and Methods: We systematically reviewed randomized controlled trials that examined the efficacy of antiemetics for preventing chemotherapy-induced nausea and vomiting associated with carboplatin and MEC. We conducted a network meta-analysis to compare the antiemesis efficacy of three-day DEX with NK1RA (3-DEX + NK1RA) and one-day DEX with NK1RA (1-DEX + NK1RA). The primary outcome was complete response during the delayed phase (CR-DP). The secondary outcome was no nausea during the delayed phase (NN-DP)., Results: Seventeen trials involving 4534 patients were included. The proportion who experienced CR-DP was 82.5% (95% credible interval [CI], 73.9-88.6) and 73.5% (95% CI, 62.8-80.9) among those who received 3-DEX + NK1RA and 1-DEX + NK1RA, respectively. There was no significant difference between the two regimens. However, 3-DEX + NK1RA tended to be superior to 1-DEX + NK1RA, with an absolute risk difference of 9.0% (95% CI, -2.3 to 21.1) in CR-DP and 24.7% (95% CI: -14.9 to 54.6) in NN-DP. 3-DEX + NK1RA also tended to be superior to 1-DEX + NK1RA in patients who received carboplatin-based chemotherapy, for whom the absolute risk difference was 12.3% (95% CI, -3.2 to 30.7)., Conclusions: Care is needed when administering the DEX-sparing strategy in combination with NK1RA to patients receiving carboplatin and non-carboplatin MEC., (© The Author(s) 2022. Published by Oxford University Press.)

The association between capecitabine efficacy and proton pump inhibitors (PPIs) is controversial. Here, we determined whether co-administration of PPIs affects the real-world effectiveness of capecitabine. This retrospective observational study included consecutive patients with stage II-III colorectal cancer (CRC) who received adjuvant capecitabine monotherapy or CapeOX (capecitabine and oxaliplatin) between January 2009 and December 2014 at nine participating institutions. The primary endpoint was the difference in relapse-free survival (RFS) between patients who received PPIs and those who did not and was estimated using the Kaplan-Meier method. Overall survival (OS) was the secondary endpoint. Multivariable analysis of RFS and OS was performed using a Cox proportional hazards model, propensity score adjustment, and inverse probability of treatment weighting (IPTW) analyses. Data from 606 patients were evaluated, 54 of whom had received a PPI. PPI-treated patients tended to have poorer RFS and OS than patients treated without PPIs. The hazard ratio for RFS with capecitabine monotherapy was 2.48 (95% confidence interval: 1.22-5.07). These results were consistent with sensitivity analyses performed using propensity score adjustment and IPTW methods. Co-administration of PPIs may reduce the effectiveness of capecitabine and negatively impact patients with stage II-III CRC., (© 2022. The Author(s).)

Pembrolizumab, either as a type of monotherapy or in combination with cytotoxic anticancer agents, is effective in the treatment of advanced non-small cell lung cancer (NSCLC). However, the development of cancer cachexia may adversely affect anticancer drug therapy. The present study investigated the effect of cancer cachexia on clinical outcomes in patients with advanced NSCLC who received first-line pembrolizumab. The data of patients with advanced NSCLC receiving first-line monotherapy or combination therapy with pembrolizumab were retrospectively analyzed. The primary endpoint was time to treatment failure (TTF), and the secondary endpoints were overall survival (OS) and incidence of adverse events (AEs). Clinical outcome was compared between patients with and without cancer cachexia. A total of 53 patients were analyzed. Among all patients, median TTF and OS were significantly shorter in patients with cancer cachexia than in those without [TTF: 5.8 vs. 10 months; hazard ratio (HR): 2.13; 95% confidence interval (CI): 1.07-4.24; P=0.016; OS: 12.1 months vs. not reached; HR: 5.85; 95% CI: 2.0-17.1; P=0.001]. In addition, TTF in the pembrolizumab monotherapy group was significantly shorter in patients with cancer cachexia than in those without, but no significant difference was detected in patients receiving pembrolizumab combination therapy. The incidence of AEs did not significantly differ between patients with and without cancer cachexia, except with regard to hypothyroidism. In conclusion, although cancer cachexia is prognostic of a poor outcome in patients with advanced NSCLC who receive first-line pembrolizumab, cancer cachexia might not affect therapeutic efficacy in combination therapy with pembrolizumab and cytotoxic anticancer agents., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Fujii et al.)

