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Winnie Yeo,1 Nicole TY Ngai,1 Christopher CH Yip,1 Frankie KF Mo,1 Victoria A Yeo,1 Jonathan WH Ko,1 Leung V Li,1 Thomas KH Lau,1 Kwai Tung Lai,1 Elizabeth Pang,1 Claudia HW Yip,1 Horatio L Yeo,1 Carol Chi Hei Kwok,2 Stephanie WY Ko,1 Alex Molassiotis3 1Department of Clinical Oncology, Prince of Wales Hospital, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, People’s Republic of China; 2Department of Clinical Oncology, Princess Margaret Hospital, Kowloon, Hong Kong, People’s Republic of China; 3School of Nursing, The Hong Kong Polytechnic University, Hong KongCorrespondence: Winnie Yeo, Department of Clinical Oncology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, People’s Republic of China, Email winnieyeo@cuhk.edu.hkPurpose: Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified in previous studies, only a few studies have evaluated the risk factors associated with contemporary antiemetic prophylaxis, including olanzapine/aprepitant- or NEPA-containing regimens. This study aimed to identify the risk factors associated with CINV development in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide chemotherapy.Methods: Data from 304 patients enrolled in 3 previously reported prospective antiemetic studies were included. Multivariate logistic regression models were used to predict risk factors associated with CINV occurrence. Additionally, the likelihood of treatment failure in relation to the number of risk factors in individual patients was evaluated.Results: Multivariate analysis of the entire study group revealed that obesity status (defined as body mass index/= 25.0 kg/m2) and the use of olanzapine/aprepitant- or NEPA-containing anti-emetic regimens were associated with a high likelihood, while a history of motion sickness was associated with a lower likelihood, complete response (CR), and “no nausea” in the overall phase. A history of vomiting during pregnancy was also associated with a lower likelihood of an overall CR. Patients with an increasing number of risk factors had a higher likelihood of treatment failure and shorter time to first vomiting. Those who did not achieve CR and “no nausea” in the first cycle were less likely to achieve these parameters in the subsequent cycle of chemotherapy.Conclusion: The present study confirmed previously reported risk factors for CINV in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide. Further optimization of CINV control is required for patients with identifiable risk factors; olanzapine/aprepitant- or NEPA- containing prophylaxis are the preferred contemporary anti-emetics regimens for Chinese breast cancer patients undergoing doxorubicin and cyclophosphamide chemotherapy.Keywords: cytotoxic, nausea and vomiting, olanzapine, aprepitant, NEPA

Purpose: We investigated the intensity and duration of nausea as well as its impact on health-related quality of life among cisplatin-treated patients who participated in a study of dexamethasone (DEX)-sparing regimens based on NEPA (netupitant/palonosetron). Methods: This retrospective analysis included chemo-naive patients from a trial evaluating non-inferiority of DEX on day 1 (DEX1 arm) combined with NEPA, compared with the same regimen with DEX administered on days 1–4 (DEX4; reference arm) following cisplatin (≥ 70 mg/m2) administration. Nausea intensity was self-rated using a four-point Likert scale. Extended nausea duration was considered ≥ 3 days within the 5 days post-chemotherapy. Patients completed the Functional Living Index-Emesis (FLIE) questionnaire on day 6. Results: In the DEX1 arm, more patients (20/76) experienced acute nausea, influencing the outcome of delayed nausea (38/76). During days 1 to 5, 51.3% (39/76) and 39.5% (30/76) of patients experienced nausea in the DEX1 and DEX4 arms, respectively (P = 0.192). Of these, 43.6% and 60% reported moderate-to-severe nausea, respectively, in the DEX1 and DEX4 arms (P = 0.200), while 74.4% and 56.7% of patients experienced extended nausea duration (P = 0.122). Similar between-arm rates of nauseated patients reported an impact on daily life (79.5% vs. 70%; P = 0.408). In analyses stratified for antiemetic regimen, moderate-to-severe nausea or extended nausea duration was associated with an impact on daily life (P ≤ 0.001). Conclusion: Despite the higher incidence, there was no suggestion of any strong adverse effect of NEPA plus single-dose DEX on the characteristics of nausea as well as its impact on daily life in patients with cisplatin-induced nausea. Further prospective controlled study is warranted. Trial registration: ClinicalTrials.gov identifier: NCT04201769. Registration date: 17/12/2019. [ABSTRACT FROM AUTHOR]

