Safety of a short-term infusion of fosnetupitant in patients with gastrointestinal and breast cancer: a prospective study.

BACKGROUND: Fosnetupitant, a neurokinin-1 receptor antagonist, is used to prevent chemotherapy-induced nausea and vomiting (CINV) in patients undergoing highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Previous phase III trials demonstrated the non-inferiority of its 30-minute infusion to fosaprepitant in efficacy and a favorable safety profile. METHODS: This was a single-arm, phase II study to investigate the safety of a 15-minute infusion of fosnetupitant in patients with gastrointestinal and breast cancer. Patients who had received their dose of fosnetupitant in a 30-minute infusion without developing an allergic reaction were eligible and received their next fosnetupitant dose for 15 minutes. The primary endpoint was the incidence of an allergic reaction during the first 15-minutes infusion, and the secondary endpoints were the incidence of injection site reaction (ISR), the incidence of a grade ≥ 3 treatment-related adverse event (TRAE) with fosnetupitant, and complete response (CR) rate. RESULTS: The study period was from February 17, 2023 to June 20, 2023. In an exploratory analysis, medical records from the end of the study period to December 31, 2023 were retrospectively evaluated to assess the time-saving effect and safety of the short-term infusion of fosnetupitant. Fifty-six patients with gastrointestinal and 14 patients with breast cancer were enrolled, one of whom with breast cancer did not receive study treatment at her own request. No allergic reactions occurred during the 15-minutes infusion. Furthermore, there were no allergic reactions across all 280 short-term injections (Table 1). Additionally, no ISR or grade 3 or higher TRAE were reported. The CR rate was 87.0%. CONCLUSION: Short-term infusion of fosnetupitant, administered over 15 minutes, was demonstrated to be safe and effective for patients receiving HEC or MEC (Japan Registry of Clinical Trials Trial ID: jRCT1041220144).

Comparative effectiveness of netupitant-palonosetron plus dexamethasone versus aprepitant-based regimens in mitigating chemotherapy-induced nausea and vomiting: a meta-analysis of randomized controlled trials.

BACKGROUND: Despite guidelines for managing chemotherapy-induced nausea and vomiting (CINV), there remains a need to clarify the optimal use of neurokinin-1 (NK1) receptor antagonists. Comparing the effectiveness of NEPA (netupitant-palonosetron) plus dexamethasone with other NK1 antagonist-based regimens combined with a 5HT3 receptor antagonist and dexamethasone is crucial for informed decision-making and improving patient outcomes. METHODS: We conducted a systematic review of the literature to assess randomized controlled trials (RCTs) comparing the efficacy, safety, and cost-effectiveness of NEPA plus dexamethasone and other NK1 antagonist-based regimens combined with a 5HT3 receptor antagonist and dexamethasone. PubMed, Embase, and the Cochrane Library databases were systematically searched, with the latest update performed in December 2023. Data on patient demographics, chemotherapy regimen characteristics, and outcomes were extracted for meta-analysis using a random-effects model. RESULTS: Seven RCTs were analyzed. NEPA plus dexamethasone showed superior efficacy in achieving complete response in the overall (risk ratio [RR], 1.15; 95% CI, 1.02--1.30) and delayed phases (RR, 1.20; 95% CI, 1.03-1.41) of chemotherapy. It was more effective in controlling nausea (overall phase RR, 1.20; 95% CI, 1.05-1.36; delayed phase RR, 1.21; 95% CI, 1.05-1.40) and reducing rescue therapy use (overall phase RR, 1.45; 95% CI, 1.07-1.95; delayed phase RR, 1.75; 95% CI, 1.10-2.78). Adverse event rates were comparable (RR, 1.03; 95% CI, 0.96-1.10). Subgroup analysis indicated NEPA's particular efficacy in patients receiving moderately emetogenic chemotherapy (RR, 1.31; 95% CI, 1.07-1.60). CONCLUSION: NEPA plus dexamethasone regimens exhibit superior efficacy in preventing CINV, supporting their preferential inclusion in prophylactic treatment protocols. Its effective symptom control, safety profile, and cost-effectiveness endorse NEPA-based regimens as a beneficial option in CINV management.