Although co-administration of cisplatin (CDDP) and vinorelbine (VNR) has been established as a standard of care adjuvant chemotherapy for non-small cell lung cancer (NSCLC), there is a lack of clinical data on its safety and efficacy in Japanese patients receiving split-dose administration of CDDP. The present study analyzed patients who received CDDP + VNR with split-dose administration of CDDP after undergoing complete resection of NSCLC. Patients received four courses of CDDP (40 mg/m 2 ) and VNR (25 mg/m 2 ) on days 1 and 8, every 3 weeks. There were 27 male and 13 female patients; the mean age was 65 years (range 38-78 years), the postoperative disease staging distribution was IIA/IIB/IIIA: 14/8/18 patients, and histological distribution was adenocarcinoma/squamous cell carcinoma/others: 24/12/4 patients, respectively. Of the 40 patients, 28 (70%) completed the four courses of treatment. The mean total dose administered was 279 mg/m 2 CDDP (87.2%) and 172 mg/m 2 VNR (86%). The major adverse events included Grade (G) 3 or higher neutropenia (80%), G3 phlebitis (5%) and vomiting (2.5%). There was no G2 or higher serum creatinine level elevation, G3 or higher anorexia and nausea, or any treatment-related deaths. The overall completion rate of four courses was 70 and 62.5% for patients aged 70 years and older, whereas the overall percentage of patients that could complete three or more courses was 85 and 87.5% for patients aged 70 years and older. The relapse-free survival rate was 60% at 3 years and 57.5% at 5 years. Overall survival rate was 80% at 3 years and 60% at 5 years. The present study demonstrated the sufficient tolerability, safety and efficacy of combined CDDP + VNR adjuvant chemotherapy with split-dose administration of CDDP, with a low risk of gastrointestinal toxicities or nephrotoxicity., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

Background: Olanzapine has been reported to be an effective antiemetic in patients receiving carboplatin-based chemotherapy. However, the efficacy of a neurokinin-1 receptor antagonist (NK 1 RA) added to olanzapine, a 5-hydroxytryptamine-3 receptor antagonist (5-HT 3 RA), and dexamethasone (DEX) has not been proven. This study aimed to assess the efficacy and safety of NK 1 RA, in combination with three-drug antiemetic regimens containing olanzapine, in preventing nausea and vomiting induced by carboplatin-based chemotherapy., Methods: Data were pooled for 140 patients receiving carboplatin-based chemotherapy from three multicenter, prospective, single-arm, open-label phase II studies that evaluated the efficacy and safety of olanzapine for chemotherapy-induced nausea and vomiting. The propensity score of the co-administration of NK 1 RA was estimated for each patient using a logistic regression model that included age, sex, and carboplatin dose. We analyzed a total of 62 patients, who were treated without NK 1 RA (non-NK 1 RA group: 31 patients) and with NK 1 RA (NK 1 RA group: 31 patients). The patients were selected using propensity score matching., Results: The complete response rate (without emetic episodes or with no administration of rescue medication) in the overall period (0-120 h post carboplatin administration) was 93.5% in the non-NK 1 RA group and 96.8% in the NK 1 RA group, with a difference of -3.2% (95% confidence interval, -18.7% to 10.9%; P = 1.000). In terms of safety, there was no significant difference between the groups in daytime sleepiness and concentration impairment, which are the most worrisome adverse events induced by olanzapine., Conclusions: The findings suggest that antiemetic regimens consisting of olanzapine, 5HT 3 RA, and DEX without NK 1 RA may be a treatment option for patients receiving carboplatin-based chemotherapy., (© 2022. The Author(s).)

