Chemotherapy-induced Nausea And Vomiting In Patients Research Articles

Efficacy and safety of netupitant/palonosetron in preventing nausea and vomiting in diffuse large B cell lymphoma patients undergoing R–CHOP chemotherapy

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.

A nurse-led multidomain intervention to improve the management of chemotherapy-induced nausea and vomiting in patients with head and neck cancers: A randomized controlled trial

PurposeThis study aimed to investigate the effect of a nurse-led multidomain intervention on chemotherapy induced nausea and vomiting (CINV) in patients with head and neck squamous cell carcinomas (HNSCC). MethodsNinety-two HNSCC patients who received cisplatin-based chemotherapy were divided into intervention group (n = 45) and control group (n = 47). The control group received usual care of CINV, which consisted of administration of antiemetics according to physicians' preference, education about CINV control and dietary recommendations provided by primary nurses. The intervention group received nurse-led, evidence-based multidomain management, including nurse-led CINV risk factors assessment, education on prevention and control of CINV, antiemetics following guidelines, dietary strategies, and relaxation therapy. The number of patients who experienced CINV was collected. The severity of CINV was graded according to the Common Terminology Criteria for Adverse Events v3.0. The influence of CINV on patient's quality of life was assessed by the Functional Living Index-Emesis (FLIE). ResultsThe incidence and the severity of nausea and vomiting in the intervention group were significantly lower than those in the control group within 5 days after chemotherapy, and the scores of the dimension of nausea and vomiting in the intervention group were significantly higher than those in the control group [63.00 (50.00–63.00) vs 40.00(28.00–63.00), 63.00(63.00–63.00) vs 63.00 (43.00–63.00)], the differences were statistically significant (P < 0.05). ConclusionsNurse-led multidomain intervention can reduce the incidence and the severity of CINV in patients with HNSCC who were treated with cisplatin-based chemotherapy, and thus reduced the influence of CINV on patients' quality of life. The clinical trial registration numberNCT05792228.

Retrospective Evaluation of a Dexamethasone Sparing Antiemetic Regimen: An Antiemetic Prophylaxis Study on NEPA (Netupitant Plus Palonosetron) for Preventing Chemotherapy-Induced Nausea and Vomiting (CINV) in Cancer Patients.

Background Corticosteroids, specifically dexamethasone (DEX), have been extensively utilized for the prevention of chemotherapy-induced nausea and vomiting (CINV). However, their usage is associated with a range of adverse events. In contrast, the combination of NetupitantPlus Palonosetron (NEPA) with a single dose of DEX provides comparable efficacy in preventing CINV over a five-day period following chemotherapy administration. This regimen offers the advantage of reducing the need for additional doses of DEX, particularly in the high-risk setting of HEC (Highly emetic chemotherapy). Objective To evaluate dexamethasone sparing anti-emetic regimen (single dose dexamethasone with NEPA) for prophylaxis of CINV in patients receiving HEC. Methodology This is a retrospective, observational, real-world, single-center study including data of 69 patients who received high-dose emetogenic chemotherapy and were administered DEX (8 or 12 mg) on day 1, with no dose ofDEX on days 2, 3, and 4, combined with an oral combination of tablet netupitant 300 mg and palonosetron 0.5 mg. NEPA was taken orally an hour prior to the start of the HEC cycle. The primary efficacy endpoint was complete response (CR) which is defined as no nausea, emesis, or no rescue medication during the Acute (< 24 hours) and Delayed Phase (25-120 hours) of chemotherapy. Results The overall CR achieved in the acute and delayed phase for vomiting is 100% at all four follow-ups. The CR achieved in the acute phase is 95.7% whereas 98.6% of patients showed CR in the delayed phase respectively. No patient required any rescue medication. No acute and delayed phase of vomiting was reported. Conclusion A simplified regimen of NEPA plus single-dose DEX offers effective CINV prevention throughout five days post-chemotherapy with the advantage of sparing patients additional doses of DEX in the high-emetic-risk setting chemotherapy.