Effectivity of oral ginger supplementation for chemotherapy induced nausea and vomiting (CINV) in children: A systematic review of clinical trials.

Chemotherapy-induced nausea and vomiting (CINV) affects over 50% of pediatric patients undergoing chemotherapy, a higher proportion than in adults. CINV often occurs despite adequate antiemetic prophylaxis, hampering patients' willingness to continue the chemotherapy regimen. As an ayurvedic medicine, ginger (Zingiber officinale) has an antiemetic effect by inhibiting serotonin in gastrointestinal nerves and as an NK1 antagonist. Therefore, we aimed to review oral ginger supplementation in children with CINV systematically. Systematic searching was performed in June 2023 from Pubmed, Embase, CINAHL, Cochrane, and hand searching. The search consisted of PICO "children chemotherapy", "ginger", and "CINV incidence". We limited the search to only human studies. Studies that meet inclusion and exclusion criteria were included for analysis. Out of 116 studies found with our selection criteria, four were compatible with inclusion and exclusion criteria. Two studies had a small Risk of Bias (RoB), while the others had a high RoB. All studies statistically significantly reduced acute and delayed CINV with the number needed to treat (NNT) 2-4. No adverse effects were reported. However, these studies still had high heterogeneity based on cancer treatment, chemotherapy regimen, ginger dosing, and ginger processing. Ginger has the potential to reduce both the acute and delayed phases of CINV in children. Additional research employing standardized methodologies is recommended to validate this effect.

Central mechanisms of emesis: A role for GDF15.

BACKGROUND: Nausea and emesis are ubiquitously reported medical conditions and often present as treatment side effects along with polymorbidities contributing to detrimental life-threatening outcomes, such as poor nutrition, lower quality of life, and unfavorable patient prognosis. Growth differentiation factor 15 (GDF15) is a stress response cytokine secreted by a wide variety of cell types in response to a broad range of stressors. Circulating GDF15 levels are elevated in a range of medical conditions characterized by cachexia and malaise. In recent years, GDF15 has gained scientific and translational prominence with the discovery that its receptor, GDNF family receptor α-like (GFRAL), is expressed exclusively in the hindbrain. GFRAL activation may results in profound anorexia and body weight loss, effects which have attracted interest for the pharmacological treatment of obesity. PURPOSE: This review highlights compelling emerging evidence indicating that GDF15 causes anorexia through the induction of nausea, emesis, and food aversions, which encourage a perspective on GDF15 system function in physiology and behavior beyond homeostatic energy regulation contexts. This highlights the potential role of GDF15 in the central mediation of nausea and emesis following a variety of physiological, and pathophysiological conditions such as chemotherapy-induced emesis, hyperemesis gravidarum, and cyclic vomiting syndrome.

NHS-Reimbursed Cannabis Flowers for Cancer Palliative Care and the Management of Chemotherapy-Induced Nausea and Vomiting: An Autobiographical Case Report.

Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of cancer treatment, affecting many patients. Cannabinoid agonists, such as nabilone and Δ9-tetrahydrocannabinol (THC), the main psychoactive component of Cannabis sativa L., have shown efficacy as antiemetics. Here, we report the case of Michael Roberts (MR), who we believe is the first British patient reimbursed by the National Health Service (NHS) England for the cost of medicinal cannabis flowers to manage CINV. Medical data were obtained from NHS records and individual funding request (IFR) forms. Patient-reported outcome measures (PROMs) were collected using validated questionnaires as part of the standard of care at the specialized private clinics where the prescription of medicinal cannabis was initiated. The patient presented with rectosigmoid adenocarcinoma with lung metastases. He received FOLFIRI (folinic acid, fluorouracil, and irinotecan) chemotherapy and underwent an emergency Hartmann's procedure with subsequent second-line FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy and lung ablation. MR reported severe nausea and vomiting associated with the initial FOLFIRI treatment. Antiemetics metoclopramide and aprepitant demonstrated moderated efficacy. Antiemetics ondansetron, levomepromazine, and nabilone were associated with intolerable side effects. Inhalation of THC-predominant cannabis flowers in association with standard medication improved CINV, anxiety, sleep quality, appetite, overall mood, and quality of life. Our results add to the available evidence suggesting that medicinal cannabis flowers may offer valuable support in cancer palliative care integrated with standard-of-care oncology treatment. The successful individual funding request in this case demonstrates a pathway for other patients to gain access to these treatments, advocating for broader awareness and integration of cannabis-based medicinal products in national healthcare services.

