Antiemetic Combination Research Articles

Management of nausea and vomiting (N/V) following first-line (1L) zolbetuximab + chemotherapy treatment in claudin-18.2 (CLDN18.2)+, HER2−, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Analysis from the phase 3 SPOTLIGHT and GLOW studies.

372 Background: The phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) studies showed clinically meaningful, statistically significant improvement in PFS and OS using 1L zolbetuximab + chemotherapy vs placebo (PBO) + chemotherapy in patients (pts) with CLDN18.2+, HER2−, LA unresectable or mG/GEJ adenocarcinoma. N/V were the most common treatment-emergent adverse events (TEAEs) reported in the zolbetuximab arm of these studies. We report an analysis of the incidence and management of N/V in SPOTLIGHT and GLOW. Methods: In SPOTLIGHT, pts (N = 565) were randomized 1:1 to zolbetuximab + mFOLFOX6 vs PBO + mFOLFOX6. In GLOW, pts (N = 507) were randomized 1:1 to zolbetuximab + CAPOX vs PBO + CAPOX. In both studies, neurokinin-1 receptor blockers (NK-1), selective serotonin receptor blockers (5-HT3), and other prophylactic antiemetic regimens were recommended to prevent and mitigate N/V per institutional care and guidelines. Results: A total of 279 pts in SPOTLIGHT and 253 pts in GLOW received zolbetuximab + chemotherapy. In SPOTLIGHT and GLOW combined, nausea occurred in 58% vs 18% of pts, and vomiting occurred in 43% vs 15% of pts in the first vs second zolbetuximab infusions, respectively; lower incidences of N/V were observed thereafter. During the first zolbetuximab infusion, the first episode of N/V occurred within 1 hour (median time, 48.0 min in SPOTLIGHT and 56.5 min in GLOW). Antiemetic usage and associated N/V rates are presented in the Table. The 96 pts in SPOTLIGHT and 52 pts in GLOW who had infusion modifications in cycle 1 due to TEAEs had numerically higher infusion rates than pts without infusion modifications; 85% of these modifications in SPOTLIGHT and 79% in GLOW were due to N/V. Zolbetuximab was discontinued within the first 9 weeks in 11 and 7 pts in SPOTLIGHT and 6 and 4 pts in GLOW due to nausea or vomiting, respectively. Conclusions: In SPOTLIGHT and GLOW, slower infusion rate and use of antiemetic combinations may have helped to mitigate N/V. These strategies will be important to support continued treatment and allow pts to achieve maximum clinical benefit with zolbetuximab + chemotherapy. Clinical trial information: NCT03504397 and NCT03653507 . [Table: see text]

Laporan Kasus : Feline Immunodeficiency Virus pada Kucing Moi di Surabaya

Feline immunodeficiency (FIV) is a disease caused by retroviridae of the lentivirus genus and is dangerous for cats. This virus attacks the cat's immune system. FIV disease can be transmitted horizontally via as saliva and body fluids. 5-month-old black and white Persian cat named Moi, brought by the owner with complaints of vomiting yesterday, refusing to eat and drink, soft stool, no coughing and sneezing, weakness. On physical examination showed a temperature of 40.1 °C with a body weight of 1.5 kg, clinical symptoms were found in the form of gingivitis, canker sores, conjunctivitis, pale pink mucous membranes, fever, flu symptoms from the nose with clear discharge, crepitus in both ears. Diagnosis of Moi Cats based on anamnesis, physical examination, clinical symptoms, and supporting examinations is diagnosed with Feline immunodeficiency virus (FIV). Case are treated using a combination of antibiotics, anti-inflammatories, fluid therapy, antiemetics, gastrointestinal linings, immune boosters, blood boosters, and cardiac pacemakers. After 4 days the cat Moi was declared dead due to failure of platelet hemostasis, bleeding, and heart failure.

Influence of menopause on chemotherapy-induced nausea and vomiting in highly emetogenic chemotherapy for breast cancer: A retrospective observational study.

