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Despite the widespread use of immuno-oncological and targeted therapy in the treatment of malignant tumors, in real clinical practice the role of chemotherapy is still significant, used both in mono regimen and in combination with other antitumor drugs. Cytostatics cause a wide range of adverse events, which are often the cause of dose reduction, cyclical disorders, or even discontinuation of therapy. One of the most common symptoms is chemotherapy-induced nausea and vomiting which affect not only the quality of life, but also the results of treatment. It is important to address these issues from prevention and treatment perspectives so that patients remain committed to their treatment regimens. Since nausea and vomiting induced by chemotherapy are classified into 5 different types, the main medications for prevention and treatment include 5-hydroxytryptamine type 3 (5-HT3) and neurokinin-1 (NK1) receptor antagonists and corticosteroids. Simultaneous use of drugs from the groups of second-generation NK1 receptor blockers and 5-HT3 receptor blockers, for example: netupitant + palonosetron in combination with corticosteroids, makes it possible to achieve maximum antiemetic effect, even with the most emetogenic antitumor treatment regimens.

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma, for which cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab(R–CHOP) is one of the standard regimens. Given that R–CHOP is highly emetogenic, chemotherapy-induced nausea and vomiting (CINV) prevention is clinically important. However, there is a paucity of studies focusing on these patients. This study aimed to ascertain the effectiveness of an oral fixed-dose combination of netupitant and palonosetron (NEPA) in preventing CINV in patients with DLBCL undergoing first-line R-CHOP chemotherapy. Seventy patients were enrolled in this single-center prospective non-comparative study conducted between November 2020 and May 2023 in South Korea. NEPA was administered 1 h prior to chemotherapy initiation on day 1. The primary endpoint of the study was the complete response rate (no emesis, and no rescue medication) during the acute, delayed, and overall phases, which were assessed over a period of 120 h post-chemotherapy. The complete response rates for NEPA were 90.0% [95% CI 80.5, 95.9] for the acute phase, 85.7% [95% CI 75.3, 92.9] for the delayed phase, and 84.3% [95% CI 73.6, 91.9] for the overall phase, with no-emesis rates (acute: 97.1% [95% CI 97.1, 99.7], delayed: 95.7% [95% CI 88.0, 99.1], overall: 92.9% [95% CI 84.1, 97.6]). NEPA was well tolerated with no severe treatment-emergent adverse events. NEPA exhibited substantial efficacy in mitigating CINV in DLBCL patients undergoing R–CHOP chemotherapy, demonstrating high CR and no-emesis rates, and favorable safety profiles.

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.

Considering the frequent use of netupitant in polytherapy, the elucidation of its oxidative metabolization pattern is of major importance. However, there is a lack of published research on the redox behavior of this novel neurokinin-1 receptor antagonist. Therefore, this study was performed to simulate the intensive hepatic biotransformation of netupitant using an electrochemically driven method. Most of the known enzyme-mediated reactions occurring in the liver (i.e., N-dealkylation, hydroxylation, and N-oxidation) were successfully mimicked by the electrolytic cell using a boron-doped diamond working electrode. The products were separated by reversed-phase high-performance liquid chromatography and identified by high-resolution mass spectrometry. Aside from its ability to pinpoint formerly unknown metabolites that could be responsible for the known side effects of netupitant or connected with any new perspective concerning future therapeutic indications, this electrochemical process also represents a facile alternative for the synthesis of oxidation products for further in vitro and in vivo studies.

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 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: The objective was to evaluate the cost-effectiveness of NEPA, an oral fixed combination netupitant (NETU, 300 mg) and palonosetron (PA, 0.5 mg) compared with aprepitant and palonosetron (APPA) or palonosetron (PA) alone, to prevent chemotherapy-induced nausea and vomiting (CINV) in patients undergoing treatment with highly or moderately emetogenic chemotherapy (HEC or MEC) in the UK. Scope: A systematic literature review and meta-analysis were undertaken to compare NEPA with currently recommended anti-emetics. Relative effectiveness was estimated over the acute (day 1) and overall treatment (days 1–5) phases, taking complete response (CR, no emesis and no rescue medication) and complete protection (CP, CR and no more than mild nausea [VAS scale