Low dose of dexamethasone combined with netupitant and palonosetron in preventing nausea and vomiting in breast cancer patients induced by anthracycline drugs.

BACKGROUND: To study the effects of various courses of dexamethasone (DEX) combined with 5-HT3 receptor antagonists (RA) and NK-1 RA in suppressing high-grade nausea and vomiting (CINV) caused by anthracycline and cyclophosphamide chemotherapy regimens (AC or EC) in breast cancer (BC) patients. PATIENTS AND METHODS: A prospective study was performed with 252 BC patients who received AC between January, 2019 and June, 2022 in our hospital. Patients were randomly separated into control Group (N = 130) who received DEX 12 mg on day 1 and 8 mg per dose on day 2-4 and observation group (N = 122) treated with DEX 5 mg per dose on days 1-4. The response was monitored. Primary study endpoint was complete resolution (CR) of patients nausea or vomiting; secondary study endpoints included acute CR and delayed CR; and complete control (CC), acute CC, delayed CC, and safety. RESULTS: All patients underwent six rounds of chemotherapy, and no difference was found in the clinical data. CR of acute/delayed phase was (94.3%/88.5%, P > 0.05), (89.3%/90.8%, P > 0.05); total CR was (80.3%/81.5%, P > 0.05); CC was (56.6%/59.2%, P > 0.05), (64.8%/67.7%, P > 0.05); total CR was (48.4%/53.1%, P > 0.05). CONCLUSIONS: The preventive antiemetic effects of NEPA, a fixed-dose combination of netupitant and palonosetron combined with DEX 5 mg per dose on days 1-4, can be similar to DEX 12 mg on day 1 and 8 mg per dose on days 2-4, low-dose hormone with better safety, which is beneficial.

Health-Related Quality of Life And Economic Analysis of Olanzapine Versus Aprepitant in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy in Malaysia.

OBJECTIVES: Olanzapine has been shown to be effective in preventing chemotherapy-induced nausea and vomiting (CINV) after highly emetogenic chemotherapy (HEC); however, there is limited work on the impact of CINV on health-related quality of life (HRQoL) and the comparative cost-effectiveness of CINV prophylaxis in the Malaysian context. Therefore, this study was conducted to determine the HRQoL using EQ-5D-5L and the cost-effectiveness of olanzapine compared with aprepitant for CINV prophylaxis in Malaysia using data from a local study. METHODS: Fifty-nine chemo-naive patients receiving either olanzapine or aprepitant were randomly recruited and completed the EQ-5D-5L before and day 5 after HEC. HRQoL utility scores were analyzed according to the Malaysian valuation set. The economic evaluation was conducted from a healthcare payer perspective with a 5-day time horizon. Quality-adjusted life days (QALD) and the rate of successfully treated patients were used to measure health effects. The incremental cost-effectiveness ratio is assessed as the mean difference between groups' costs per mean difference in health effects. A one-way sensitivity analysis was performed to assess variations that might affect outcomes. RESULTS: Aprepitant and olanzapine arms' patients had comparable baseline mean HRQoL utility scores of 0.920 (SD = 0.097) and 0.930 (SD = 0.117), respectively; however, on day 5, a significant difference (P value = .006) was observed with mean score of 0.778 (SD = 0.168) for aprepitant and 0.889 (SD = 0.133) for olanzapine. The cost per successfully treated patient in the aprepitant arm was 60 times greater than in the olanzapine arm (Malaysian Ringgit [MYR] 927 vs MYR 14.83). Likewise, the cost per QALD gain in the aprepitant arm was 36 times higher than in the olanzapine arm (MYR 57.05 vs MYR 1.57). Incremental cost-effectiveness ratio of MYR -937.00 (USD -200.98) per successfully treated patient and MYR -391.84 (USD -85.43) per QALD gained for olanzapine compared with the aprepitant-based regimen. CONCLUSIONS: An olanzapine-based regimen is a cost-effective therapeutic substitution in patients receiving HEC in Malaysia.