Prevention of CINV in Patients with Multiple Myeloma or Lymphoma Undergoing Hematopoietic Stem Cell Transplantation: NEPA Versus Ondansetron. a Monocentric Real-Life Experience

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) are adverse events that compromise quality of life and treatment compliance in patients undergoing autologous hematopoietic stem cell transplantation (ASCT). Polychemotherapy regimens, used as conditioning regimens for ASCT in lymphomas, and high-dose melphalan (≥140 mg/mq), used in multiple myeloma (MM), have high emetogenic risk. Control of CINV is difficult and there is no uniformity for its prophylaxis. Antiemetic guidelines recommend, for prophylaxis, co-administration of a triplet regimen of a serotonine (5-HT3) receptor antagonist (RA), as Ondansetron, a neurokinin-1 RA, and dexamethasone. Netupitant-Palonosetron (NEPA), an oral formulation derived from the combination of Netupitant (NK1-RA) and Palonsetron, has been approved as prophylaxis of CINV but its experience in the stem cell transplant setting is still limited. AIMS: The primary aim of this study was to compare the efficacy of Ondansetron versus NEPA in terms of reduction of CINV in patients affected by lymphoma or MM who undergone ASCT. The secondary aims included comparing the duration of CINV, based on the use of Ondansetron or NEPA, and their safety profile in terms of reduction of extrahaematological toxicity (as mucositis or diarrhea). METHODS: In this retrospective monocentric study, we enrolled 76 patients (48 with MM and 28 with lymphoma), who underwent ASCT between March 2021 and March 2022. All patients with MM received high dose of melphalan, those with lymphoma received FEAM. Regarding antiemetics patients were divided according to whether they received NEPA or Ondansetron . Patients' characteristics are in Table 1. RESULTS: Among all, fifty patients (65%) reported CINV of any grade. In particular, the group experiencing CINV included about half of patients treated with NEPA (56%) and almost all those treated with Ondansetron (91%). Among the 26 patients who didn't report CINV (35%), the majority received NEPA (92%) (P = 0.0032) (Fig. 1a). Focusing on patients with MM, 33 experienced CINV (68%), and they were 59% of MM patients treated with NEPA and 93% of those treated with Ondansetron. Fifteen patients did not experience CINV (32%) and almost all of them (93%) had been treated with NEPA (P = 0.037) (Fig. 1b). Sixty-one percent of the 28 patients with lymphoma reported CINV (P= 0.1914) (Fig. 1c). Mean duration of CINV was significantly shorter for patients treated with NEPA than for those treated with Ondansetron (4.8 days vs 9.2 days) (P= 0.002) (Fig. 1d). Regarding extraematological toxicity of chemotherapy, as mucositis and diarrhea, we didn't find any significant difference between the two groups of patients. Regarding the outcome to NEPA, complete response rate (no emesis, no rescue medication) was 37% during overall phases of CINV, 28% of patients had complete control (complete response with no more than mild nausea) and 31% had uncontrolled nausea. Conversely, in the Ondansetron group, only 5% of patients had complete response and 95% had uncontrolled nausea (Fig. 1e). All patients with uncontrolled nausea required a rescue therapy. According to CTCAE, 69% of patients receiving NEPA had grade 1 nausea and 6% had none, while all patients receiving Ondansetron had CINV and 85% of them had grade 2 nausea. CONCLUSIONS: In our experience, NEPA has shown superiority in the prevention of CINV, in highly emetogenic regimens in both patients with myeloma or lymphoma, with advantages on the severity and the duration of CINV. Given the high burden of CINV in the whole population analyzed in the study, regardless of the antiemetic used, it would be useful to identify patients at greatest risk and standardize CINV prophylaxis and treatment protocols depending on the different chemotherapy regimens and their emetogenic risk.

Oral Tetrahydrocannabinol (THC):Cannabinoid (CBD) Cannabis Extract Adjuvant for Reducing Chemotherapy-Induced Nausea and Vomiting (CINV): A Randomized, Double-Blinded, Placebo-Controlled, Crossover Trial.

To evaluate the effects of tetrahydrocannabinol (THC):cannabinoid (CBD) (1:1) oil in reducing chemotherapy-induced nausea and vomiting (CINV) in gynecologic cancer patients who received moderate-to-high emetogenic chemotherapy. This was a randomized, double-blinded, crossover and placebo-controlled trial. The study was conducted at the Gynecologic Oncology Units, Bhumibol Adulyadej Hospital (BAH), Royal Thai Air Force, Bangkok, Thailand, between August and November 2022. Participants had gynecologic cancer and received moderate-to-high emetogenic chemotherapy. Subjects were randomized and divided into two groups (A and B) based on the block of four randomization method. In the first cycle, groups A and B received THC:CBD extract oil 1:1 (TCEO) and placebo before chemotherapy administration. In the second cycle, groups A and B received placebo and TCEO before chemotherapy administration. Both groups received per protocol antiemetic medication during chemotherapy. Nausea score and side effects were recorded. A total of 60 cases were recruited. After exclusion, 54 cases were included in the study. The mean age of participants was 54.4 years. The mean body mass index (BMI) was 26.5 kg/m2. Fifty-nine (21/54) percent cases were the advanced stages of cancer. The nausea score of TCEO and placebo groups were 2.11 and 2.99, respectively (P < 0.05). More than half of the participants (36/54) reported dizziness and sedation side effects. Dry mouth, confusion, anxiety, and palpitation of both groups were comparable. The cannabinoid extract (THC:CBD) was an appropriate adjuvant agent to reduce CINV in patients with gynecologic cancer who received high-emetogenic chemotherapy. Dizziness and sedation were the major side effects.