Background: Highly emetogenic chemotherapy (HEC) is known to induce nausea and vomiting (CINV) in approximately 90% of cancer patients undergoing this regimen unless proper prophylactic antiemetics are administered. This study aimed to analyze the use of a three-drug prophylactic antiemetic regimen during the first cycle of chemotherapy and assess the compliance rate with the National Comprehensive Cancer Network (NCCN) guidelines. Methods: This retrospective study utilized data from the National Inpatient Sample database from 2016 to 2020 provided by the Health Insurance Review and Assessment Service. The claims data encompassed 10 to 13% of inpatients admitted at least once each year. Patients with solid cancers treated with two HEC regimens, namely anthracycline + cyclophosphamide (AC) and cisplatin-based regimens, were selected as the study population. We evaluated the use of a three-drug prophylactic antiemetic regimen, including a neurokinin-1 receptor antagonist, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone and compliance with the NCCN guidelines. Multiple logistic regression was conducted to estimate the influence of variables on guideline adherence. Results: A total of 3119 patients were included in the analysis. The overall compliance rate with the NCCN guidelines for prophylactic antiemetics was 74.3%, with higher rates observed in the AC group (87.9%) and lower rates in the cisplatin group (60.4%). The AC group had a 6.37 times higher likelihood of receiving guideline-adherent antiemetics than the cisplatin group. Further analysis revealed that, compared to 2016, the probability of complying with the guidelines in 2019 and 2020 was 0.72 times and 0.76 times lower, respectively. Conclusion: This study showed that a considerable proportion of HEC-treated patients received guideline-adherent antiemetic therapies. However, given the variations in adherence rates between different chemotherapy regimens (AC vs. cisplatin), efforts to improve adherence and optimize antiemetic treatment remain essential for providing the best possible care for patients experiencing CINV. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced nausea and vomiting is a common problem during cancer treatment, especially in breast cancer patients with anthracycline/cyclophosphamide (ас) chemotherapy. Netupitant/palonosetron (NEPA; Akynzeo®) is a fixed-dose combination of two drugs (netupitant, a neurokinin 1 receptor antagonist; and palonosetron, a serotonin 3 receptor antagonist) which target two diferent signalling pathways involved in the induction of vomiting. Approved for use in the prevention of acute and delayed chemotherapy-induced nausea and vomiting in adults, netupitant/palonosetron is given orally or via intravenous infusion as a single dose prior to chemotherapy. In clinical trials, high proportions of patients who received netupitant/palonosetron (used in combination with the corticosteroid dexamethasone) prior to chemotherapy reported no vomiting, no requirement for rescue medication, and no signifcant nausea in the 5 days post chemotherapy. Both the oral and intravenous formulations of the drug combination are well tolerated. Thus, netupitant/palonosetron is a simple, convenient and efective drug combination for the prevention of acute and delayed xhemotherapy-induced nausea and vomiting in patients receiving chemotherapy that has a moderate to high emetogenic potential.

Abstract Introduction Non‐inferiority of NEPA (fixed combination of NK1 receptor antagonist (RA), netupitant, and 5‐HT3RA, palonosetron) versus an aprepitant regimen was previously shown in a pragmatic study in patients receiving anthracycline cyclophosphamide (AC) and non‐AC moderately emetogenic chemotherapy (MEC). In the MEC group a numerically higher complete response (CR: no emesis, no rescue) rate was seen for NEPA during the overall 0–120 h phase (NEPA 76.1% vs. 63.1% aprepitant). As NEPA exhibits long‐lasting efficacy, this study evaluated a prolonged period up to 144 h, beyond the traditional 120 h post‐chemotherapy. In this post‐hoc analysis we explore the comparative efficacy of NEPA versus the aprepitant regimen in the MEC group up to 144 h, while also assessing the impact of risk factors on CINV prevention. Methods This was a pragmatic, multicenter, randomized, prospective study. Oral NEPA was administered as a single dose on day 1, while aprepitant was given on days 1–3 + ondansetron on day 1; all patients were to receive dexamethasone on days 1–4. Patients were chemotherapy‐naïve and receiving MEC, with a subset evaluation of those with a risk factor for developing CINV (i.e., female, male

Many patients with various localizations of malignant neoplasms require therapy aimed at preventing or reducing the manifestations of nausea and vomiting induced by anticancer pharmacotherapy. New drugs to prevent the development of complications of chemotherapy are critical to improve the quality of life of patients and their adherence to therapy. Palonosetron, a new generation 5-HT3 receptor antagonist, has a long half-life (up to 40 hours) and a 30-fold higher affinity for 5-HT3 receptors compared to previous generations of 5-HT3 receptor antagonists. Clinical studies have shown the ability of palonosetron in combination with dexamethasone and, if indicated, neurokinin antagonists to effectively prevent the development of nausea and vomiting during single- and multi-day cycles of chemotherapy for both solid tumors and hematological diseases, including high-dose chemotherapy, in preparation for transplantation of auto- and allogeneic stem cells. The innovative oral drug Akynzeo is currently available for use in clinical practice, which includes 2 highly selective NK1 and 5-HT3 receptor antagonists in fixed doses. The drug prevents induced nausea and vomiting during moderate and highly emetogenic chemotherapy in more than 90 % of cases, both in the acute and delayed phases.

Introduction: Non‐inferiority of NEPA (fixed combination of NK1 receptor antagonist (RA), netupitant, and 5‐HT3RA, palonosetron) versus an aprepitant regimen was previously shown in a pragmatic study in patients receiving anthracycline cyclophosphamide (AC) and non‐AC moderately emetogenic chemotherapy (MEC). In the MEC group a numerically higher complete response (CR: no emesis, no rescue) rate was seen for NEPA during the overall 0–120 h phase (NEPA 76.1% vs. 63.1% aprepitant). As NEPA exhibits long‐lasting efficacy, this study evaluated a prolonged period up to 144 h, beyond the traditional 120 h post‐chemotherapy. In this post‐hoc analysis we explore the comparative efficacy of NEPA versus the aprepitant regimen in the MEC group up to 144 h, while also assessing the impact of risk factors on CINV prevention. Methods: This was a pragmatic, multicenter, randomized, prospective study. Oral NEPA was administered as a single dose on day 1, while aprepitant was given on days 1–3 + ondansetron on day 1; all patients were to receive dexamethasone on days 1–4. Patients were chemotherapy‐naïve and receiving MEC, with a subset evaluation of those with a risk factor for developing CINV (i.e., female, male <60 years, male ≥60 years who received carboplatin, or male ≥60 years with anxiety). CR rates were compared during the extended overall (0–144 h) phase. Results: The MEC group included 211 patients; of these 181 were in the risk factor subset. Significantly higher CR rates were seen for NEPA than aprepitant during the extended overall phase for the total MEC group (NEPA 77.1%, aprepitant 57.8%, p = 0.003) and also in the subset of patients with CINV risk factors (NEPA 73.9%, aprepitant 56.2%, p = 0.012). Conclusion: A single dose of NEPA, administered on day 1 only, was more effective than a 3‐day aprepitant regimen in preventing CINV for an extended duration in patients receiving MEC and in those with emetic risk factors. [ABSTRACT FROM AUTHOR]