Integrating nutrition, physical exercise, psychosocial support and antiemetic drugs into CINV management: The road to success.

Over the years, advancements in antiemetic drugs have improved chemotherapy-induced nausea and vomiting (CINV) control. However, despite the antiemetics therapies, in a relevant number of adult patients (∼30 %), CINV is still persistent, leading to several complications, such as electrolyte imbalances, anorexia, and treatment discontinuation. Supportive care interventions have gained credibility in cancer care, helping to improve patients' psycho-physical condition, quality of life, and managing symptoms, including CINV. Physical exercise and tailored nutritional counseling have demonstrated benefits in reducing the severity of nausea and vomiting. Psychological intervention has been postulated as a key approach in controlling anticipatory nausea/vomiting, as well as acupuncture/acupressure has been shown to decrease nausea and vomiting after chemotherapy treatments. In the current review, we aim to provide a clinical update on current prophylactic and delayed antiemetic guidelines for CINV and an overview of the non-pharmacological interventions tested for alleviating CINV in patients with cancer.

Two doses of fosaprepitant included prophylactic treatment for the three-day cisplatin-based chemotherapy induced nausea and vomiting.

PURPOSE: Neurokinin 1 receptor antagonists included prophylactic treatment was recommended for patients who receive one-day cisplatin chemotherapy. It is unclear whether the prolonged administration of fosaprepitant is effective for three-day cisplatin-based chemotherapy induced nausea and vomiting (CINV). We aim to explore the prophylactic antiemetic efficacy and safety of two doses of fosaprepitant included regimen in the patients receiving multiple-day cisplatin chemotherapy. METHODS: This randomized, parallel-group, open-labelled study was conducted in nine hospitals between February 2021 and February 2023. Patients diagnosed as lung cancer and chemotherapy naive were screened. Eligible participants were scheduled to be treated with highly emetogenic chemotherapy regimen which including three days of cisplatin. Then they were randomly divided into the experimental group (two doses of fosaprepitant, Group 2DF) and the control group (one dose of fosaprepitant, Group C). The primary endpoints included the safety and the average none CINV days (NCDs). This study was registered on the website of chictr.org.cn, number ChiCTR2100042665. RESULTS: Overall, 204 participants were randomly assigned, and 198 patients were analyzed. No statistical difference in adverse events was found between the two groups. All treatment-related adverse effects for fosaprepitant observed were of grade 1-2. The average NCDs of Group 2DF was significantly more than Group C (18.21 ± 3.40 days vs 16.14 ± 5.20 days, P = 0.001). Furthermore, the better life function score was achieved in Group 2DF according to FLIE questionnaire. CONCLUSION: The administration of two-dose fosaprepitant was safe and more effective than one dose in protecting patients from CINV induced by three-day cisplatin included chemotherapy.

2023 Japan Society of clinical oncology clinical practice guidelines update for antiemesis.

BACKGROUND: The Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis 2023 was extensively revised to reflect the latest advances in antineoplastic agents, antiemetics, and antineoplastic regimens. This update provides new evidence on the efficacy of antiemetic regimens. METHODS: Guided by the Minds Clinical Practice Guideline Development Manual of 2017, a rigorous approach was used to update the guidelines; a thorough literature search was conducted from January 1, 1990, to December 31, 2020. RESULTS: Comprehensive process resulted in the creation of 13 background questions (BQs), 12 clinical questions (CQs), and three future research questions (FQs). Moreover, the emetic risk classification was also updated. CONCLUSIONS: The primary goal of the present guidelines is to provide comprehensive information and facilitate informed decision-making, regarding antiemetic therapy, for both patients and healthcare providers.

A prospective randomized controlled clinical trial investigating the efficacy of low-dose olanzapine in preventing nausea and vomiting associated with oxaliplatin-based and irinotecan-based chemotherapy.