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

Evaluation and Comparison of Two Different Combined Regimens for Prophylaxis of Nausea and Vomiting After Laparoscopic Bariatric Surgery: A Double-Blinded Randomized Clinical Trial

Postoperative Nausea and vomiting (PONV) are the most complications after laparoscopic surgeries, especially laparoscopic bariatric surgeries. The incidence of PONV has been estimated in over two-thirds of patients undergoing laparoscopic bariatric surgeries. Prophylactic combined antiemetic therapy is recommended for patients undergoing these surgeries. This is a double-blinded randomized clinical trial. Eighty-three patients of ASA physical status I and II undergoing elective bariatric laparoscopic surgery were enrolled in this clinical trial and divided into two equal groups through simple randomization using a random number table. One group (group A) received a combination of ondansetron, dexamethasone, and haloperidol (ODH); and the other group (group B) received a combination of ondansetron, dexamethasone, and promethazine (ODP). The ODP group received promethazine 25 mg IM 30 minutes before extubation and ODH group received haloperidol 2 mg IM at the beginning of the surgery. Nausea and vomiting were assessed in terms of severity and frequency in the recovery room, 6, and 24 hours postoperatively in both groups using the Numeric Verbal Rating Scale (NVRS). The frequency of PONV was significantly lower in the ODH group compared to the ODP group in the recovery room (20% versus 40%). PONV severity was lower in the ODH group compared to the ODP group. The time to first rescue antiemetic prescription in the ODP group was more than in the ODH group (7.2 h versus 2.6 h). In morbidly obese patients undergoing laparoscopic bariatric surgery, both antiemetic combinations decreased the incidence of PONV, but the combination of haloperidol, dexamethasone, and ondansetron was more effective than promethazine, dexamethasone, and ondansetron.

A pharmacological overview of aprepitant for the prevention of postoperative nausea and vomiting

ABSTRACT Introduction Post-operative nausea and vomiting (PONV) affects 30% of all patients undergoing surgery and up to 80% of high-risk patients. Antiemetics for PONV prophylaxis target a variety of receptor systems, with varying degrees of efficacy and side effect profile. Neurokinin −1 receptor antagonists are the most recent class of compounds investigated for PONV prophylaxis, with aprepitant being the only one currently approved for this indication. Areas covered This review covers the pathophysiology of PONV, current recommendations for PONV prophylaxis, pharmacokinetics, and pharmacodynamics of aprepitant, and the evidence for its efficacy in the management of PONV as a single agent and in combination therapy. Expert opinion Aprepitant is effective for PONV prophylaxis. It has superior antivomiting efficacy, long half-life, and favorable side effect profile. Data on antiemetic combinations involving aprepitant are limited, and it is not clear if the addition of other antiemetics to aprepitant results in improved PONV prophylaxis. The oral route of administration of aprepitant is a potential limitation in a busy clinical practice. However, the recent approval of an intravenous formulation could provide a more convenient route of administration. Aprepitant remains more expensive than other antiemetics, and there are no studies assessing the cost effectiveness of its use.

Risk factors for postoperative nausea and vomiting in patients of orthognathic surgery according to the initial onset time: a cross-sectional study.

A high incidence (40-73%) of postoperative nausea and vomiting (PONV) has been reported following orthognathic surgery, and various risk factors have been associated with it. Identifying PONV risk factors based on initial onset time will help establish preventive measures. This study aimed to identify factors that are significantly related to PONV based on the initial onset time after orthognathic surgery. This study included 590 patients who underwent orthognathic surgery. Multivariate logistic regression analysis was performed to identify the risk factors that are significantly related to PONV. The objective variables were classified into three categories: no PONV, early PONV (initial onset time: 0-2 h after anesthesia), and late PONV (initial onset time: 2-24 h after anesthesia). The explanatory variables included relevant risk factors for PONV, as considered in previous studies. Total intravenous anesthesia with propofol was a significant depressant factor for early PONV (adjusted odds ratio [aOR] = 0.340, 95% confidence interval [CI] = 0.209-0.555) and late PONV (aOR = 0.535, 95% CI = 0.352-0.814). The administration of a combination of intraoperative antiemetics (vs. no administration) significantly reduced the risk of early PONV (aOR = 0.464, 95% CI = 0.230-0.961). Female sex and young age were significant risk factors for late PONV (aOR = 1.492, 95% CI = 1.170-1.925 and unit aOR = 1.033, 95% CI = 1.010-1.057, respectively). We identified factors that are significantly related to PONV based on the initial onset time after orthognathic surgery. Total intravenous anesthesia with propofol significantly reduced the risk of PONV not only in the early period (0-2 h after anesthesia) but also in the late period (2-24 h after anesthesia).