Aims: This investigation aimed to determine the effect of different intensities of training on non-exercise physical activity (NEPA) and estimated thermogenesis (NEAT) from a 1-year exercise randomized controlled trial (RCT) in individuals with type 2 diabetes mellitus (T2DM) on non-training days. Additionally, changes in NEPA and estimated NEAT in those who failed (low-responders) or succeeded (high-responders) in attaining exercise-derived clinically meaningful reductions in body weight (BW) and fat mass (FM) (i.e., 6% for FM and 3% for BW) was assessed. Methods: Individuals with T2DM (n = 80) were enrolled in a RCT with three groups: resistance training combined with moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) and a control group. Of the 80 participants, 56 (completed data) were considered for this secondary analysis. NEPA and estimated NEAT were obtained by accelerometry and body composition through dual-energy X-ray absorptiometry. Results: After adjustments, no time*group interactions were found for estimated NEAT in the MICT (β = − 5.33, p = 0.366) and HIIT (β = − 5.70, p = 0.283), as well as for NEPA in the MICT (β = − 452.83, p = 0.833) and HIIT (β = − 2770.76, p = 0.201), when compared to controls. No compensatory changes in NEPA and estimated NEAT were observed when considering both low-responders and high-responders to FM and BW when compared to controls. Conclusions: Both MICT and HIIT did not result in any compensatory changes in estimated NEAT and NEPA with the intervention on non-training days. Moreover, no changes in estimated NEAT and NEPA were found when categorizing our participants as low-responders and high-responders to FM and BW when compared to controls. Trial registration clinicaltrials.gov ID. NCT03144505. [ABSTRACT FROM AUTHOR]

Environmental impact assessment (EIA) procedures required in the United States and many other countries are often highlighted as a major hindrance to timely and efficient deployment of critical infrastructure projects. Under the U.S. National Environmental Policy Act, a more extensive environmental impact statement (EIS) review can take several more years and cost much more than a succinct environmental assessment (EA). This not only affects the project in question, but also likely informs how—or whether—additional projects are pursued. Thus, understanding key predictors of the EA versus EIS choice sheds light on supply‐side considerations affecting infrastructure deficits. Using the case of NEPA reviews conducted for 244 transmission line projects between 2005 and 2018 by two U.S. federal agencies in the western United States, the Bureau of Land Management (BLM) and Department of Energy (DOE), this addresses the following question: What project features most predict whether EA or an EIS is used to assess a transmission line project? Drawing upon NEPA assessment guidance and agency NEPA records, we use a regression classification tree to analyze how protocols and project attributes relate to assessment choice. The result is essentially a null finding: transmission line length is by far the most important predictor of whether a project receives an extensive EIS or a shorter EA, with little predictive value provided by other attributes. While absolute project size undoubtedly influences impacts, the lack of further differentiation in what predicts use of EISs versus EAs suggests assessment does not simply respond to project details but also shapes proposal and design choices beforehand. [ABSTRACT FROM AUTHOR]

AimTo assess the efficacy of oral NEPA (netupitant-palonosetron 300/0.50 mg) over multiple chemotherapy cycles.MethodsTwo randomized phase III studies evaluated a single dose of oral NEPA given on day 1 in chemotherapy-naive patients receiving anthracycline-cyclophosphamide (AC)-based (Study 1) or highly (HEC)/moderately (MEC) emetogenic chemotherapy (safety Study 2). Oral NEPA was compared with oral palonosetron 0.50 mg (Study 1) or oral aprepitant 125 mg day 1, 80 mg days 2-3/palonosetron 0.50 mg (Study 2; no formal statistical comparisons). Oral dexamethasone was administered in all treatment groups. Complete response (CR; no emesis/no rescue medication), no emesis, and no significant nausea (NSN) rates during acute (0-24 h) and delayed (>24-120 h) phases of chemotherapy cycles 1-4 in each study were evaluated.ResultsIn Study 1, 1450 patients received 5969 chemotherapy cycles; in Study 2, 412 patients received 1961 chemotherapy cycles. In each study, ≥75% of patients completed 4 or more cycles. In Study 1, oral NEPA was superior to palonosetron in preventing chemotherapy-induced nausea and vomiting (CINV) in the acute and delayed phases of cycle 1, with higher rates of CR (all P