OBJECTIVE: The aim of this study is to assess the clinical efficacy of a 5 mg dosage of olanzapine in preventing chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC) among female patients diagnosed with gastrointestinal tract tumors. METHODS: Patients undergoing the oxaliplatin/irinotecan chemotherapy regimen were enrolled in this prospective controlled study. The olanzapine group received a 5 mg dosage of olanzapine along with palonosetron and dexamethasone, while the control group received a standard two-combination regimen consisting of dexamethasone and palonosetron. The primary endpoints included the total protection (TP) rates for the entire age group and the subgroup aged 60 years and above. Secondary endpoints encompassed the total protection rates during the acute and delayed phases within the two age brackets, as well as the total control (TC) rates and complete remission (CR) rates across all three phases (total, acute, and delayed). Additionally, the study involved the assessment of quality of life and the collection of adverse events associated with the interventions. RESULTS: 1) Regarding the primary endpoint, the total phase TP rates within both the entire age group and the age group exceeding 60 years demonstrated superiority in the olanzapine group when compared to the control group (66.7% vs 37.25%, P = 0.003; 68.8% vs 44.4%, P = 0.044). 2) In terms of secondary endpoints, the olanzapine group exhibited superior acute phase TP rates in both age brackets when compared to the control group (P < 0.05). The olanzapine group also demonstrated higher delayed-phase TP rates, TC rates across all three phases, and CR rates within the two age brackets, although the differences were not statistically significant (P > 0.05). Furthermore, the quality of life in the olanzapine group surpassed that of the control group for both age brackets (P < 0.05), characterized by enhanced appetite and a higher incidence of drowsiness in the patients treated with olanzapine when compared to those in the control group (P < 0.05). CONCLUSION: Olanzapine can enhance CINV induced by MEC regimen in female patients across all age groups, including the elderly, and therefore improve the quality of life for these patients. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/index.html , identifier: ChiCTR20000368269, 25/08/2020.

Bibliometric and visual analysis of chemotherapy-induced nausea and vomiting (2004-2023).

Background: Patients undergoing chemotherapy often encounter troubling and common side effects, notably Chemotherapy-induced nausea and vomiting (CINV). This side effect not only impairs the patient's quality of life but could also result in the interruption or discontinuation of the chemotherapy treatment. Consequently, research into CINV has consistently remained a focal point in the realm of clinical medicine. In this research domain, bibliometric analysis has not been conducted. The purpose of this study is to deliver a thorough summary of the knowledge framework and key areas of interest in the field of Chemotherapy-induced nausea and vomiting, using bibliometric methods. This approach aims to furnish novel concepts and pathways for investigators working in this area. Methods: Publications focusing on Chemotherapy-induced nausea and vomiting, spanning from 2004 to 2023, were identified using the Web of Science Core Collection (WoSCC) database. Tools such as VOSviewer, CiteSpace, and the R package "bibliometrix" were employed for this bibliometric analysis. Results: This research covers 734 publications from 61 countries, with the United States and China being the primary contributors. There has been a significant rise in the volume of papers published in the most recent decade compared to the one before it, spanning over the past twenty years. However, the annual publication rate in the last ten years has not shown a significant upward trend. The University of Toronto, Merck & Co., Sun Yat-sen University, and Helsinn Healthcare SA emerged as the principal research institutions in this field. Supportive Care in Cancer stands out as the most frequently published and cited journal in this domain. These works are contributed by 3,917 authors, with Rudolph M Navari, Matti Aapro, Shimokawa Mototsugu, and Lee Schwartzberg being among those who have published the most. Paul J. Hesketh is notably the most co-cited author. The primary focus of this research field lies in exploring the mechanisms of CINV and the therapeutic strategies for managing it. Key emerging research hotspots are represented by terms such as "Chemotherapy-induced nausea and vomiting," "nausea," "vomiting," "chemotherapy," and "antiemetics." Conclusion: This represents the inaugural bibliometric study to thoroughly outline the research trends and advancements in the field of CINV. It highlights the latest research frontiers and trending directions, offering valuable insights for scholars engaged in studying CINV.