Background: The effect of pharmaceutical intervention to treat adverse events on quality of life (QOL) in outpatients receiving cancer chemotherapy is unclear. We investigated whether pharmaceutical intervention provided by pharmacists in collaboration with physicians improves QOL with outpatient cancer chemotherapy., Methods: We conducted a single-center retrospective descriptive study of pharmaceutical intervention for patients receiving outpatient cancer chemotherapy at Gifu University Hospital between September 2017 and July 2020. We assessed patient QOL using the Japanese version of the EuroQol 5 Dimension5 Level (EQ-5D-5L). Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. We compared the EQ-5D-5L utility value and incidence of grade 2 or higher adverse events before and after pharmaceutical intervention., Results: Our analysis included 151 patients who underwent 210 chemotherapy cycles. Pharmaceutical intervention significantly improved patients' EQ-5D-5L utility values from 0.8197 to 0.8603 (P < 0.01). EQ-5D-5L utility values were significantly improved after pharmaceutical intervention for nausea and vomiting (pre-intervention 0.8145, post-intervention 0.8603, P = 0.016), peripheral neuropathy (pre-intervention 0.7798, post-intervention 0.7988, P = 0.032) and pain (pre-intervention 0.7625, post-intervention 0.8197, P = 0.035). Although not statistically significant, the incidence of grade 2 or higher adverse events, including nausea and vomiting, dermopathy, pain, oral mucositis, diarrhea and dysgeusia, tended to be lower post-intervention than pre-intervention., Conclusions: Pharmaceutical intervention by pharmacists in collaboration with physicians may improve QOL in patients undergoing outpatient cancer chemotherapy., (© 2022. The Author(s).)

Introduction: Triple antiemetic therapy with neurokinin-1 receptor antagonist, 5-hydroxytryptamine type 3 receptor antagonist, and dexamethasone has been widely recommended for high emetogenic chemotherapeutic (HEC) agents and regimens, including anthracycline combined with cyclophosphamide (AC). The addition of olanzapine (OLZ) 5 mg or 10 mg to the recommended triple antiemetic therapy has demonstrated superiority in antiemetic efficacy compared with the standard triplet therapy for a cisplatin-based HEC regimen. Although OLZ plus the triple antiemetic treatment may also be effective for patients on an AC-based HEC regimen, no study has investigated its efficacy at a lower dose of 5 mg., Methods and Analysis: To assess whether 5 mg OLZ, as compared with placebo, in combination with triple combination therapy, significantly improves nausea and vomiting, we are conducting a randomised, parallel-group controlled clinical trial with a total of 500 patients at 15 study centres in Japan. The primary outcome is the complete response rate, defined as no emetic episodes and no use of rescue medication during 120 hours after the initiation of chemotherapy. Treatment group comparison for the primary endpoint will be done by using the Cochran-Mantel-Haenszel test., Ethics and Dissemination: The study was approved by the institutional review board of Juntendo University Hospital and relevant approval was obtained from all participating centres. All participants will be required to provide written informed consent. The trial results will be reported at conferences and in peer-reviewed journals., Trial Registration Number: Japan Registry of Clinical Trials (jRCT) jRCT1031200134; protocol date: 30 July 2020, version: 1.3, approval: 25 August 2020., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cancer chemotherapy usually improves clinical outcomes in patients with advanced pancreatic cancer (APC), but can also cause moderate-to-severe adverse events (AEs). We investigated the relationship between moderate-to-severe AEs and quality of life (QOL) in patients with APC who received outpatient chemotherapy., Methods: We recruited APC patients who received outpatient chemotherapy in Gifu University Hospital between September 2017 and December 2018. Adverse events related to chemotherapy were assessed by a pharmacist collaborating with a physician using common terminology criteria for AEs (CTCAE) ver 4.0, and QOL of patients was self-assessed by patients using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L Japanese edition 2). Associations between the EQ-5D-5L utility value and serious AEs were assessed using proportional odds logistic regression., Results: A total of 59 patients who received 475 chemotherapy cycles were included. The proportional odds logistic regression indicated that grade ≥ 2 anorexia, pain and peripheral neuropathy were significantly correlated with a decreased EQ-5D-5L utility value. Pharmaceutical intervention for these AEs significantly improved the patients' EQ-5D-5L utility value., Conclusions: Anorexia, pain and peripheral neuropathy were significantly associated with a decrease in QOL. It is assumed that appropriate pharmaceutical intervention with particular emphasis on these AEs can improve the QOL of pancreatic cancer patients receiving outpatient chemotherapy., (© 2021. The Author(s).)