Abstract Background The non-inferiority of dexamethasone (DEX) on day 1, with or without low-dose DEX on days 2 and 3, combined with oral NEPA (netupitant/palonosetron), compared with the guideline-consistent use of DEX was demonstrated in cisplatin. Here, we complete the analysis by assessing the impact of emesis on daily lives of patients receiving DEX-sparing regimens using the Functional Living Index-Emesis (FLIE). Methods Chemotherapy-naïve patients undergoing cisplatin (≥70 mg/m2), were given NEPA and DEX (12 mg) on day 1 and randomized to receive either 1) no further DEX (DEX1), 2) oral DEX (4 mg daily) on days 2–3 (DEX3), or 3) DEX (4 mg twice daily) on days 2–4 (DEX4; control). Patients completed the FLIE questionnaire on day 6 of cycle 1. Endpoints included the FLIE nausea domain, vomiting domain, and overall combined domain scores, as well as the proportion of patients with no impact on daily life (NIDL; overall score > 108). This was a protocol-planned analysis. Results In the DEX1 group, no significant differences were observed in the FLIE nausea score (48.9 [±1.8; SE] vs. 53.7 [±1.5]), vomiting score (56.6 [±1.4] vs. 58.7 [±0.8]) and overall score (105.6 [±2.8] vs.112.4 [±1.9]) versus DEX4 control; similar results were observed in the DEX3 group for nausea score (49.6 [±1.7]), vomiting score (58.2 [±1]) and overall score (107.8 [±2.4]) versus control. There were no significant between-group differences in the proportion of patients reporting NIDL. Conclusion Reducing DEX, when administered with NEPA, does not seem to adversely impact the daily functioning in patients undergoing cisplatin. Trial registration ClinicalTrials.gov NCT04201769 . Registration date: 17/12/2019 - Retrospectively registered.

The study dealt with methods of controlling aphids on some grassy field crops in Nepal. The aphids are considered a dangerous sucking piercing insect because they feed on plant sap and attack all parts of the plant and cause damage to it also transmit different viruses. The insects' spreads in both Egypt and Nepal, where the climatic conditions are similar in both countries, which prompted farmers to use multiple methods to control this insect because of the special importance of the grass field crops and where a large percentage of the population depends on them. There are many ways to control aphids, biologically, chemically, and others. One of the most important methods of combating this insect is integrated pest management (IPM). This controlling strategy depends on the rational use of both physical and mechanical control, chemical and biological control, and organizational and legislative control in a way that achieves the goal of its use and maintains the ecological balance. To accomplish this, it is necessary to persuade farmers to use alternative methods to combat natural enemies, particularly aphids, in addition to planting new pest- and disease-resistant plant varieties, exploiting the available natural resources and exploiting environmental factors to eliminate pests, as well as raising their awareness of the effective time and appropriate time to spray pesticides in the proper way, as well as the precautions to be taken into account when spraying and information related to chemical control, as well as their skill in using other control methods and evaluating these uses in control, especially aphids. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the cost-effectiveness of NEPA, a fixed-dose combination of oral netupitant (300 mg) and palonosetron (0.5 mg), compared to available treatments in Spain after aprepitant generic introduction in the market, and to discuss results in previously performed analyses in different wordwide settings. Methods: A Markov model including three health states, complete protection, complete response at best and incomplete response, was used to evaluate the cost-effectiveness of NEPA versus common treatment options in Spain during 5 days after chemotherapy. Incremental costs including treatment costs and treatment failure management cost as well as incremental effects including quality adjusted life days (QALDs) and emesis-free days were compared between NEPA and the comparator arms. The primary outcomes were cost per avoided emetic event and cost per QALDs gained. Results: NEPA was dominant (more effective and less costly) against aprepitant combined with palonosetron, and fosaprepitant combined with granisetron, while, compared to generic aprepitant plus ondansetron, NEPA showed an incremental cost per avoided emetic event of €33 and cost per QALD gained of €125. Conclusion: By most evaluations, NEPA is a dominant or cost-effective treatment alternative to current antiemetic standards of care in Spain during the first 5 days of chemotherapy treatment in cancer patients, despite the introduction of generics. These results are in line with previously reported analyses throughout different international settings. [ABSTRACT FROM AUTHOR]

Aim: To further evaluate the antiemetic efficacy of single-dose versus multiple-dose dexamethasone (DEX) against nausea and vomiting caused by cisplatin. Materials & methods: Two similar non-inferiority studies were pooled. Patients were randomized to single-day DEX or multiple-day DEX plus palonosetron and neurokinin-1 receptor-antagonists (NK-1RAs). The primary endpoint was complete response (CR; no vomiting and no rescue medication) during the overall phase. Results: The combined analysis included 242 patients. The absolute risk difference between single day versus multi-day DEX for CR was -2% (95% CI, -14 to 9%). Conclusion: Administration of single-dose DEX offers comparable antiemetic control to multiple-day DEX when combined with palonosetron and an NK-1RA in the setting of single-day cisplatin. [ABSTRACT FROM AUTHOR]

Background: The non-inferiority of dexamethasone (DEX) on day 1, with or without low-dose DEX on days 2 and 3, combined with oral NEPA (netupitant/palonosetron), compared with the guideline-consistent use of DEX was demonstrated in cisplatin. Here, we complete the analysis by assessing the impact of emesis on daily lives of patients receiving DEX-sparing regimens using the Functional Living Index-Emesis (FLIE).Methods: Chemotherapy-naïve patients undergoing cisplatin (≥70 mg/m2), were given NEPA and DEX (12 mg) on day 1 and randomized to receive either 1) no further DEX (DEX1), 2) oral DEX (4 mg daily) on days 2-3 (DEX3), or 3) DEX (4 mg twice daily) on days 2-4 (DEX4; control). Patients completed the FLIE questionnaire on day 6 of cycle 1. Endpoints included the FLIE nausea domain, vomiting domain, and overall combined domain scores, as well as the proportion of patients with no impact on daily life (NIDL; overall score > 108). This was a protocol-planned analysis.Results: In the DEX1 group, no significant differences were observed in the FLIE nausea score (48.9 [±1.8; SE] vs. 53.7 [±1.5]), vomiting score (56.6 [±1.4] vs. 58.7 [±0.8]) and overall score (105.6 [±2.8] vs.112.4 [±1.9]) versus DEX4 control; similar results were observed in the DEX3 group for nausea score (49.6 [±1.7]), vomiting score (58.2 [±1]) and overall score (107.8 [±2.4]) versus control. There were no significant between-group differences in the proportion of patients reporting NIDL.Conclusion: Reducing DEX, when administered with NEPA, does not seem to adversely impact the daily functioning in patients undergoing cisplatin.Trial Registration: ClinicalTrials.gov NCT04201769 . Registration date: 17/12/2019 - Retrospectively registered. [ABSTRACT FROM AUTHOR]