Gene polymorphisms of TACR1 serve as the potential pharmacogenetic predictors of response to the neurokinin-1 receptor antagonist-based antiemetic regimens: a candidate-gene association study in breast cancer patients.

PURPOSE: The current candidate gene association study aims to investigate tag SNPs from the TACR1 gene as pharmacogenetic predictors of response to the antiemetic guidelines-recommended, NK-1 receptor antagonist-based, triple antiemetic regimens. METHODS: A set of eighteen tag SNPs of TACR1 were genotyped in breast cancer patients receiving anthracycline and cyclophosphamide (with/without docetaxel) applying real-time PCR-HRMA. Data analysis for 121 ultimately enrolled patients was initiated by defining haplotype blocks using PHASE v.2.1. The association of each tag SNP and haplotype alleles with failure to achieve the defined antiemetic regimen efficacy endpoints was tested using PLINK (v.1.9 and v.1.07, respectively) based on the logistic regression, adjusting for the previously known chemotherapy-induced nausea and vomiting (CINV) prognostic factors. All reported p-values were corrected using the permutation test (n = 100,000). RESULTS: Four variants of rs881, rs17010730, rs727156, and rs3755462, as well as haplotypes containing the mentioned variants, were significantly associated with failure to achieve at least one of the defined efficacy endpoints. Variant annotation via in-silico studies revealed that the non-seed sequence variant, rs881, is located in the miRNA (hsa-miR-613) binding site. The other three variants or a variant in complete linkage disequilibrium with them overlap a region of high H3K9ac-promoter-like signature or regions of high enhancer-like signature in the brain or gastrointestinal tissue. CONCLUSION: Playing an essential role in regulating TACR1 expression, gene polymorphisms of TACR1 serve as the potential pharmacogenetic predictors of response to the NK-1 receptor antagonist-based, triple antiemetic regimens. If clinically approved, modifying the NK-1 receptor antagonist dose leads to better management of CINV in risk-allele carriers.

Evaluation of chemotherapy-induced nausea and vomiting in pediatric patients with high-grade glioma treated with lomustine-a case series.

PURPOSE: Although lomustine has been used as a chemotherapeutic agent for decades, no recommendation on appropriate chemotherapy-induced nausea and vomiting (CINV) prophylaxis is available. As CINV is considered one of the most bothersome side effects of chemotherapy, adequate prophylaxis is of relevance to improve quality of life during cancer treatment. The aim of this retrospective case series was to report the incidence and severity of CINV in pediatric patients with high-grade glioma treated with lomustine and to formulate recommendations for appropriate CINV prophylaxis. METHODS: Pediatric patients treated with lomustine for high-grade glioma according to the ACNS 0423 protocol were identified retrospectively. Two researchers independently reviewed and classified complaints of CINV and administered CINV prophylaxis. Treatment details, tumor localization, and response to therapy were systematically extracted from the patients' files. RESULTS: Seventeen children aged 8-18 years received a median of four cycles of lomustine. CINV complaints and administered prophylaxis were evaluable in all patients. Moderate or severe CINV was observed in 13/17 (76%) patients. Administered prophylactic CINV regimens varied from no prophylaxis to triple-agent combinations. CONCLUSION: In this case series, we identified lomustine as a highly emetogenic chemotherapeutic agent. According to the current guidelines, CINV prophylaxis with a 5-HT3 receptor antagonist in combination with dexamethasone and (fos)aprepitant is recommended.