Netupitant-palonosetron (NEPA) for Preventing Chemotherapy-induced Nausea and Vomiting: From Clinical Trials to Daily Practice.

Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event associated with many anticancer therapies and can negatively impact patients' quality of life and potentially limit the effectiveness of chemotherapy. Currently, CINV can be prevented in most patients with guideline-recommended antiemetic regimens. However, clinicians do not always follow guidelines, and patients often face difficulties adhering to their prescribed treatments. Therefore, approaches to increase guideline adherence need to be implemented. NEPA is the first and only fixed combination antiemetic, composed of netupitant (oral)/fosnetupitant (intravenous) and palonosetron, which, together with dexamethasone, constitute a triple antiemetic combination recommended for the prevention of CINV for patients receiving highly emetogenic chemotherapy and for certain patients receiving moderately emetogenic chemotherapy. Thus, NEPA offers a convenient and straightforward antiemetic treatment that could improve adherence to guidelines. This review provides an overview of CINV, evaluates the accumulated evidence of NEPA's antiemetic activity and safety from clinical trials and real-world practice, and examines the preliminary evidence of antiemetic control with NEPA in daily clinical settings beyond those described in pivotal trials. Moreover, we review the utility of NEPA in controlling nausea and preserving patients' quality of life during chemotherapy, two major concerns in managing patients with cancer.

Combination Antiemetic Therapy for Chemotherapy-Induced Nausea and Vomiting in Patients with NSCLC Receiving Carboplatin-Based Chemotherapy.

PurposeThe incidence of delayed chemotherapy-induced nausea and vomiting (CINV) in patients with non-small cell lung cancer (NSCLC) receiving carboplatin (CBDCA)-based chemotherapy (CBDCA + pemetrexed or paclitaxel) has not been clearly described. Therefore, we attempted to evaluate whether delayed CINV could be controlled using a combination of three antiemetics and identify individual risk factors.MethodsWe pooled data from two prospective observational studies, namely a nationwide survey of CINV and a prospective, observational study in Japan, to assess whether delayed CINV could be controlled using a combination of three antiemetics and identified individual risk factors via inverse probability treatment-weighted analysis.ResultsIn total, 240 patients were evaluable in this study (median age, 66 years; male, 173; female, 67). The three-antiemetic regimen controlled delayed nausea (31.6% vs 47.3%) and vomiting (5.1% vs 23.1%) better than two antiemetics. Younger age (<70 years; odds ratio [OR] = 2.233), motion sickness (OR = 3.472), drinking habits (OR = 1.972), receipt of the CBDCA + pemetrexed regimen (OR = 2.041), and the use of two antiemetics (OR = 1.926) were risk factors for delayed nausea. Female sex (OR = 3.372), drinking habits (OR = 2.272), receipt of the CBDCA+ pemetrexed regimen (OR = 2.314), and the use of two antiemetics (OR = 6.830) were risk factors for delayed vomiting.ConclusionFemale sex, younger age, and receipt of the CBDCA + pemetrexed regimen increased the risk of CINV. Therefore, we recommend additional supportive antiemetics treatment for these patients.

Clinical interaction between dexamethasone and aprepitant in chemotherapy for lymphoma.

Aprepitant (Apr) is an effective antiemetic agent for chemotherapy-induced nausea and vomiting (CINV). Current CINV guidelines recommend the antiemetic combination of a 5-HT3 receptor antagonist, Apr, and dexamethasone (Dex) for highly emetogenic chemotherapies. Apr inhibits CYP3A4 dose-dependently. Since Dex is metabolized by CYP3A4, the combined use of Apr and Dex inhibits Dex metabolism. CINV guidelines therefore recommend dose-reduction of Dex when Apr and Dex are used together. However, there is some controversy over whether or not Dex should be reduced when administered as an antitumor agent for lymphoid malignancies. We retrospectively compared the antitumor effect of Dex-containing chemotherapy in which Dex is administered at the usual dose without Apr (group A) or administered at a half-dose in combination with Apr (group B). We analyzed 62 consecutive patients with refractory or relapsed CD20 + B cell lymphoma who received R-DHAP therapy in our hospital, including 29 and 33 cases in groups A and B, respectively. The response rate at the end of the first course of R-DHAP was 62.1% and 54.5%, respectively (P = 0.61). As another endpoint to evaluate the effect of Dex, group B tended to show greater suppression of the lymphocyte count (P = 0.05). Therefore, decreasing the dose of Dex by half appeared to be reasonable when combined with Apr.