Objective: Chemotherapy-induced nausea and vomiting (CINV) are common with doxorubicin-cyclophosphamide (AC) chemotherapy. Recommended antiemetic regimens incorporate neurokinin-1 receptor antagonist (NK1RA), 5-hydroxytryptamine type-3 receptor antagonist (5HT3RA), corticosteroid, and dopamine antagonists. This post-hoc analysis compared results of 3 prospective antiemetic studies conducted among Chinese breast cancer patients who received (neo)adjuvant AC, in order to identify optimal antiemetic prophylaxis. Methods: A total of 304 patients were included: Group 1, ondansetron/dexamethasone (D1); Group 2, aprepitant/ondansetron/dexamethasone (D1); Group 3, aprepitant/ondansetron/dexamethasone (D1–3); Group 4, aprepitant/ondansetron/dexamethasone (D1–3)/olanzapine; and Group 5, netupitant/palonosetron/dexamethasone (D1–3). Antiemetic efficacies of Groups 3, 4, and 5 during cycle 1 of AC were individually compared with Group 1. In addition, emesis outcomes of patients in Groups 3 and 5, and those of Groups 2 and 3, were compared. Results: When comparing efficacies of a historical doublet (5HT3RA/dexamethasone) with triplet antiemetic regimens (NK1RA/5HT3RA/dexamethasone) with/without olanzapine, complete response (CR) percentages and quality of life (QOL) in overall phase of cycle 1 AC were compared between Group 1 and the other groups: Group 1 vs. 3, 41.9% vs. 38.3% (P = 0.6849); Group 1 vs. 4, 41.9% vs. 65.0% (P = 0.0107); and Group 1 vs. 5, 41.9% vs. 60.0% (P = 0.0460). Groups 4 and 5 achieved a better QOL. When comparing netupitant-based (Group 3) with aprepitant-based (Group 5) triplet antiemetics, CR percentages were 38.3% vs. 60.0%, respectively (P = 0.0176); Group 5 achieved a better QOL. When comparing 1 day (Group 2) vs. 3 day (Group 3) dexamethasone, CR percentages were 46.8% and 38.3%, respectively (P = 0.3459); Group 3 had a worse QOL. Conclusions: Aprepitant-containing triplets were non-superior to doublet antiemetics. Netupitant-containing triplets and adding olanzapine to aprepitant-containing triplets were superior to doublets. Netupitant/palonosetron/dexamethasone was superior to aprepitant/ondansetron/dexamethasone. Protracted administration of dexamethasone provided limited additional benefit.

Abstract Background Chemotherapy induced nausea- vomiting (CINV) is considered as the most common, feared and most troublesome side effect of chemotherapy. NEPA (NEtupitant 300 mg + PAlonosetron 0.50 mg) is the first commercially available oral fixed-dose combination (FDC) of two active antiemetic agents in India. The present study was planned to evaluate the effectiveness of NEPA in the real world setting of India. Methods This was a multicentric retrospective study conducted in two centers in India. The data of all chemonaive patients, who were prescribed NEPA was analyzed. Effectiveness i.e. complete response and complete protection in controlling overall, acute and delayed phase was analyzed. Results A total of 329 patients were enrolled in the study. 260 received highly emetogenic chemotherapy (HEC) regimen and 69 received moderately emetogenic chemotherapy (MEC) regimen. Among all the enrolled patients, complete response in acute, delayed and overall phase was 93, 85.71 and 85.41% respectively; and completed protection was 88.44, 81.76 and 80.54% respectively. Those who received HEC regimen, the completed response and complete protection in overall phase was 84.61 and 79.61% respectively and those who received MEC regimen the completed response and complete control in overall phase was 84.05 and 84.05% respectively. Conclusion A single oral dose of NEPA targeting dual pathways showed effective control of nausea-vomiting in patients on the HEC and MEC regimens and had good control over nausea-vomiting in acute, delayed and overall phase of nausea-vomiting.