Prolonged usage of fosaprepitant for prevention of delayed chemotherapy-induced nausea and vomiting(CINV) in patients receiving highly emetogenic chemotherapy

BackgroundEven though chemotherapy-induced nausea and vomiting (CINV) can be well controlled in the acute phase, the incidence of delayed CINV remains high. In this study, we intend to investigate whether prolonged use of NK-1 receptor antagonist (RA) in addition to 5-HT3 RA and dexamethasone (DEX) was more effective in preventing delayed CINV.MethodsThis randomised, open-label, controlled study was designed to compare the efficacy and safety of fosaprepitant 150 mg given on days 1,3 (prolonged group) versus on day 1 (regular group) in patients receiving highly emetogenic chemotherapy (HEC). All patients also treated with palonosetron on day 1 and DEX on days 1–3. The primary endpoint was the incidence of delayed nausea and vomiting. The second endpoint was AEs. All the above endpoints were defined according to CTCAE 5.0.ResultsSeventy-seven patients were randomly assigned to prolonged group and seventy-nine to regular group. Prolonged group demonstrated superiority in controlling delayed CINV to regular group, with statistically significant lower incidence of nausea (6.17% vs 12.66%, P = 0.0056), and slightly lower incidence of grade 1 vomiting (1.62% vs 3.80%, P = 0.0953) in the delayed phase. In addition, prolonged use of fosaprepitant was safe. No significant difference was found between the two groups regarding constipation, diarrhea, hiccough, fatigue, palpitation and headache in delayed phase.ConclusionsProlonged use of fosaprepitant can effectively and safely prevent delayed CINV in patients receiving HEC.

Aldehyde dehydrogenase 2 rs671 genetic polymorphisms are associated with chemotherapy-induced nausea and vomiting

To investigate the correlation between aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms and chemotherapy-induced nausea and vomiting (CINV). A total of 90 Chinese patients with malignant tumors receiving chemotherapy for the first time were recruited in this study. The occurrence of CINV was observed within 120 h after treatment with docetaxel and cis-platinum chemotherapy (DP regimen). The data of the patients (including age, gender, tumor stage, habitual alcohol consumption, motion sickness, morning sickness, and average sleep time prior to chemotherapy) were collected through a questionnaire. ALDH2 rs671 polymorphisms of the patients were analyzed using a multiple single nucleotide polymorphism genotyping, and the Hardy-Weinberg equation was used for genetic linkage analysis. The correlations between the factors including ALDH2 rs671 polymorphisms and the occurrence of CINV were analyzed. The incidence of CINV was 48.9% among the patients receiving their first chemotherapy with DP regimen. Univariate analysis indicated that the genetic polymorphisms of ALDH2 rs671 were significantly correlated with the occurrence of CINV (P < 0.05). Multivariate logistic analysis indicated that ALDH2 rs671 mutation (OR: 3.019, 95% CI: 1.056-8.628, P < 0.05) and average sleep time prior to chemotherapy no longer than 6 h (OR: 2.807, 95% CI: 1.033-7.628, P < 0.05) were risk factors for CINV in patients with malignant tumors receiving the first chemotherapy with DP regimen. ALDH2 gene mutation at rs671 is a risk factor contributing to the occurrence of CINV, and understanding of the underlying mechanism may help to more effectively control the occurrence of CINV.

Treatment of breakthrough and prevention of refractory chemotherapy-induced nausea and vomiting in pediatric cancer patients: Clinical practice guideline update.

This clinical practice guideline update provides recommendations for treating breakthrough chemotherapy-induced nausea and vomiting (CINV) and preventing refractory CINV in pediatric patients. Two systematic reviews of randomized controlled trials in adult and pediatric patients informed the recommendations. In patients with breakthrough CINV, escalation of antiemetic agents to those recommended for chemotherapy of the next higher level of emetogenic risk is strongly recommended. A similar recommendation to escalate therapy is made to prevent refractory CINV in patients who did not experience complete breakthrough CINV control and are receiving minimally or low emetogenic chemotherapy. A strong recommendation to use antiemetic agents that controlled breakthrough CINV for the prevention of refractory CINV is also made.

Fosnetupitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Short Review and Clinical Perspective.

Chemotherapy-induced nausea and vomiting (CINV) is often ranked by patients as one of the most distressing and feared consequences of chemotherapy. The novel neurokinin-1 (NK1) receptor antagonist fosnetupitant, a phosphorylated prodrug formulation of netupitant, was approved in Japan in 2022. Fosnetupitant is one of the standard treatments for the prevention of CINV in patients who are receiving highly (any treatment where CINV occurs in more than 90% of patients) or moderately (where CINV occurs in 30-90% of patients) emetogenic chemotherapies. The aim of this commentary is to describe the mechanism of action, tolerability, and antiemetic efficacy of single-agent fosnetupitant in the prevention of CINV, and to discuss its clinical application, in order to aid optimal use.

Abstract PD8-01: PantoCIN: Pantoprazole’s effectiveness as prophylaxis against delayed Chemotherapy-Induced Nausea and Vomiting (CINV) in patients receiving adjuvant or neoadjuvant breast cancer chemotherapy

Abstract Background: Rates of delayed CINV remain high at over 50% following adjuvant chemotherapy for breast cancer, despite the use of multiple antiemetics. Delayed CINV is complex, distressing to patients and it’s incidence is underestimated by physicians. Anti-emetics used with early breast cancer chemotherapy are often directed against acute rather than delayed CINV. Chemotherapy is virtually eliminated from the circulation prior to the delayed phase (24-120 hours post-chemotherapy), suggesting the etiologies for acute and delayed CINV may differ. Chemotherapy and steroids can alter the gastric environment and acid secretion, while chemotherapy can cause gastroesophageal mucositis. We hypothesized that the altered gastric environment, combined with disrupted gastroesophageal mucosa, could contribute to delayed nausea in a proportion of patients. Anecdotal experience suggested proton pump inhibitors, such as Pantoprazole, reduced symptoms in this setting. Methods: This study incorporated a double-blinded crossover design to determine whether Pantoprazole would reduce the incidence of delayed CINV in patients receiving adjuvant, or neoadjuvant breast cancer chemotherapy. Patients were randomized to either pantoprazole or placebo from Day 1-5 after cycle 1, changing to the other intervention for cycle 2. CINV symptoms during the delayed phase were assessed using the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool and recorded in real time by patients using the PantoCIN ePRO application. With 160 patients, this approach had an 80% power to detect a statistically significant effect (one-sided α (type 1) error of 0.025) of Pantoprazole, if the true effect of Pantoprazole is a 10% reduction in the rates of any delayed CINV compared to placebo. The primary endpoint was the proportion of patients with complete absence of both nausea and vomiting during days 2-5, with severity of CINV and patient preference for intervention described as secondary endpoints. Results: 160 patients were recruited between June 2019 and October 2021, from 10 different cancer centers in New Zealand. Primary statistical analysis has shown a significant reduction in absolute CINV with pantoprazole as the primary end point, with incidence of any CINV symptoms reducing from 61.0% to 49.6% (OR=1.8, 95% confidence interval (1.0 to 3.3); p-value=0.04), in patients with full data. There was also a clear preference for patients to prefer the blinded pantoprazole arm of the 2 cycles of treatment under study, with the proportion of participants who preferred pantoprazole to placebo being 49% and the proportion who preferred placebo to pantoprazole was 25.2%, (difference in proportions 23.8% and 95% confidence interval 12.4 to 35.2; p=0.0017). Conclusion: CINV is a common and distressing complication of early breast cancer chemotherapy, which persists despite the use of a range of current antiemetics. Pantoprazole is a cheap, well-tolerated agent without significant drug interactions, which clearly ameliorates this symptom in a significant proportion of patients and should be considered as a standard prophylactic intervention. Citation Format: Navin Wewala, Katrina Sharples, Yujin Kim, Sarah Benge, Robert Cartwright, Louise Clement, Ying Huang, Richard Isaacs. PantoCIN: Pantoprazole’s effectiveness as prophylaxis against delayed Chemotherapy-Induced Nausea and Vomiting (CINV) in patients receiving adjuvant or neoadjuvant breast cancer chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD8-01.

Effect of Mirtazapine for the Prevention of Nausea and Vomiting in Patients With Thoracic Cancer Receiving Platinum-based Chemotherapy.