Background: The efficacy of olanzapine as an antiemetic agent in cancer chemotherapy has been demonstrated. However, few high-quality reports are available on the evaluation of olanzapine's efficacy and safety at a low dose of 5 mg among patients treated with carboplatin regimens. Therefore, in this study, we investigated the efficacy and safety of 5 mg olanzapine for managing nausea and vomiting in cancer patients receiving carboplatin regimens and identified patient-related risk factors for carboplatin regimen-induced nausea and vomiting treated with 5 mg olanzapine., Methods: Data were pooled for 140 patients from three multicenter, prospective, single-arm, open-label phase II studies evaluating the efficacy and safety of olanzapine for managing nausea and vomiting induced by carboplatin-based chemotherapy. Multivariable logistic regression analyses were performed to determine the patient-related risk factors., Results: Regarding the endpoints of carboplatin regimen-induced nausea and vomiting control, the complete response, complete control, and total control rates during the overall study period were 87.9, 86.4, and 72.9%, respectively. No treatment-related adverse events of grade 3 or higher were observed. The multivariable logistic regression models revealed that only younger age was significantly associated with an increased risk of non-total control. Surprisingly, there was no significant difference in CINV control between the patients treated with or without neurokinin-1 receptor antagonist., Conclusions: The findings suggest that antiemetic regimens containing low-dose (5 mg) olanzapine could be effective and safe for patients receiving carboplatin-based chemotherapy., (© 2021. The Author(s).)

Background/aim: To clarify the risk of chemotherapy-induced nausea and vomiting (CINV) with GnP therapy, gemcitabine (GEM) plus nab-paclitaxel (nab-PTX), we compared CINV between GEM and GnP therapy., Patients and Methods: Patients who had received an initial course of GEM and GnP therapy were enrolled. Primary endpoint was the incidence of nausea, and secondary endpoints were the incidence of vomiting and rescue. In addition, the association between nausea and combination therapy with GEM and nab-PTX was evaluated by multivariate logistic regression with adjustment for covariates. All patients received anti-cancer drugs under guideline-consistent, low-risk antiemetic measures., Results: Data from 105 patients were analyzed (GEM group, 44 patients; GnP group, 61 patients). The incidence of nausea, vomiting, and rescue did not significantly differ between the two groups during the acute, delayed or overall periods. The multivariate logistic regression analysis showed that combination therapy with GEM and nab-PTX was not significantly associated with nausea compared to GEM alone., Conclusion: Under guideline-consistent, low-risk antiemetic measures, GnP therapy-induced nausea and vomiting can be controlled similarly to when induced by GEM., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Olanzapine is an inexpensive and durable agent for the treatment of chemotherapy-induced nausea and vomiting and is also superior to neurokinin-1 receptor antagonists in the control of nausea. This study aimed to investigate the efficacy and safety of a low dose of 5 mg olanzapine plus granisetron and dexamethasone for treatment of carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic malignancies., Materials and Methods: We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four centers in Japan. Registered patients were scheduled to receive area under the curve (AUC) ≥5 mg/mL per minute of CBDCA and had never received moderately to highly emetogenic chemotherapy. Patients received olanzapine 5 mg/day orally after supper for 4 days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the overall phase (0-120 hours)., Results: Between February 2018 and June 2020, 51 patients were enrolled, and 50 patients were evaluated. The CR rates in the overall (0-120 hours), acute (0-24 hours), and delayed phases (24-120 hours) were 94.0%, 100%, and 94.0%, respectively. No grade 3 or higher adverse effects of olanzapine were observed., Conclusion: Prophylactic antiemetic therapy with a low dose of 5 mg olanzapine plus granisetron and dexamethasone showed durable efficacy with an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic malignancies receiving an AUC ≥5 mg/mL per minute of CBDCA-based regimen. Clinical trial identification number: UMIN000031267., Implications for Practice: The results of this phase II trial indicated that the prophylactic administration of low-dose of 5 mg olanzapine combined with granisetron and dexamethasone has promising activity with acceptable safety profile in patients with thoracic malignancy receiving high-dose carboplatin chemotherapy., (© 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Due to the increasing complexity of cancer chemotherapy and its associated supportive care, the role of clinical pharmacists in cancer chemotherapy is becoming increasingly more important. The present study evaluated the clinical interventions of a single pharmacist on the adverse events in hospitalized patients with thoracic cancer receiving cancer chemotherapy. A single-center, retrospective study was conducted at the 614-bed, tertiary care Gifu University Hospital. Hospitalized patients with thoracic cancer who received cancer chemotherapy in the respiratory medicine ward between April 2013 and May 2014 were enrolled. One of the two clinical pharmacists in charge was based in the respiratory medicine ward and implemented pharmaceutical care for the patients, including management of adverse events. Patient data were recorded in the electronic medical chart and retrospectively analyzed. A total of 445 patients with thoracic cancer received cancer chemotherapy in the respiratory medicine ward. A total of 152 interventions (101 patients) were performed by the clinical pharmacist prior to the administration of cancer chemotherapy, half of which comprised the addition of drugs to prevent adverse events. A total of 190 patients (39.4%) experienced grade ≥2 non-hematological or grade ≥3 hematological adverse events associated with cancer chemotherapy, and 223 medical interventions for relief of adverse events lowered the incidence of grade ≥2 non-hematological or grade ≥3 hematological adverse events to 17.8%. Of these, 45.3 and 7.5% of medical interventions for non-hematological and hematological adverse events, respectively, were implemented based on the pharmacist's recommendations. These findings revealed the marked contribution of a single clinical pharmacist in the respiratory medicine ward to the prevention and relief of adverse events in hospitalized patients with thoracic cancer receiving cancer chemotherapy., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021, Spandidos Publications.)