Introduction: We describe the results of an exploratory analysis performed on the first head-to-head study (JapicCTI-194611) comparing two different intravenous (IV) neurokinin 1 (NK1) receptor antagonists, fosnetupitant and fosaprepitant, in combination with palonosetron (PALO) and dexamethasone (DEX) for the prevention of highly emetogenic chemotherapy (HEC)-induced nausea and vomiting (CINV). This analysis was performed to validate the findings of the primary analysis (previously published) utilizing a last observation carried forward (LOCF) approach for missing values for the efficacy endpoint of complete response (no emetic event and no rescue medication), while also evaluating the time periods encompassing the 0–168-hour (h) "extended overall phase" interval. Methods: Patients scheduled to receive cisplatin-based chemotherapy were randomized 1:1 to fosnetupitant 235 mg or fosaprepitant 150 mg in combination with PALO 0.75 mg and DEX. Complete response rates were calculated and compared (stratified by age category and sex with a Mantel–Haenszel test) during the study's primary overall phase (0–120 h) and during additional time intervals of interest [acute (0–24 h), delayed (24–120 h), extended delayed (> 24–168 h), beyond delayed (120–168 h), and extended overall (0–168 h)]. Results: A total of 785 patients were included (fosnetupitant N = 392, fosaprepitant N = 393). Complete response rates were numerically higher for fosnetupitant versus fosaprepitant for all time intervals and statistically significant for the extended overall phase. Complete response rates for fosnetupitant versus fosaprepitant during the overall, acute, delayed, extended delayed, beyond delayed, and extended overall phases were 75.5% vs. 71.0% (p = 0.1530), 93.9% vs. 92.6% (p = 0.4832), 77.0% vs. 72.8% (p = 0.1682), 74.7% vs. 68.4% (p = 0.0506), 86.7% vs. 81.7% (p = 0.0523), and 73.5% vs. 66.9% (p = 0.0450), respectively. Conclusion: In this exploratory analysis, fosnetupitant appeared to be more effective than fosaprepitant in preventing CINV associated with cisplatin-based HEC during the extended 7-day period following chemotherapy. Infographic: [ABSTRACT FROM AUTHOR]

A right to a healthy environment is neither novel nor extreme. As this Essay posits, this is a propitious moment for exploring why such a right is supported by this Nation’s legal institutions. This Essay walks through those institutions – our Constitution, the common law, as well as Congressional and state efforts to embed a right to a healthy environment into our legal fabric. Those institutions collectively demonstrate how an aspirational right, such as a right to a healthy environment, enjoys sufficient legal currency and is capable of enforcement.

Introduction: In a prospective non-interventional study involving 2,173 patients, we showed that use of the oral fixed combination of netupitant 300 mg and palonosetron 0.5 mg (NEPA) for prevention of chemotherapy (Ctx)-induced nausea and vomiting has beneficial effects on the quality of life (QoL) of patients with various types of cancers receiving highly or moderately emetogenic Ctx. Here, we report on the effects on QoL, effectiveness, and tolerability of NEPA in patients with breast cancer exposed to anthracycline-cyclophosphamide (AC)-based Ctx. Methods: This is a post hoc subanalysis of a prospective non-interventional study in 1,197 patients with breast cancer receiving up to 3 cycles of doxorubicin or epirubicin plus cyclophosphamide and NEPA. NEPA administration was per the summary of product characteristics. Results: In cycle 1 of Ctx, a large proportion of patients (84%) reported "no impact on daily life" (NIDL) due to vomiting; 53% of patients reported NIDL due to nausea. The complete response rate was 86/88/81% in the acute/delayed/overall phase in cycle 1, and NEPA was well tolerated throughout the study. Conclusion: The real-world beneficial effects of NEPA prophylaxis on QoL were confirmed for patients with breast cancer receiving AC. NEPA was effective with a good safety profile in this patient population in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Prevention of chemotherapy-induced nausea and vomiting (CINV) is particularly challenging for patients receiving highly emetogenic preparative regimens before autologous stem cell transplantation (ASCT) due to the daily and continuous emetogenic stimulus of the multiple day chemotherapy. While studies have shown effective prevention of CINV during the conditioning phase with NK1 receptor antagonist (NK1RA)-containing regimens, there have been no studies evaluating antiemetic use during chemomobilization prior to ASCT. Methods: This multicenter, open-label, phase IIa study evaluated the efficacy of every-other-day dosing of NEPA administered during chemomobilization in patients with relapsed-refractory aggressive non-Hodgkin's lymphoma. Eighty-one patients participated. Results: Response rates were 77.8% for complete response (no emesis and no rescue use), 72.8% for complete control (complete response and no more than mild nausea), 86.4% for no emesis, and 82.7% for no rescue use during the overall phase (duration of chemomobilization through 48 h after). NEPA was well tolerated with no treatment-related adverse events reported. Conclusion: NEPA, administered with a simplified every-other-day schedule, show to be very effective in preventing CINV in patients at high risk of CINV undergoing to chemomobilization of hematopoietic stem cells prior to ASCT. [ABSTRACT FROM AUTHOR]

Abstract NEPA is the only fixed combination antiemetic, comprised of an NK1RA (netupitant) and a 5‐HT3RA (palonosetron). In the first head‐to‐head trial to compare NK1RA‐containing regimens, a single oral dose of NEPA was non‐inferior to a 3‐day aprepitant/granisetron (APR/GRAN) regimen for the primary endpoint of overall (0‐120 hours) complete response (no emesis/no rescue). This pre‐specified analysis evaluates the efficacy of NEPA versus APR/GRAN in the subset of Chinese patients in the study. In addition, efficacy in patients at greatest emetic risk receiving high‐dose cisplatin (≥70 mg/m2) was explored. Chemotherapy‐naïve patients with solid tumors in this randomized, double‐blind study received either a single dose of NEPA prior to cisplatin‐based chemotherapy or a 3‐day regimen of APR/GRAN, both with dexamethasone on Days 1‐4. Efficacy was evaluated through complete response, no emesis, and no significant nausea rates during the acute (0‐24 hours), delayed (25‐120 hours) and overall phases as well as individual days post‐chemotherapy, as the daily course of CINV protection is often unstudied. The Chinese subset included 667 patients; of these, 363 (54%) received high‐dose cisplatin. Baseline characteristics were comparable. While response rates were similar for NEPA and APR/GRAN during the acute, delayed and overall phases, significantly fewer NEPA patients experienced breakthrough CINV on individual Days 3‐5 in both the Chinese patients and also in those receiving high‐dose cisplatin. As a fixed oral NK1RA/5HT3RA combination given once/cycle, NEPA is a convenient highly effective prophylactic antiemetic that may offer better protection from CINV than a 3‐day APR/GRAN regimen on Days 3‐5 following highly emetogenic chemotherapy.