Mirtazapine, which exerts an antagonistic effect on 5-hydroxytryptamine type 5-HT2A, 5-HT2C, 5-HT3 and H1 receptors, is considered useful for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). This study investigated the efficacy and safety of mirtazapine for the prevention of CINV in patients with thoracic cancer receiving platinum-based chemotherapy. A retrospective cohort study was conducted in patients with thoracic cancer receiving platinum-based chemotherapy with 15 mg mirtazapine once daily as a prophylactic antiemetic drug between January 2014 and December 2021. The effects of mirtazapine added to the standard antiemetic regimen for the prevention of CINV were evaluated in patients who had poor control of CINV in a preceding cycle and in patients who received the standard antiemetic therapy plus mirtazapine from their first cycle. A total of 35 patients were evaluated. Of these, 14 had poor control of CINV in a preceding cycle and received the standard antiemetic therapy plus mirtazapine in the next cycle. The rate of complete response in the delayed period in these patients was significantly improved from the preceding cycle to the next cycle (35.7% vs. 85.7%, p=0.018). In contrast, the other 21 patients had received the standard antiemetic regimen plus mirtazapine from the first cycle. The rate of complete response in the delayed period in these patients receiving the triplet antiemetic regimen plus mirtazapine as part of a cisplatin-based or carboplatin-based regimen and in patients receiving a doublet antiemetic regimen plus mirtazapine in a carboplatin-based regimen was 100%, 85.7% and 100%, respectively. No severe adverse events, including somnolence, were observed with the addition of mirtazapine. The addition of mirtazapine to the standard antiemetic regimen for CINV may be beneficial with acceptable safety when administered in association with platinum-based regimens to patients with thoracic cancer.

A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of olanzapine plus triple antiemetic regimen for the prevention of multiday highly emetogenic chemotherapy-induced nausea and vomiting (OFFER study).

Evidence supports prophylactic use of olanzapine for the treatment of chemotherapy-induced nausea and vomiting (CINV). However, most studies to date have focused on patients with single-day highly emetogenic chemotherapy (HEC). Currently, administration of antiemetic therapies for nausea and vomiting induced by multiday chemotherapy regimens remains a challenge. In this study, we evaluated the efficacy of olanzapine combined with triple antiemetic therapy for the prevention of CINV in patients receiving multiday chemotherapy. We performed a randomized, double-blind, placebo-controlled phase 3 trial in 22 hospitals. Eligible patients were between 18 and 75 years old, were diagnosed with malignant solid tumors, and they had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. All the study participants were scheduled to be treated with chemotherapy regimens containing 3-day cisplatin (3-day total dose ≥75mg/m2). Randomization was computer generated and stratified by gender and chemotherapy treatment history. Allocation was done via an interactive web response system. Enrolled patients were randomly assigned 1:1 to receive either 5mg olanzapine or placebo orally before bedtime for 5 days combined with intravenous fosaprepitant (150mg) 1h before the administration of cisplatin on day 1, ondansetron hydrochloride intravenously, and dexamethasone orally 30min before cisplatin from days 1 to 3. Dexamethasone was also administered at the same time on days 4 and 5. The primary endpoint was the proportion of subjects with complete response (no vomiting and no rescue therapy) within the overall phase (days 1-8) after starting chemotherapy. Baseline plasma concentrations of P-substance and 5-HT were measured for exploratory analysis. This study was registered at ClinicalTrials.gov, number NCT04536558. Between December 2020 and September 2021, 349 patients with malignant solid tumors were enrolled in the study, with 175 participants randomly assigned to receive olanzapine and 174 participants assigned to receive placebo. The proportion of patients who achieved a complete response in the overall phase was significantly higher in the olanzapine group than in the placebo group (69% vs. 58%, P=0.031). A complete response benefit was observed in the olanzapine group versus the placebo group in almost all the subgroups. Four factors were considered significantly associated with complete response in multivariable analysis: treatment group, gender, baseline plasma concentration of 5-HT, and prior radiotherapy. All the reported adverse events associated with olanzapine administration were grades 1 and2. Olanzapine (5mg) combined with fosaprepitant, ondansetron, and dexamethasone was better than triple antiemetic therapy alone for patients receiving multiday chemotherapy regimens. Based on these results, the four-drug combination should be recommended as the best antiemetic regimen given to patients receiving multiday cisplatin-based chemotherapy and baseline plasma concentration of 5-HT may be used to identify individuals who are prone to CINV. However, all these findings need to be further validated in future studies. Jiangsu Hansoh Pharmaceutical Group Co., Ltd. provided research grant and study drugs for this investigator-initiated study.