Vito Lorusso National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Bari, Italy Abstract: As recommended by most recent antiemetic guidelines, the optimal prophylaxis of chemotherapy-induced nausea and vomiting (CINV) requires the combination of 5-HT3 receptor antagonist (RA) with an NK1-RA. Moreover, the major predictors of acute and delayed CINV include: young age, female sex, platinum- or anthracycline-based chemotherapy, nondrinker status, emesis in the earlier cycles of chemotherapy, and previous history of motion/morning sickness. Despite improved knowledge of the pathophysiology of CINV and advances in the availability of active antiemetics, an inconsistent compliance with their use has been reported, thereby resulting in suboptimal control of CINV in several cases. In this scenario, a new antiemetic drug is now available, which seems to be able to guarantee better prophylaxis of CINV and improvement of adherence to guidelines. In fact, netupitant/palonosetron (NEPA) is a ready-to-use single oral capsule, combining an NK1-RA (netupitant) and a 5-HT3-RA (palonosetron), which is to be taken 1 hour before the administration of chemotherapy, ensuring the coverage from CINV for 5 days. We reviewed the role of NEPA in patients at high risk of CINV receiving highly emetogenic chemotherapy. In these patients, NEPA plus dexamethasone, as compared to standard treatments, achieved superior efficacy in all primary and secondary end points during the acute, delayed, and overall phases, including nausea assessment. Moreover, these results were also achieved in female patients receiving anthracycline plus cyclophosphamide-based chemotherapy. NEPA represents a real step forward in the prophylaxis of CINV. Keywords: NEPA, netupitant, NK1, CINV, vomiting, risk factors

Piotr K JanickiDepartment of Anesthesiology and Perioperative Medicine, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA, USAPurpose: The purpose of this review is to summarize and discuss the recently published data (both original studies and reviews) on the oral medication NEPA, consisting of netupitant (a neurokinin-1 receptor antagonist [NK1RA], 300 mg dose) and palonosetron (5-hydroxytryptamine [serotonin or 5HT] type 3 receptor antagonist [5HT3RA], 0.5 mg dose), in the prevention of the acute and delayed nausea and vomiting in patients receiving highly or moderately emetogenic chemotherapy.Methods: This review was based on the very limited number of available published trials consisting of two Phase III studies and one Phase II dose-selecting trial.Results: These studies demonstrated some therapeutic benefits of NEPA over related chemotherapy-induced nausea and vomiting (CINV) prophylaxis management, as well as its beneficial safety profile. In particular, compared with single-dose 0.5 mg palonosetron, the complete response rates for all phases of CINV for the first cycle of highly emetogenic chemotherapy (with cisplatin), as well as anthracycline–cyclophosphamide-based moderately emetogenic chemotherapy, were significantly higher for single-dose NEPA. The high efficacy of NEPA in terms of prevention of CINV continued throughout repeated cycles of highly and moderately emetogenic therapies.Conclusion: It is currently recommended that patients who are administered highly emetogenic chemotherapy regimens should obtain a three-drug combination consisting of NK1RA, 5HT3RA, and dexamethasone. The recently available oral combination of NEPA plus dexa­methasone provides an additional pharmacological management option that could be considered in this scenario.Keywords: chemotherapy-induced nausea and vomiting, palonosetron, netupitant, NEPA, safety, pharmacology, outcomes

Introduction. Tachykinins potently contract the isolated urinary bladder from a number of animal species and play an important role in the regulation of the micturition reflex. On the guinea-pig isolated urinary bladder we examined the effects of a new potent and selective NK1 receptor antagonist (netupitant) on the contractions induced by a selective NK1 receptor agonist, SP-methylester (SP-OMe). Moreover, the effects of netupitant and another selective NK1 antagonist (L-733,060) were studied in anesthetized guinea-pigs using two experimental models, the isovolumetric bladder contractions and a model of bladder overactivity induced by intravesical administration of acetic acid (AA). Methods and Results. Detrusor muscle strips were mounted in 5 mL organ baths and isometric contractions to cumulative concentrations of SP-OME were recorded before and after incubation with increasing concentrations of netupitant. In anesthetized female guinea-pigs, reflex bladder activity was examined under isovolumetric conditions with the bladder distended with saline or during cystometry using intravesical infusion of acetic acid (AA). After a 30 min stabilization period, netupitant (0.1-3 mg/kg, i.v.) or L-733,060 (3-10 mg/kg, i.v.) were administered. In the detrusor muscle, netupitant produced a concentration-dependent inhibition (mean pKB = 9.24) of the responses to SP-OMe. Under isovolumetric conditions, netupitant or L-733,060 reduced bladder contraction frequency in a dose-dependent manner, but neither drug changed bladder contraction amplitude. In the AA model, netupitant dose-dependently increased intercontraction interval (ICI) but had no effect on the amplitude of micturition (AM). L-733,060 dose-dependently increased ICI also but this effect was paralleled by a significant reduction of AM. Conclusion. Netupitant decreases the frequency of reflex bladder contractions without altering their amplitude, suggesting that this drug targets the afferent limb of the micturition reflex circuit and therefore may be useful clinically in treating bladder overactivity symptoms.