Abstract Background NEPA is an oral fixed-dose combination of netupitant, a new highly selective neurokinin-1 receptor antagonist, and palonosetron. This study was conducted to evaluate whether the efficacy of NEPA against chemotherapy-induced nausea and vomiting (CINV) in cycle 1 would be maintained over subsequent chemotherapy cycles in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide (AC). The study also describes the relationship between efficacy on day 1 through 5 (overall period) and control of CINV on day 6 through 21 (very late period) in each cycle. Methods In this multicentre, phase II study, patients received both NEPA and dexamethasone (12 mg intravenously) just before chemotherapy. The primary efficacy endpoint was overall complete response (CR; no emesis and no rescue medication use) in cycle 1. Sustained efficacy was evaluated during the subsequent cycles by calculating the rate of CR in cycles 2–4 and by assessing the probability of sustained CR over multiple cycles. The impact of both overall CR and risk factors for CINV on the control of very late events (vomiting and moderate-to-severe nausea) were also examined. Results Of the 149 patients enrolled in the study, 139 were evaluable for a total of 552 cycles; 97.8% completed all 4 cycles. The proportion of patients with an overall CR was 70.5% (90% CI, 64.1 to 76.9) in cycle 1, and this was maintained in subsequent cycles. The cumulative percentage of patients with a sustained CR over 4 cycles was 53%. NEPA was well tolerated across cycles. In each cycle, patients with CR experienced a significantly better control of very late CINV events than those who experienced no CR. Among the patients with CR, the only predictor for increased likelihood of developing very late CINV was pre-chemotherapy (anticipatory) nausea (adjusted odds ratio = 0.65–0.50 for no CINV events on cycles 3 and 4). Conclusion The high anti-emetic efficacy seen with the NEPA regimen in the first cycle was maintained over multiple cycles of adjuvant AC for breast cancer. Preliminary evidence also suggests that patients achieving a CR during the overall period gain high protection even against very late CINV events in each chemotherapy cycle. Trial registration This trial was retrospectively registered at Clinicaltrials.gov identifier ( NCT03862144 ) on 05/Mar/2019.

Background: Chemotherapy-induced nausea and vomiting (CINV) significantly impacts patient's quality of life and treatment adherence. This study investigated the efficacy of Generic Netupitant and Palonosetron tablets (Nykron) with dexamethasone single dose for CINV prophylaxis in patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). Additionally, this approach aligns with the principles of the SHIELD study (Sparing High Efficacy Intervention for Low Dose Dexamethasone), which focuses on maximizing antiemetic effectiveness while minimizing dexamethasone use., Methodology: This multicenter retrospective study evaluates data from patients who received HEC/MEC and were administered a fixed-dose combination of Generic NEPA (Netupitant 300 mg and Palonosetron 0.5 mg tablets, Nykron combi-pack) along with a single dose of dexamethasone (12 mg/8 mg) before chemotherapy. The data were collected from September 2022 till September 2023. Outcomes measured included complete response (no vomiting and no need for rescue medications), complete protection (no significant nausea (<2.5 cm on VAS), no vomiting, and no use of rescue medication), and complete control (no emetic episodes, no rescue therapy, and no nausea [0 cm on VAS]) during the acute phase (0-24 hours) and delayed phase (24-120 hours) post-chemotherapy., Results: The data of 372 patients was evaluated in which breast cancer was the most common cancer with 223 (59.95%) patients for which doxorubicin and cyclophosphamide (192, 51.61%) was the most administered chemotherapy combination. The second most common cancer was gastrointestinal (GI) cancer with stomach cancer in 47 (12.6%), colorectal cancer in 4 (1%), and pancreatic cancer in 2 (0.54%). A total of 360 (96.8%) patients received an HEC regimen across the cycle, while only 5 (1.3%) received an MEC regimen. The regimen demonstrated exceptional efficacy with a 96.9% overall response rate across all cycles. Complete control rates for acute CINV were 92% and 90% for delayed CINV across chemotherapy cycles. Complete response rates remained consistently high (94%-98%) across all cycles and overall phases. Only 3% of patients experienced anticipatory CINV., Conclusions: This dexamethasone-sparing Generic NEPA regimen showed remarkable efficacy in CINV management for HEC/MEC regimen-receiving patients, maintaining high response rates in both acute and delayed across all cycles. These findings indicate a potential paradigm shift in CINV prophylaxis, necessitating further investigation through prospective, randomized controlled trials to validate long-term safety and efficacy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. ACEAS Ethics Committee issued approval TV/02/07/23. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Reddy et al.)