The Efficacy and Safety of Adding Olanzapine to Triple Drugs Regimen to Prevent Chemotherapy-induced Nausea and Vomiting: A systematic Review and Meta-analysis of RCTs

Chemotherapy-induced nausea and vomiting (CINV) is a complication of highly emetogenic chemotherapy (HEC) agents. The present meta-analysis was conducted to quantify and analyze the efficacy and safety of adding olanzapine to a Neurokinin Receptor Antagonist (NKRA) based triple-drug regimen in preventing HEC-induced CINV. Electronic database searches in PUBMED and Cochrane library was conducted using MeSH search terms “olanzapine” and “chemotherapy-induced nausea and vomiting.” Randomized or cross-over trials comparing the efficacy of “olanzapine + NKRA based triple-drug regimen” vs. “placebo + NKRA based triple-drug regimen” in patients of age &gt; 18 years with any malignancy receiving HEC were considered under inclusion criteria. Complete Response (CR) for the delayed (25–120 h) phase of CINV in patients receiving HEC agents was the primary outcome measure analyzed. Outcome measures were estimated by calculating the Risk Difference (RD) values and their 95% Confidence Intervals (CI). The Mantel-Haenszel method and both fixed and random effect models were used in the analysis by Revman 5.4.1 soft- ware. An additional 14% (RD: 0.14, 95% CI: 0.09 to 0.19) of patients treated with olanzapine + triple-drug regimen had a statistically significant higher CR in the delayed phase when compared to placebo + NKRA-based triple-drug regimen. Adding olanzapine at 10mg to the triple-drug regimen significantly improves delayed phase CR rates by 16% and delayed phase ‘no significant nausea’ rates by 30%. Results need to be interpreted cautiously in the background of response variations and limited trials included in our analysis

Concomitant palonosetron ameliorates cisplatin-induced nephrotoxicity, nausea, and vomiting: a retrospective cohort study and pharmacovigilance analysis

BackgroundCisplatin (CDDP)-induced nephrotoxicity is the most important complication of CDDP treatment. 5-Hydroxytryptamine type 3 receptor antagonists (5-HT3RAs) are widely used to prevent chemotherapy-induced nausea and vomiting (CINV). However, in patients with the triple antiemetic (neurokinin-1 receptor antagonist, 5-HT3RA, and dexamethasone) therapy, the advantage of palonosetron in comparison with other 5-HT3RAs on CDDP-induced nephrotoxicity and CINV remains unclear. In the present study, we investigated the effect of palonosetron on CDDP-induced nephrotoxicity and CINV in patients with the triple antiemetic therapy by a retrospective cohort study and a pharmacovigilance analysis.MethodsWe retrospectively analyzed the effect of 5-HT3RAs on the development of nephrotoxicity and CINV in 110 patients who received CDDP, fluorouracil, and triple antiemetic therapy for the treatment of esophageal cancer. Moreover, the effect of 5-HT3RAs on CDDP-induced nephrotoxicity was validated in patients with the triple antiemetic therapy using the Japanese Adverse Drug Event Report (JADER) database.ResultsIn a retrospective study, the incidence of nephrotoxicity (≥ grade 1) in patients receiving palonosetron (18%) was significantly lower than that in patients receiving ramosetron (another 5-HT3RA) (36%, p = 0.044). Moreover, severe nephrotoxicity ≥ grade 3 was observed in one patient treated with ramosetron, whereas hematological toxicity was comparable between the two groups (p = 0.553). Furthermore, the incidence rate of CINV within 120 h following CDDP administration in patients treated with palonosetron (18%) was significantly lower than that in patients receiving ramosetron (39%, p = 0.026). JADER database analyses revealed that the reporting odds ratio of palonosetron for CDDP-induced acute kidney injury was 0.282 (95% confidence interval: 0.169–0.472).ConclusionsThe findings of the present study suggested a greater potential of palonosetron against CDDP-induced nephrotoxicity and CINV than other 5-HT3RAs in patients with the triple antiemetic therapy.

Aprepitant plus palonosetron versus dexamethasone plus palonosetron in preventing chemotherapy-induced nausea and vomiting in patients with moderate-emetogenic chemotherapy: A randomized, open-label, phase 3 trial.