The effect of intraoperative antiemetics on postoperative nausea and vomiting in patients receiving intrathecal morphine for elective caesarean deliveries

Background: The incidence of postoperative nausea and vomiting (PONV) when intrathecal morphine (ITM) is used for caesarean delivery (CD) is up to 80% without antiemetic prophylaxis. Prophylactic antiemetics can reduce this rate by 50%, except for dexamethasone that did not show to be effective in this context. Combinations showed divergent results. We investigated the incidence of PONV when different combinations of antiemetics were used for CD in parturients receiving ITM. Methods: Retrospective, single centre cohort study of patients undergoing elective CD with ITM between January 2016 and October 2017. The primary outcome was the incidence of PONV requiring treatment in the first 24 hours following CD. Interactions were sought using multivariate modelling for predictors of PONV following surgery. Results: Overall, 598 women were included in the study. The rate of PONV requiring treatment was 29.1%. The rate of PONV decreased with increasing numbers of prophylactic medications (p &lt; 0.001). Women who did not experience PONV received a greater number of antiemetics in the operating room (p &lt; 0.001). There was a dose response relationship between ITM dose and PONV rate (p &lt; 0.001). Dexamethasone, either alone or in combination with other agents was not protective against PONV when compared with other drug combinations (p = 0.08). Conclusions: We have demonstrated an inverse relationship between the number of prophylactic antiemetics given and the rates of PONV after caesarean delivery in the context of intrathecal morphine use. Dexamethasone use, either alone or in conjunction with other drugs did not offer advantages over other combinations where dexamethasone was avoided.

Addition of metoclopramide to triple antiemetic therapy towards prevention of anthracycline-based chemotherapy-induced nausea and vomiting in breast cancer patients

Objective: The aim of this study was to evaluate if addition of metoclopramide to the triplet antiemetic therapy is superior to the triplet antiemetic therapy for prevention of delayed chemotherapy-induced nausea and vomiting. Materials and Methods: A randomized single-blind trial was performed on 200 chemotherapy-naïve breast cancer patients who have to receive anthracycline-based highly emetogenic chemotherapy (HEC). The patients were randomized to study arm (n = 100) and control arm (n = 100). Triplet antiemetic therapy (fosaprepitant on day 1, 5-HT3 antagonist on day 1, and dexamethasone for days 1–4) was used in both the arms and metoclopramide (day 1–5) was added to the study arm. Response to antiemetic prophylaxis was assessed in terms of “complete response (CR),” “only nausea,” and “both nausea and vomiting.” CR is defined as no nausea, no vomiting, and no rescue medication during the overall phase (days 1–5). Nausea/vomiting was detected by using the Visual Analog Scale and its impact on quality of life was determined by using the Functional Living Index Emesis (FLIE) score. Results: The demographical and clinical features were similar in both the groups. Majority of patients in both the arms presented with Eastern Cooperative Oncology Group PS 0, Stage III, and positive hormone receptor status. CR was observed more in the study arm than that of the control arm (51% vs. 37%; P = 0.046). The mean total FLIE score was 29.23 in the study arm and 31.16 in the control arm (P = 0.036). Conclusion: This study resulted in a significant CR and clinically relevant improvement in FLIE score for addition of metoclopramide to triple antiemetic prophylaxis. Therefore, a quadruple antiemetic combination including metoclopramide might be an antiemetic prophylaxis option for breast cancer patients receiving anthracycline-based HEC for better compliance to treatment.