Background/aim: We evaluated the efficacy of primary prophylaxis with pegfilgrastim (PEG) for febrile neutropenia (FN) in small cell lung cancer (SCLC) patients receiving amrubicin (AMR)., Patients and Methods: A retrospective cohort study was conducted in patients with SCLC receiving AMR as second-line therapy., Results: A total of 33 patients were treated with AMR (no PEG group), while 13 patients were treated with AMR plus prophylactic administration of PEG (PEG group). The severity of neutropenia was significantly reduced in the PEG group compared to the no PEG group (p=0.02). The incidence of FN in the no PEG and PEG groups was 27.3% and 7.7%, respectively. The time to development of FN tended to be longer in the PEG group compared to the no PEG group (p=0.132)., Conclusion: Primary prophylaxis with PEG may be beneficial in reducing the risk of FN in patients with SCLC receiving AMR., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Delayed chemotherapy-induced nausea and vomiting (CINV) is not well controlled in colorectal cancer (CRC) patients undergoing oxaliplatin (L-OHP)-based chemotherapy. Whether neurokinin-1 receptor antagonist addition to a first-generation 5HT 3 antagonist (1st 5-HT 3 RA) and dexamethasone (DEX) is beneficial to these patients remains controversial. Furthermore, whether palonosetron (PALO) or aprepitant (APR) is more effective in controlling delayed CINV is unclear. We, therefore, investigated whether PALO+DEX or 1st 5-HT 3 RA+DEX+APR was more effective in controlling delayed CINV, and the risk factors for delayed CINV, in CRC patients undergoing L-OHP-based chemotherapy. Data were pooled from two prospective observational Japanese studies and a phase III trial to compare CINV incidence between the PALO + DEX (PALO) and 5-HT 3 RA+DEX+APR (APR) groups by propensity score-matched analysis. CINV risk factors were identified using logistic regression models. The CINV incidence was higher in the PALO group than in the APR group. Logistic regression analysis revealed alcohol consumption, motion sickness, and the PALO+DEX regimen as independent risk factors for delayed nausea, and female sex and the PALO+DEX regimen as those for delayed vomiting. Compared with prophylactic PALO + DEX, 1st 5-HT 3 RA+DEX+APR was more effective in controlling delayed CINV. Thus, CRC patients receiving L-OHP-based chemotherapy should be treated with three antiemetics, including APR., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Patients with lung cancer who are treated with carboplatin-based chemotherapy regimens often experience chemotherapy-induced nausea and vomiting (CINV). However, knowledge on the effect of regimen and cofactors on the risk of CINV is limited. This study aimed to analyze and compare the incidence of CINV between lung cancer patients undergoing carboplatin plus pemetrexed (CBDCA+PEM) and those undergoing carboplatin plus paclitaxel (CBDCA+PTX) chemotherapy., Methods: Pooled data of 240 patients from two prospective observational studies were compared using propensity score matching. Separate multivariate logistic regression analyses were used to identify risk factors for nausea and vomiting following chemotherapy., Results: Delayed nausea was significantly more common in patients treated with CBDCA+PEM than in those treated with CBDCA+PTX (51.1% vs. 36.2%, P = 0.04), but the incidence of vomiting did not significantly differ between the two groups (23.4% vs. 14.9%, P = 0.14). The occurrence of CINV peaked on day 4 in the CBDCA+PTX group and on day 5 in the CBDCA+PEM group. Multivariate analysis showed that female sex, younger age, and CBDCA+PEM regimen were independent risk factors for delayed nausea, while female sex was an independent risk factor for delayed vomiting., Conclusions: The CBDCA + PEM regimen has a higher risk of causing delayed nausea than the CBDCA + PTX regimen, and aggressive antiemetic prophylaxis should be offered to patients treated with CBDCA + PEM.