SummaryBackgroundDespite significant progress in the prevention of chemotherapy-induced nausea and vomiting (CINV) by using dexamethasone combined with palonosetron for patients who received moderate-emetogenic chemotherapy (MEC), some of these patients still suffer from CINV. We evaluated whether aprepitant combined with palonosetron can improve the efficacy in the prevention of CINV in patients receiving MEC.MethodsThis was a single-centre, open-label, phase III, randomized controlled trial, which was done at the Sixth Affiliated Hospital of Sun Yat-sen University of China. The registered patients planned to receive mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) but had not received any chemotherapy previously. The patients were randomized in a 1:1 ratio to the aprepitant group (aprepitant 125 mg orally on day 1, 80 mg on day 2-3) and the dexamethasone group (dexamethasone 10 mg intravenously on day 1, 5 mg on days 2 and 3), both groups with palonosetron 0.25 mg intravenously on day 1. The primary endpoint was the proportion of patients who achieved a complete response (CR), defined as the absence of vomiting and no use of rescue medications in the overall phase (0–120 h). The primary outcome and safety were assessed in the modified intention-to-treat population, which excluded all patients who used estazolam within 24 h before registration and those who refused to keep a diary documenting the severity of nausea, frequency of vomiting, and the use of rescue therapy. This trial is registered with ClinicalTrials.gov, NCT02909478.FindingsBetween Sep 1, 2017, and Oct 23, 2019, 320 patients were enrolled, and 315 patients were evaluated. The proportion of patients who achieved CR was significantly higher with aprepitant than that noted with dexamethasone in the overall phase (88.8% vs. 74.2%; P = 0.0010; rate difference, RD 15%, 95% CI, 6% to 23%) and in the delayed phase (25–120 h), 90.6% vs. 75.5%, (P < 0.0001; RD 15%, 95%CI, 7% to 23%). No significant difference of CR rate was observed in the acute phase (0–24 h), 93.8% vs. 93.5%, (P = 0.94; RD 0%, 95% CI, -5% to 6%)). In the overall phase, the incidence of insomnia (P < 0.0010), dyspepsia (P = 0.038), and flushing (P = 0.0010) reported by the patients was significantly higher in the dexamethasone group than that in the aprepitant group.InterpretationAprepitant combined with palonosetron is superior to dexamethasone combined with palonosetron in patients who received the MEC regimen mFOLFOX6 in terms of preventing CINV.FundingThe National Key R&D Program of China (2019YFC1316000) and the National Natural Science Foundation of China (81974369).

POSA159 Cost-Effectiveness of Netupitant/Palonosetron in the Treatment of Chemotherapy-Induced Nausea and Vomiting in the UK

Chemotherapy-induced nausea and vomiting (CINV) is among the most common side-effects reported by cancer patients undergoing chemotherapy. This analysis aimed to evaluate the cost-effectiveness of fixed-combination netupitant/palonosetron (NEPA) compared with other commonly used antiemetic treatments for the prevention of CINV in patients undergoing highly emetogenic chemotherapy (HEC) in the UK.

The Effect of Foot Reflexology on Chemotherapy-Induced Nausea and Vomiting in Patients With Digestive or Lung Cancer: Randomized Controlled Trial.

BackgroundCancer is a chronic disease with an incidence of 24.5 million and 9.6 million deaths worldwide in 2017. Lung and colorectal cancer are the most common cancers for both sexes and, according to national and international recommendations, platinum-based chemotherapy is the reference adjuvant treatment. This chemotherapy can be moderately to highly emetogenic. Despite antiemetic therapy, chemotherapy-induced nausea and vomiting (CINV) may persist. Moreover, cancer patients are increasingly interested in alternative and complementary medicines and have expressed the desire that nonpharmacological treatments be used in hospitals. Among alternative and complementary medicines, foot reflexology significantly decreases the severity of CINV in patients with breast cancer.ObjectiveThe primary aim of this study was to assess the benefits of foot reflexology as a complement therapy to conventional treatments regarding the severity of acute CINV in patients with digestive or lung cancer. The secondary objectives assessed were the frequency and severity of delayed CINV, quality of life, anxiety, and self-esteem.MethodsThis study was conducted between April 2018 and April 2020 in the Hospices Civils de Lyon, France. This was an open-label randomized controlled trial. Participants were randomized into two groups: the intervention group (ie, conventional care with foot reflexology; n=40) and the control group (ie, conventional care without foot reflexology; n=40). Foot reflexology sessions (30 minutes each) were performed on outpatients or inpatients. Eligible participants were patients with lung or digestive cancer with an indication for platinum-based chemotherapy.ResultsThe severity of acute nausea and vomiting was assessed with a visual analog scale during the second cycle of chemotherapy. A significant increase of at least 2 points was observed for the control group (7/34, 21%; P=.001). Across all cycles, the foot reflexology group showed a trend toward less frequent delayed nausea (P=.28), a significantly less frequent consumption of antiemetic drugs (P=.04), and no significant difference for vomiting (P=.99); there was a trend toward a perception of stronger severity for delayed nausea in the control group (P=.39). Regarding quality of life and anxiety, there was no significant difference between the intervention group and the control group (P=.32 and P=.53, respectively).ConclusionsThis study’s results indicate that foot reflexology provides significantly better management of acute nausea severity and decreased consumption of antiemetic drugs in patients with lung or digestive cancer. In order to fulfill patients’ desires to use nonpharmacological treatments and complementary and alternative medicines in hospitals, foot reflexology could be provided as a complementary intervention to conventional antiemetic drugs. Foot reflexology did not result in adverse effects. To assess the benefits of foot reflexology in routine practice, a larger study with several health care centers would be needed with a cluster randomized controlled trial.Trial RegistrationClinicalTrials.gov NCT03508180; https://clinicaltrials.gov/ct2/show/NCT03508180International Registered Report Identifier (IRRID)RR2-10.2196/17232