Effect of Anti-Emetic Combination of Sevoflurane / Propofol Anesthesia Technique in Laparoscopic Cholecystectomy

Objective: To assess symptoms of nausea and vomiting in laparoscopic cholecystectomy post-operatively, administered anesthesia by sevoflurane or propofol and to assess the effect of dexamethasone and ondansetron anti-emetic combination. Study design &amp; Setting: It was an experimental study design conducted from 08-Oct-2017 till 11-Jul-2018 at Rawal General &amp; Dental Hospital. Methodology: Patients were recruited in interventional groups by lottery method as n=160, with 80 cases allocated in each group. The patients with gallstones planned for laparoscopic cholecystectomy after preoperative assessment were classified to American Society of Anesthesiologist (ASA) physical status class I-II. All the patients placed in a particular ASA physical status class were (exposed to both induction methods) either anesthetic induction by propofol 1-2 mg/kg (group-A) or by employing sevoflurane 4-8% (group-B) in combination with oxygen, while maintenance was done in both study groups with 2% sevoflurane and 50% nitrous oxide in oxygen. After procedure patients stayed in post-anesthesia care unit where intra-operative monitoring was evaluated. The primary end point of the study was to note the rate of nausea and vomiting in 24 hours interval after surgery. Results: Both sevoflurane and propofol are equally effective anesthetic induction agents. The same combination of dexamethasone and ondansetron was given to both groups and so the actual effect of both anesthesia drugs in terms of side effects were nullified. Conclusion: In laparoscopic cholecystectomy, both sevoflurane and propofol are good enough when administered with dexamethasone and ondansetron anti-emetic combination, for post-operative nausea and vomiting up to 24 hours observation time in study.

Cost-effectiveness analysis of antiemetics therapy in breast cancer patients with moderate emetogenic chemotherapy in Prof. Dr. Margono Soekarjo Hospital, Indonesia

Chemotherapy-induced nausea and vomiting (CINV) significantly reduce the life quality of cancer patients. A 5-HT3 receptor antagonist, corticosteroid, and H2-blocker have been used to control moderate nausea and vomit in cancer patients. The exploration of the cost-effectiveness of several antiemetic combinations in breast cancer patients in Prof. Dr. Margono Soekardjo Hospital, Purwokerto, Indonesia was the aim of this research. Seventy-four Breast cancer patients who have prescribed moderate-emetogenic chemotherapy during the year 2017-1019 were included in this research. There were fifteen patients treated with the combination of ondansetron and dexamethasone (OD). Fourteen patients were treated with the combination of ondansetron and ranitidine (OR). Thirty-five patients were treated using ondansetron, dexamethasone, and ranitidine (ODR) combination. The effectiveness was represented by the absence of acute nausea and vomiting after receiving chemotherapy. The ODR combinations showed the highest effectivity on diminishing nausea and vomiting among breast cancer patients (0.400), followed by the OD combination (0.267) and the OR combination (0.214). However, the ODR combination generates the highest cost (4.6 million rupiahs) compared to other antiemetics combinations. Compared to the combination of ondansetron and dexamethasone, the combination of ODR provides higher ICER (ICER of 13 Million Rupiahs per case prevented) than the combination of OR (ICER of 8.5 million Rupiahs per case prevented). In conclusion, the combination of ondansetron, dexamethasone, and ranitidine generates the highest cost. It also provides the highest effectiveness in preventing nausea and vomiting.

Update PONV – Was gibt es Neues bei der Prophylaxe und Therapie von postoperativer Übelkeit und postoperativem Erbrechen?