The clinical effect of an electric massage chair on chemotherapy-induced nausea and vomiting in cancer patients: randomized phase II cross-over trial.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse events in cancer patients and can negatively affect their quality of life (QoL). This study aimed to evaluate the clinical efficacy of an electric massage chair (EMC) for the treatment of CINV. METHODS: A randomized phase II cross-over trial was conducted on solid cancer patients who received moderate (MEC) to high emetogenic chemotherapy (HEC). The participants were randomly assigned to receive their first chemotherapy either on a standard bed (Group A) or in an EMC (Group B) during the infusion. The patients were then crossed over to the next cycle. CINV and QoL questionnaires were collected from the participants. RESULTS: A total of 59 patients completed the trial protocol and were included in the analysis, with 29 and 30 patients in Groups A and B, respectively. The mean INVR (Index of Nausea, Vomiting, and Retching) score in the 2nd day of the first cycle was higher in Group B (3.63 ± 5.35) than Group A (2.76 ± 4.78), but the difference was not statistically significant (p = 0.5367). The complete response rate showed little difference between the groups. Among the high-emetic risk subgroups, patients who received HEC (p = 0.04595), younger patients (p = 0.0108), and non-colorectal cancer patients (p = 0.0495) presented significantly lower CINV scores when EMC was applied. CONCLUSION: Overall, there was no significant difference in INVR scores between standard care and EMC. Applying EMC at the first chemotherapy infusion may help preserve QoL and reduce CINV in high-risk patients. TRIAL REGISTRATION: KCT0008200, 17/02/2023, Retrospectively registered.

Comparison of oral aprepitant and intravenous fosaprepitant for prevention of chemotherapy-induced nausea and vomiting in pediatric oncology patients: a randomized phase III trial.

Background: Neurokinin-1 receptor antagonists have improved the management of chemotherapy-induced nausea and vomiting (CINV), but to date there has been no prospective comparison between oral aprepitant and intravenous fosaprepitant in pediatric oncology patients. Methods: Our study was a double-parallel study, and the distribution ratio was 1:1. Children aged 2-12 years who were undergoing moderate or highly emetogenic chemotherapy (MEC or HEC) were randomly assigned to receive ondansetron and dexamethasone combined with either a single dose of intravenous fosaprepitant (arm A), or 3 days of oral aprepitant (arm B). The primary outcome measure was the rate of complete response (CR) of CINV within the acute phase, defined as from the start through 24 hours after the last chemotherapy dose. Response during the delayed phase, overall response, and use of rescue antiemetics were also assessed. Results: We prospectively evaluated 108 eligible patients, including 55 receiving fosaprepitant. Study observations were made during a single cycle for each patient. The occurrence of CR in the acute phase was statistically higher for patients receiving fosaprepitant (95% vs. 79%, P=0.018<0.05). Modest differences were seen in CR rates during the delayed phase (71% vs. 66%, P=0.586), and overall response rate (69% vs. 57%, P=0.179). The use of antiemetic rescue medicines was similar between arms A (11%) and B (7%). Conclusions: Fosaprepitant produced more CRs of CINV in the acute phase than did aprepitant, although there were no statistical differences in delayed phase response, overall response, or use of rescue antiemetics. This study confirms the safety, efficacy, and potential advantages of fosaprepitant in reducing CINV in pediatric oncology patients. Trial Registration: ClinicalTrials.gov identifier: NCT04873284.

Adherence to antiemetic guidelines in solid cancer patients receiving highly emetogenic chemotherapy in Korea.

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.

Safety and tolerability of intravenous aprepitant and fosaprepitant in children with cancer: A retrospective, single-center review.

NK-1 receptor antagonists (NK1-RA) are key agents for chemotherapy-induced nausea and vomiting (CINV) prevention in patients receiving highly emetogenic chemotherapy. Current pediatric practice guidelines recommend the use of intravenous fosaprepitant or oral aprepitant. However, there are reports of hypersensitivity reactions with fosaprepitant due to polysorbate 80. Intravenous aprepitant does not contain polysorbate 80, but its use in pediatric patients has not been described. In this retrospective, single-center study, 106 pediatric patients received either fosaprepitant or intravenous aprepitant as part of their antiemetic regimen. Intravenous aprepitant was well tolerated and did not lead to any instances of hypersensitivity reactions requiring discontinuation.

Effect of a Standardized Ginger Root Powder Regimen on Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Double-Blind, Placebo-Controlled Randomized Trial.