Efficacy and safety of netupitant/palonosetron combination (NEPA) in preventing nausea and vomiting in non-Hodgkin\u2019s lymphoma patients undergoing to chemomobilization before autologous stem cell transplantation

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

English

BACKGROUND Chemotherapy-induced nausea and vomiting (CINV) is a frequent and feared adverse effect of cancer chemotherapy. International guidelines recommend combinations of 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, dexamethasone, and/or neurokinin-1 (NK1) receptor antagonists for the control of CINV in patients receiving highly emetogenic chemotherapy (HEC) as a part of their treatment. Even though, nausea in delayed period is less controlled and poses a major concern for these patients. METHODS This open label, prospective study was conducted in a rural medical college in Etawah District in Uttar Pradesh, India from November 2017 to November 2018 over a period of 1 year to observe the efficacy of low dose (5 mg OD) olanzapine in combination with standard anti-emetic regimen for the prevention of CINV. Olanzapine is a food and drug administration (FDA) approved antipsychotic drug that has anti-emetic activity and has shown to improve CINV. Low dose olanzapine along with a standard combination of ondansetron, dexamethasone and aprepitant was given to patients receiving highly emetogenic chemotherapy (Cisplatin &gt;70 mg/m2 or doxorubicin-cyclophosphamide combination). CINV was assessed using common toxicity criteria of adverse events (CTCAE) version 5.0. RESULTS Complete response to nausea was observed in 90.90 %, 60.60 % and 54.54 % in acute, delayed and overall period respectively. Complete response to vomiting was observed in 96.96 %, 69.69 % and 66.66 % in acute, delayed and overall period respectively. Complete response to Grade-2 (or above) nausea was observed in 96.96 %, 93.93 % and 90.90 % in acute, delayed and overall period, respectively. Daytime Grade -3 somnolence which was seen in 2/33 patients (6.06 %) was attributable to olanzapine. Patients receiving olanzapine were more likely to have complete response of nausea and emesis in the early, late, and overall assessment periods especially of higher grade (G2 and G3). CONCLUSIONS The authors concluded that low dose olanzapine 5 mg OD combined with an NK1- receptor antagonist, a 5-HT3–receptor antagonist, and dexamethasone is safe and efficacious in the prevention of CINV in patients receiving HEC. KEYWORDS Olanzapine, Low Dose, CINV, HEC

Netupitant/Palonosetron: A Review in Chemotherapy-Induced Nausea and Vomiting.

Netupitant/palonosetron (NEPA; Akynzeo®), available in oral and intravenous (IV) formulations, is a fixed-dose combination of the neurokinin 1 (NK1) receptor antagonist netupitant (or the prodrug, fosnetupitant, in the IV formulation) and the second-generation serotonin 3 (5-HT3) receptor antagonist palonosetron. Administered as a single dose, (fos)netupitant/palonosetron (in combination with dexamethasone) is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in adults. In clinical trials, (fos)netupitant/palonosetron plus dexamethasone was associated with high complete response rates (no emesis and no rescue medication) in the acute, delayed and overall phases in patients receiving highly or moderately emetogenic chemotherapy, with efficacy maintained over multiple cycles. Further, oral netupitant/palonosetron was found to be superior to palonosetron and non-inferior to aprepitant plus granisetron in preventing CINV in individual trials. Both the oral and IV formulations of the drug combination are well tolerated. The fixed-dose combination is concordant with guideline recommendations and provides a simple and convenient option for prophylaxis against acute and delayed CINV in patients receiving highly or moderately emetogenic chemotherapy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40265-021-01558-2.