The prophylaxis and treatment of postoperative pain to enhance patient comfort has been aprimary goal of anesthesiologists for the last decades; however, avoiding postoperative nausea and vomiting (PONV) is, from apatient's perspective, ahighly relevant and equally important goal of anesthesia. Recent consensus-based guidelines suggest the assessment of risk factors including female gender, postoperative opioid administration, non-smoking status, ahistory of PONV or motion sickness, young patient age, longer duration of anesthesia, volatile anesthetics and the type of surgery and reducing the patient's baseline risk (e.g. through the use of regional anesthesia and administration of non-opioid analgesics as part of amultimodal approach). In general, aliberal PONV prophylaxis is encouraged for adult patients and children, which should also be administered when no risk assessment is made. The basis for every adult patient should be astandard prophylaxis with two antiemetics, such as dexamethasone in combination with a5-HT3 receptor antagonist. In patients at high risk, this should be supplemented by athird and potentially a fourth antiemetic prophylaxis with adifferent mechanism of action. Arecently published comprehensive Cochrane meta-analysis comparing available antiemetic prophylaxes reported the highest effectiveness to prevent PONV for the NK1 receptor antagonist aprepitant (relative risk, RR 0.26), followed by ramosetron (RR 0.44), granisetron (RR 0.45), dexamethasone (RR 0.51) and ondansetron (RR 0.55), thereby revising the dogma that every antiemetic is equally effective. Adverse events of antiemetics were generally rare and reported in less than half of the included studies, yielding alow quality of evidence for these end points. In general, combinations of different antiemetics were more effective than single prophylaxes. In children above 3years of age, the same principles should be applied as in adults. For these patients, there is ahigh degree of evidence for the combination of dexamethasone and 5‑HT3 receptor antagonists. When PONV occurs, the consensus guidelines suggest that antiemetics from aclass different than given as prophylaxis should be administered. To decrease the incidence of PONV and increase the quality of care, the importance of the implementation of institutional-level guidelines and protocols as well as assessment of PONV prophylaxis and PONV incidence is highly recommended.

LBA64 Olanzapine, an alternative to dexamethasone for preventing nausea and vomiting induced by cisplatin-based doublet highly emetogenic chemotherapy: A non-inferiority, prospective, multi-centered, randomized, controlled, phase III clinical trial

LBA64 Olanzapine, an alternative to dexamethasone for preventing nausea and vomiting induced by cisplatin-based doublet highly emetogenic chemotherapy: A non-inferiority, prospective, multi-centered, randomized, controlled, phase III clinical trial

Single-Agent Oral Vinorelbine in the Treatment of Pediatric Progressive Optic Pathway Glioma: A Single Institutional Experience

Purpose: The vinca alkaloids’ activity against pediatric low-grade glioma (PLGG) is well established. The goal of the present study is to describe our experience with oral vinorelbine in patients with progressive optic pathway glioma (OPG), not only regarding the clinical response, but also the cost benefit using an oral medication. Methods: Patients under 21 years of age with unresectable and/or progressive OPG were eligible. Oral vinorelbine was administered at a dose of 90mg/m2 daily on days 0, 8 and 22, in a scheme of 4 weekly cycles for a total of 18 cycles (54 doses). Results: From 2013 to 2018, sixteen patients were enrolled onto the study, with a median age of 9,1 years (range 4,6-17,8y). The most common histology was pilocytic astrocytoma (88,8%). Best response to chemotherapy was reviewed with a response rate (complete, partial, or minor response) of 30% for the patients treated exclusively with the oral drug. Five-year event-free survival (EFS) rate was 43.4%. Six patients had to change to intravenous vinorelbine due to gastrointestinal toxicity, vomiting grade III. None of the patients showed neurotoxicity. The total cost including drug acquisition, administration and toxicity management was lower with the oral formulation comparing to IV one. Conclusion: Single-agent oral vinorelbine seems to have some clinical activity in the management of recurrent or refractory pediatric OPG, being an interesting and cost-effective option, minding that gastrointestinal toxicity may be limiting and a combination of antiemetics should be considered in this treatment regimen.