Background/aim: We compared the efficacy and safety of second-line FOLFIRI with bevacizumab (Bmab) or aflibercept (AFL) in patients with unresectable metastatic colorectal cancer (mCRC) to clarify selection criteria for anti-angiogenic agents., Patients and Methods: The subjects were patients with mCRC who received second-line FOLFIRI in combination with Bmab or AFL. The primary endpoint was median overall survival (OS). Secondary endpoints were median time to treatment failure (TTF), overall response rate (ORR) and incidence of adverse events., Results: Data from 26 patients in the Bmab group and 19 in the AFL group were analyzed. Median OS was slightly longer in the AFL group compared to the Bmab group, whereas median TTF was similar. ORR tended to be higher in the AFL group. The incidence of ≥grade 2 diarrhea and proteinuria was significantly higher in the AFL group than the Bmab group., Conclusion: In patients given combination treatment with FOLFIRI for second-line treatment of mCRC, AFL can increase response rates compared to Bmab, which may contribute to longer survival., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Dexamethasone (DEX) is administered for multiple days to prevent chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy (HEC); however, its notorious side effects have been widely reported. Although our multicentre randomised double-blind comparative study verified non-inferiority of sparing DEX after day 2 of chemotherapy when combined with neurokinin-1 receptor antagonist (NK1-RA) and palonosetron (Palo) for patients receiving HEC regimen, DEX sparing was not non-inferior in patients receiving cisplatin (CDDP)-based HEC regimens in subgroup analysis. Recently, the efficacy of the addition of olanzapine (OLZ) to standard triple antiemetic therapy on HEC has been demonstrated by several phase III trials. This study aims to confirm non-inferiority of DEX sparing when it is combined with NK-1RA, Palo and OLZ in patients receiving CDDP-based HEC regimens., Methods and Analysis: This is a randomised, double-blind, phase III trial. Patients who are scheduled to receive CDDP ≥50 mg/m 2 as initial chemotherapy are eligible. Patients are randomly assigned to receive either DEX on days 1-4 or DEX on day 1 combined with NK1-RA, Palo and OLZ (5 mg). The primary endpoint is complete response (CR) rate, defined as no emesis and no rescue medications during the delayed phase (24-120 hours post-CDDP administration). The non-inferiority margin is set at -15.0%. We assume that CR rates would be 75% in both arms. Two hundred and sixty-two patients are required for at least 80% power to confirm non-inferiority at a one-sided significance level of 2.5%. After considering the possibility of attrition, we set our final required sample size of 280., Ethics and Dissemination: The institutional review board approved the study protocol at each of the participating centres. The trial result will be presented at international conferences and published in peer-reviewed journals., Trial Registration Number: UMIN000032269., Competing Interests: Competing interests: NI has received honoraria from Takeda Pharma CO., Ltd, Eli Lilly, Japan, Ono Pharma CO., Ltd, and Daiichi Sankyo Company. Author HA has received grant from Taiho, Chugai and Nippon Kayaku; personal fees from Novartis, Sanofi, Ono, Kyowa Kirin and Takeda. TY has received grant and personal fees from Ono Pharmaceutical Co., Ltd. TEN has received grant and personal fee from Taiho Pharmaceutical Co., Chugai Pharmaceutical Co., Takeda Pharmaceutical Co., Sanofi K.K., Daiichi Sankyo Co., Eli Lilly Japan K.K., Nippon Kayaku Co., Ono Pharmaceutical Co. and MSD K.K.; personal fees from Mochida Pharmaceutical, Celltrion Healthcare Japan, Merck Serono Co., Sawai Pharmaceutical Co., Bayer Yakuhin, Bristol-Myers Squibb, Teijin Pharma, Pfizer Japan Inc., Novartis Japan, Yakult Honsha Co. and Nipro Co; grant from Astellas Pharma Inc., Sumitomo Dainippon Pharma Co., Eisai Co and Solasia Pharma K.K. The other authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aim: Nivolumab is effective against advanced gastric cancer (AGC) refractory to or in patients intolerant of standard chemotherapy. This study was designed to clarify the impact of cancer cachexia in patients with AGC who received nivolumab., Patients and Methods: We recruited AGC patients who were treated with nivolumab from October 2017 to December 2019. Clinical outcomes were compared between patients with and without cancer cachexia at the start of