BACKGROUND: There is substantial interest in the role of ginger as an adjuvant therapy for chemotherapy-induced nausea and vomiting (CINV). However, available evidence lacks robust methodology. OBJECTIVE: To assess the effect of adjuvant ginger compared with placebo on chemotherapy-induced nausea-related quality of life (QoL) and CINV-related outcomes. DESIGN: A parallel, double-blind, placebo-controlled randomized trial with 1:1 allocation was conducted. PARTICIPANTS/SETTING: One hundred three chemotherapy-naïve adults scheduled to receive moderately to highly emetogenic chemotherapy at two hospitals in Australia were enrolled and analyzed. INTERVENTION: Four standardized ginger capsules (totaling 84 mg/day active gingerols/shogaols), or placebo, were administered commencing the day of chemotherapy and continuing for 5 days for chemotherapy cycles 1 through 3. MAIN OUTCOME MEASURES: The primary outcome was chemotherapy-induced nausea-related QoL. Secondary outcomes were vomiting- and CINV-related QoL; anticipatory, acute, and delayed nausea and vomiting; fatigue; nutritional status; depression and anxiety; health-related QoL; and adverse events. STATISTICAL ANALYSES PERFORMED: Intention-to-treat analysis was performed. Mixed analysis of variance with repeated measures determined differences between groups. The null hypothesis was no difference between groups. After applying a Bonferroni multiple testing correction, evidence against the null hypothesis was considered at P= 0.003. RESULTS: One hundred three participants (ginger: n = 52; placebo: n = 51) were enrolled and analyzed. There was clinically relevant evidence against the null hypothesis, favoring ginger, in change scores for nausea-related QoL (F[df] = 9.34[1,101]; P = 0.003; partial η2 = 0.09), overall CINV-related QoL (F[df] = 12.26[1,101]; P < 0.001; partial η2 = 0.11), delayed nausea severity (F[df] = 9.46[1,101]; P = 0.003; partial η2 = 0.09), and fatigue (F[df] = 10.11[1,101]; P = 0.002; partial η2 = 0.09). There was a clinically meaningful lower incidence of delayed nausea and vomiting in the ginger group at Cycle 2 (53% vs 75%; P = 0.020 and 4% vs 27%; P = 0.001, respectively) and Cycle 3 (49% vs 79%; P = 0.002 and 2% vs 23%; P = 0.001, respectively). There was a clinically meaningful lower incidence of malnutrition in the ginger group at Cycle 3 (18% vs. 41%; P = 0.032) and in change scores for Patient-Generated Subjective Global Assessment (F[df)] = 4.32[1,100]; P = 0.040; partial η2 = 0.04). Change scores between groups favored ginger for vomiting-related QoL and number of vomiting episodes; however, findings were not clinically meaningful. There was no effect of ginger on anticipatory or acute CINV, health-related QoL, anxiety, or depression. No serious adverse events were reported. CONCLUSIONS: Ginger supplementation was a safe adjuvant to antiemetic medications for CINV that enhanced QoL during chemotherapy treatment. Future trials are needed to examine dose-dependent responses to verify optimal dosing regimens.

A multicenter phase II trial of the triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine for a cisplatin-containing regimen. - PATROL-I.

Dexamethasone is one of the key antiemetic agents and is widely used even now. However, dexamethasone has been associated with several adverse reactions even after short-term administration. Therefore, developing a steroid-free antiemetic regimen is an important issue to consider. Thus, the purpose of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine in a multi-institutional phase II study. Chemotherapy-naive patients scheduled to receive cisplatin were enrolled and evaluated for the occurrence of chemotherapy-induced nausea and vomiting during 120 h after chemotherapy. The primary endpoint of the study was total control (TC) in the overall phase. The key secondary endpoint was complete response (CR), which was assessed in the acute, delayed, and overall phase, respectively. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events. Eighty-five patients were enrolled from 8 centers in Japan, of which 83 were evaluable for analyses. The percentage of patients who achieved TC during the overall phase was 31.3%. CR was achieved in 61.4%, 84.3%, and 65.1% of patients during the overall, acute, and delayed phases, respectively. The most frequently reported adverse event was anorexia. The primary endpoint was below the threshold and we could not find benefit in the dexamethasone-free regimen, but CR during the overall phase was similar to that of the conventional three-drug regimen. This antiemetic regimen without dexamethasone might be an option for patients for whom corticosteroids should not be an active application.