Palonosetron for Patients Undergoing High or Moderate Emetogenic Chemotherapy

&#x0D; This report identified high to moderate quality evidence from clinical studies and economic evaluations, as well as high-quality guidelines regarding the use of palonosetron in the prevention of chemotherapy-induced nausea and vomiting in adult and pediatric patients receiving different emetogenic chemotherapies. Interpretations of the findings should be taken with caution because of the presence of some identified limitations in both clinical and economic evidence.&#x0D; In adult patients receiving high emetogenic chemotherapy, a fixed antiemetic combination of netupitant and palonosetron (NEPA) plus dexamethasone demonstrated noninferiority relative to a triple regimen of granisetron-aprepitant-dexamethasone. Similarly, palonosetron had similar efficacy compared to granisetron with the co-administration of neurokinin 1 receptor antagonist (e.g., aprepitant or fosaprepitant) and dexamethasone. However, in the absence of aprepitant, a 2-drug combination of palonosetron-dexamethasone appeared to be significantly more effective than granisetron-dexamethasone for the prevention of both acute and delayed emesis.&#x0D; In adult patients receiving moderate emetogenic chemotherapy, palonosetron plus dexamethasone was found to be noninferior compared with ondansetron plus dexamethasone. Similar efficacy was also observed between palonosetron plus dexamethasone and transdermal granisetron plus dexamethasone.&#x0D; In a mixed population of adult patients receiving high or moderate emetogenic chemotherapy, a palonosetron regimen appeared to have greater efficacy than ondansetron for delayed emesis. The efficacy of triple regimen of palonosetron-aprepitant-dexamethasone and granisetron-aprepitant-dexamethasone was comparable at all phases.&#x0D; In pediatric patients receiving high emetogenic chemotherapy, palonosetron plus dexamethasone had similar efficacy compared with ondansetron plus dexamethasone in the acute phase, but was more effective in delayed and overall phases of chemotherapy-induced nausea and vomiting.&#x0D; In a mixed population of pediatric patients receiving high or moderate emetogenic chemotherapy, palonosetron plus dexamethasone was noninferior to ondansetron plus dexamethasone.&#x0D; There were no significant differences between palonosetron and ondansetron or between palonosetron and granisetron treatment regimens in adverse events or quality of life.&#x0D; A cost-utility analysis revealed that NEPA plus dexamethasone was dominant (i.e., cost less, more effective) relative to granisetron-aprepitant-dexamethasone and ondansetron-aprepitant or fosaprepitant-dexamethasone in adult patients receiving high emetogenic chemotherapy. In contrast, double or triple regimens of palonosetron was not cost-effective compared to granisetron regimens, mainly due to large difference in price and small quality-adjusted life-years gained. These economic evaluations may not be applicable to the Canadian context.&#x0D; The identified high-quality guidelines have recommendations on the use of specific antiemetic regimens for adult and pediatric patients receiving high emetogenic chemotherapy or moderate emetogenic chemotherapy and suggest that palonosetron may be offered as an alternative to other 5-hydroxytryptamine-3 receptor antagonists and that 1 5-hydroxytryptamine-3 receptor antagonist is not preferred over another based on the available evidence.&#x0D;

Efficacy of intravenous NEPA, a fixed NK1/5-HT3 receptor antagonist combination, for the prevention of chemotherapy-induced nausea and vomiting (CINV) during cisplatin- and anthracycline cyclophosphamide (AC)-based chemotherapy: A review of phase 3 studies.

This paper presents an overview of the efficacy of intravenous (IV) NEPA (fixed combination of the NK1RA, fosnetupitant, and 5-HT3RA, palonosetron) relative to oral NEPA and also to historical data for other NK1RA regimens. Data is compiled from 5 pivotal NEPA studies in adult chemotherapy-naïve patients with solid tumors undergoing either cisplatin- or anthracycline cyclophosphamide (AC)-based chemotherapy. Additionally, data was reviewed from 10 pivotal Phase 3 studies utilizing other NK1RA regimens approved for clinical use. The overall (0-120 h) complete response (no emesis, no rescue use), no emesis, and no significant nausea rates for IV NEPA were similar to that of oral NEPA and were consistently numerically higher than historical NK1RA regimens. As a single-dose prophylactic antiemetic combination given with dexamethasone, IV NEPA is a highly effective and convenient guideline-compliant antiemetic agent which may offer a safety benefit over other IV NK1RA regimens due to its lack of associated hypersensitivity and injection-site reactions.