nivolumab. Cancer cachexia was defined as weight loss >5%; weight loss >2% and body mass index (BMI) <20; or sarcopenia and BMI <20. Primary endpoints were median overall survival (OS) and median time to treatment failure (TTF), while secondary endpoints were overall response rate (ORR) and incidence of adverse events., Results: The study enrolled 44 patients. Median OS and TTF were significantly shorter in patients with cancer cachexia than in those without cancer cachexia (OS: 6.6 vs. 2.3 months; HR=2.65; 95%CI=1.28-5.49; p=0.008, TTF: 2.6 vs. 1.9 months; HR=2.17; 95%CI=1.09-4.32, p=0.027). On Cox proportional hazards analysis, cancer cachexia was significantly associated with shorter OS. The incidence of adverse events did not differ between the two groups. Nivolumab was associated with better OS and TTF outcomes in AGC patients without cachexia than in those with cachexia, albeit there was no difference in the incidence of adverse events., Conclusion: Cancer cachexia may be associated with worse clinical outcomes in patients with AGC treated with nivolumab., (Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The effect of renal dysfunction on the toxicity and efficacy of oxaliplatin remains unclear. We investigated the association between creatinine clearance (Ccr), a marker of renal function, and the toxicity and efficacy of oxaliplatin in patients with metastatic colorectal cancer (mCRC)., Patients and Methods: Patients with mCRC who received oxaliplatin-based chemotherapy as first-line treatment were included in this study. Primary outcome was peripheral neuropathy (Grade ≥2), while secondary outcomes included neutropenia (Grade ≥3), thrombocytopenia (Grade ≥2) and overall survival (OS)., Results: A total of 145 patients with mCRC were eligible. Incidence rates of peripheral neuropathy (Grade ≥2), neutropenia (Grade ≥3) and thrombocytopenia (Grade ≥2) were 30.3%, 37.2% and 16.6%, respectively, and median OS was 29.1 months. Cox proportional hazards analysis indicated that there was no significant relationship between Ccr and any adverse event, or between Ccr and OS., Conclusion: Dose reduction of oxaliplatin based on Ccr is not recommended in patients with mCRC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: TAS-102 is effective for treating patients with metastatic colorectal cancer (mCRC). This study determined whether combining bevacizumab (Bmab) with TAS-102 improves clinical outcomes in refractory mCRC., Patients and Methods: We retrospectively analyzed data from Japanese patients with refractory mCRC who received TAS-102 (35 mg/m 2 , twice a day) with (T-B group) or without Bmab (TAS-102 monotherapy; T group) between July 2014 and December 2018. The primary endpoint was median overall survival (OS), and secondary endpoints were median time to treatment failure, overall response rate, and the incidence of adverse events. Clinical outcomes were compared using propensity score matched analysis., Results: Data from 57 patients were analyzed (T-B group: 21 patients, T group: 36 patients). Median OS was significantly longer in the T-B group than the T group (14.4 months vs. 4.5 months, p < .001). Cox proportional hazard analysis showed that combination therapy with Bmab was significantly correlated with OS. Propensity score matched analysis confirmed that the median OS was significantly longer in the T-B group than the T group (14.4 months vs. 6.1 months, p = .006) and that there was a significant correlation between Bmab and OS. The incidence of hypertension (grade ≥2) as an adverse event was significantly higher in the T-B group than the T group (23.8% vs. 0.0%, p = .005), whereas other adverse events were comparable between the two groups., Conclusion: Treatment with Bmab in combination with TAS-102 is significantly associated with improved clinical outcomes in patients with mCRC refractory to standard therapies., Implications for Practice: Combining bevacizumab (Bmab) with TAS-102 significantly improved overall survival and several prognostic indicators in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, with manageable toxicities. Treatment with Bmab in combination with TAS-102 is significantly associated with improved clinical outcomes in patients with mCRC., (© 2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Background: We previously reported the results of a prospective study of chemotherapy-induced nausea and vomiting (CINV) in a cohort of patients who received carboplatin-based chemotherapy and were selected from a nationwide