Aim: In the absence of comparative studies, guidelines consider neurokinin 1 receptor antagonists (RAs) as interchangeable. We evaluated the pooled efficacy from three cisplatin registration trials, each with arms containing netupitant/palonosetron (NEPA), a fixed neurokinin 1 RA (netupitant)/serotonin Type 3 (5-HT3) RA (palonosetron) combination, and an aprepitant (APR) regimen. Materials & methods: Efficacy data were pooled for rates of complete response (CR: no emesis/no rescue medication), complete protection (CR + no significant nausea), total control (CR + no nausea) and no significant nausea during acute (0-24 h), delayed (>24-120 h) and overall (0-120 h) phases post chemotherapy. Results: Among 621 NEPA and 576 APR patients, response rates were similar for the acute phase, and generally favored NEPA during delayed and overall phases. CR rates for NEPA versus APR were 88.4 versus 89.2%, 81.8 versus 76.9% (p < 0.05) and 78.4 versus 75.0% during the acute, delayed and overall phases, respectively. Conclusion: Oral NEPA administered on day 1 was more effective than a 3-day APR regimen in preventing delayed nausea and vomiting associated with cisplatin. [ABSTRACT FROM AUTHOR]

Acting with No Regret: A Twenty-Five Year Retrospective of Marsh v. Oregon Natural Resources Defense Council

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Abstract Aim To assess the efficacy of oral NEPA (netupitant‐palonosetron 300/0.50 mg) over multiple chemotherapy cycles. Methods Two randomized phase III studies evaluated a single dose of oral NEPA given on day 1 in chemotherapy‐naive patients receiving anthracycline‐cyclophosphamide (AC)–based (Study 1) or highly (HEC)/moderately (MEC) emetogenic chemotherapy (safety Study 2). Oral NEPA was compared with oral palonosetron 0.50 mg (Study 1) or oral aprepitant 125 mg day 1, 80 mg days 2‐3/palonosetron 0.50 mg (Study 2; no formal statistical comparisons). Oral dexamethasone was administered in all treatment groups. Complete response (CR; no emesis/no rescue medication), no emesis, and no significant nausea (NSN) rates during acute (0‐24 h) and delayed (>24‐120 h) phases of chemotherapy cycles 1‐4 in each study were evaluated. Results In Study 1, 1450 patients received 5969 chemotherapy cycles; in Study 2, 412 patients received 1961 chemotherapy cycles. In each study, ≥75% of patients completed 4 or more cycles. In Study 1, oral NEPA was superior to palonosetron in preventing chemotherapy‐induced nausea and vomiting (CINV) in the acute and delayed phases of cycle 1, with higher rates of CR (all P

Background: Chemotherapy induced nausea- vomiting (CINV) is considered as the most common, feared and most troublesome side effect of chemotherapy. NEPA (NEtupitant 300 mg + PAlonosetron 0.50 mg) is the first commercially available oral fixed-dose combination (FDC) of two active antiemetic agents in India. The present study was planned to evaluate the effectiveness of NEPA in the real world setting of India.Methods: This was a multicentric retrospective study conducted in two centers in India. The data of all chemonaive patients, who were prescribed NEPA was analyzed. Effectiveness i.e. complete response and complete protection in controlling overall, acute and delayed phase was analyzed.Results: A total of 329 patients were enrolled in the study. 260 received highly emetogenic chemotherapy (HEC) regimen and 69 received moderately emetogenic chemotherapy (MEC) regimen. Among all the enrolled patients, complete response in acute, delayed and overall phase was 93, 85.71 and 85.41% respectively; and completed protection was 88.44, 81.76 and 80.54% respectively. Those who received HEC regimen, the completed response and complete protection in overall phase was 84.61 and 79.61% respectively and those who received MEC regimen the completed response and complete control in overall phase was 84.05 and 84.05% respectively.Conclusion: A single oral dose of NEPA targeting dual pathways showed effective control of nausea-vomiting in patients on the HEC and MEC regimens and had good control over nausea-vomiting in acute, delayed and overall phase of nausea-vomiting. [ABSTRACT FROM AUTHOR]

Purpose: Oral NEPA, the only fixed-combination antiemetic, is composed of the neurokinin-1 receptor antagonist netupitant (300 mg) and the 5-hydroxytryptamine-3 receptor antagonist palonosetron (0.50 mg). This study was conducted to evaluate the pharmacokinetic profile of netupitant and its main metabolites M1 and M3, and palonosetron in Chinese subjects. Oral NEPA tolerability and safety were also analyzed.Methods: This was a single-center, single-dose phase 1 study in healthy, adult Chinese volunteers. Eligible subjects received oral NEPA, and blood samples were collected on day 1 predose and at various time points up until day 10 postdose. Pharmacokinetic parameters were analyzed using noncompartmental methods. For safety assessments, adverse events (AEs) were monitored during the study.Results: In total 18 Chinese healthy volunteers received oral NEPA. Netupitant mean maximum plasma concentration (Cmax) [± standard deviation] of 698 ± 217 ng/mL was reached at 3-6 h, with a mean total exposure (AUC0-inf) of 22,000 ± 4410 h·ng/mL. For palonosetron, a mean Cmax of 1.8 ± 0.252 ng/mL was reached at 2-6 h postadministration, with a mean AUC0-inf of 81.0 ± 14.0 h·ng/mL. The most common treatment-related AEs in > 2 subjects were constipation (n = 9) and tiredness (n = 3). No severe AEs were observed, and no subject withdrew due to AEs.Conclusion: Following single-dose administration of oral NEPA in Chinese subjects, the pharmacokinetic profiles of the NEPA components were mostly similar to those reported previously in Caucasians. NEPA was well tolerated with a safety profile in line with that observed in pivotal trials in Caucasians. [ABSTRACT FROM AUTHOR]