Antiemetic Prophylaxis with NEPA (NETUPITANT/PALONOSETRON) and Dexamethasone to Prevent Chemotherapy-Induced Nausea and Vomiting (CINV) in Hodgkin’S Lymphoma Naïve Patients Receiving ABVD Regimen: A Multicenter Phase Iia Study

Cancer chemotherapy may be associated with a high incidence of nausea and vomiting, particularly when highly emetogenic antineoplastic drugs are used. Uncontrolled emesis can profoundly impact on the patient's quality of life and ability to survive, by causing dehydration, electrolyte imbalance, malnutrition and treatment discontinuation. The ABVD regimen (Adriamycin, Bleomycin, Vinblastine and Dacarbazine) is considered the standard of care for first-line treatment of Hodgkin's Lymphoma. Among these drugs, dacarbazine and adriamycin are the most emetogenic, being classified as highly and moderately emetogenic chemotherapy, respectively. NEPA is the first fixed antiemetic combination composed by the pharmacologically and clinically distinct 5HT3 receptor antagonist (5HT3-RA) palonosetron and the highly selective Neurokinin1/Substance P receptor antagonist (NK1-RA). A single dose of NEPA per chemotherapy cycle acts on the principal pathways involved in the mechanisms controlling nausea and vomiting in a synergistic way with an appropriate half-life to cover both the acute (0-24 hours from chemotherapy) and delayed (25-120 hours) phase. In this open label multicenter study, chemo-naïve Hodgkin's Lymphoma patients who were addressed to receive their first cycle of ABVD regimen (2 doses in 28 days, on days 1 and 15) were given a single administration of NEPA plus 4 mg dexamethasone. The primary endpoint was complete response (CR), defined as no emesis and no rescue medication during the overall phase (0-120 hours) on the first dose of the first ABVD cycle. A total of 77 patients were evaluated. According to the adopted Fleming one-stage design, the primary endpoint of this study was achieved. Indeed, the number of the complete responders for the overall phase among the first 70 consecutive patients was 66, which is greater than the pre-determined cut-off of 46, representing the minimum frequency of responders for which the treatment is considered effective. In addition to the primary efficacy endpoint, several additional endpoints were evaluated. The CR values were 93.5% for the acute phase, 81.8% for the delayed phase and 80.5% for the overall phase, while Complete Control (CR with no more than mild nausea) were achieved in the 93.5%of patients in the acute phase, 76.6% in the delayed phase and 75.3% in the overall phase (Figure 1A). Also, levels of no significant nausea (no more than mild nausea) were 94.6% for the acute phase, 83.1% for the delayed phase and 81.8% for the overall phase (Figure 1B). This study demonstrated the efficacy of NEPA plus dexamethasone in preventing the nausea and vomiting induced by the highly emetogenic ABVD regimen. Disclosures Abruzzese: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Di Renzo:BerGenBio ASA: Research Funding. Flenghi:takeda: Consultancy; Roche: Consultancy; janssen-cilag: Consultancy; teva: Consultancy; Servier Italia: Consultancy. Cantonetti:Vifor: Consultancy; Mundipharma: Consultancy; Roche: Consultancy; Takeda: Consultancy.

Patient-related Risk Factors for Nausea and Vomiting With Standard Antiemetics in Patients With Cancer Receiving Carboplatin: A Retrospective Study

PurposeThis study aimed to identify patient-related risk factors for chemotherapy-induced nausea and vomiting (CINV) in patients with cancer receiving carboplatin in addition to standard antiemetics, using real-world data. MethodsIn this single-center, observational study, data from electronic medical records of consecutive patients with solid tumors who had received their first cycle of a carboplatin-based regimen and were treated with a 2- or 3-drug combination of antiemetics from January 2014 to January 2019 at Toranomon Hospital were retrospectively analyzed. The primary end point was the occurrence of a complete response (CR) within 5 days after the first cycle, which was defined as no vomiting and no use of rescue medication for CINV. A receiver operating characteristic curve, univariable, and multivariable logistic regression analyses were used. FindingsA total of 314 patients were evaluated in this study. The proportion of patients who had a CR in the overall, acute, and delayed phases was 76.8% (n = 241), 98.7% (n = 310), and 77.4% (n = 243), respectively. Similar to univariable logistic regression analysis, multivariable logistic regression analysis revealed that age ≥70 years and total dexamethasone dose ≥14.6 mg were significantly associated with a non-CR in the overall phase, whereas female sex, history of habitual alcohol intake, and history of smoking were not associated with a non-CR in the overall phase. ImplicationsOur study findings suggest that a patient age of <70 years and a total dexamethasone dose of <14.6 mg are high-risk factors for carboplatin-induced CINV