registry of those scheduled for moderately (MEC) or highly emetogenic chemotherapy (HEC) by the CINV Study Group of Japan. Of 1,910 previously registered patients (HEC: 1,195; MEC: 715), 400 patients received carboplatin-based chemotherapy. The frequency of CINV was determined, and the risk factors for CINV were assessed., Materials and Methods: CINV data were collected from 7-day diaries. Risk factors for CINV were identified using logistic regression models., Results: Of 400 patients scheduled for carboplatin-based chemotherapy, 267 patients received two antiemetics (5-hydroxytryptamine-3 receptor antagonist [5-HT 3 RA] and dexamethasone [DEX]), 118 patients received three antiemetics (5-HT 3 RA, DEX, and neurokinin-1 receptor antagonist [NK 1 RA]), and 15 were nonadherent to the treatment. In these patients, the CINV overall, acute, and delayed phase rates of complete response (CR), defined as no vomiting with no rescue medication, were 67.0%, 98.2%, and 67.5%, respectively. The rates of no nausea were 55.6%, 94.0%, and 56.1%, respectively, and those of no vomiting were 81.3%, 99.0%, and 81.8%, respectively. Older age was associated with a decreased non-CR, whereas female sex, history of pregnancy-related emesis, and dual antiemetic therapy were associated with an increased non-CR during the overall period., Conclusion: In a clinical practice setting, in patients who received carboplatin-based chemotherapy, adherence is quite high and appropriate antiemetic prophylaxis requires a triple antiemetic regimen including NK 1 RA., Implications for Practice: For patients receiving carboplatin-based chemotherapy, triple antiemetic therapy with 5-hydroxytryptamine-3 receptor antagonist, dexamethasone, and neurokinin-1 receptor antagonist should be given prophylactically regardless of risk factor status., (© 2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Background/aim: To clarify whether renal dysfunction affects the incidence of adverse events associated with oxaliplatin, the present study was designed to investigate the relationship between creatinine clearance (Ccr) and the incidence of oxaliplatin-related adverse events., Patients and Methods: A total of 287 CRC patients who received the first cycle of oxaliplatin-based chemotherapy were eligible. Adverse events, including nausea, vomiting, neutropenia and thrombocytopenia, were graded, and the relationship between Ccr and the incidence of adverse events was examined using multivariable logistic regression analysis., Results: A multivariable analysis indicated that the incidence of grade ≥2 nausea increased, while the incidence of other adverse events tended to be higher, as the Ccr decreased. Particularly, renal dysfunction (Ccr <60 ml/min) was a significant risk factor for grade ≥2 nausea (p=0.042)., Conclusion: Care should be taken to avoid adverse events associated with oxaliplatin in patients with renal dysfunction., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Adding neurokinin-1 receptor antagonist (NK 1 RA) to 5-hydroxytryptamine-3 receptor antagonist and dexamethasone (DEX) improved carboplatin (CBDCA)-induced chemotherapy-induced nausea and vomiting (CINV) in patients with thoracic cancer. NK 1 RAs with high-drug cost are raising medical expenses. Olanzapine (OLZ) is less expensive and can be expected to have an excellent effect on CINV. This phase II trial aimed at evaluating the efficacy and safety of 5 mg OLZ plus granisetron (GRN) and DEX in CBDCA combination therapy with area under curve (AUC) ≥5 mg/mL/min for the prevention of nausea and vomiting in patients with thoracic cancer., Methods and Analysis: This is an open-label, single-arm, multicentre, phase II trial. Patients who receive CBDCA-based therapies (AUC ≥5) and have never been administered moderate to high emetogenic chemotherapy will be enrolled. All patients will receive a combination of GRN, DEX and OLZ. The primary endpoint is complete response (CR) rate, defined as the absence of emetic episodes and no use of rescue medication for 120 hours after the initiation of CBDCA. Forty-eight patients are required based on our hypothesis that this regimen can improve CR rate from 65% (null hypothesis) to 80% (alternative hypothesis) with a one-sided type I error of 0.1 and a power of 0.8. We set the target sample size at 50 considering dropouts., Ethics and Dissemination: The study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals., Trial Registration Number: UMIN000031267., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)