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

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

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

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

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

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

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

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

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

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

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

BACKGROUND: Even 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. METHODS: This 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. RESULTS: Seventy-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. CONCLUSIONS: Prolonged use of fosaprepitant can effectively and safely prevent delayed CINV in patients receiving HEC.

Antiemetic use and chemotherapy induced nausea and vomiting related hospitalization costs after highly or moderately emetogenic chemotherapy.

Aim: Despite numerous available antiemetics, chemotherapy induced nausea and vomiting (CINV) still affects many patients, and CINV related hospitalizations and costs often result. Materials & methods: PrecisionQ analyzed its database to evaluate CINV related hospitalizations and costs following antiemetics use including netupitant/fosnetupitant with palonosetron (NEPA), aprepitant/fosaprepitant with ondansetron (APON) or aprepitant/fosaprepitant with palonosetron (APPA) in patients receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy. Results: Database analysis identified 15,583 patient records (807 NEPA, 2023 APON, 12,753 APPA) and mean CINV related hospitalization costs were lower across all patients receiving NEPA (US$301) compared with patients receiving APON ($1006, p < 0.0001) or APPA ($321, p < 0.0001). Conclusion: NEPA is associated with lower CINV related hospitalization costs compared with APON and APPA among patients receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy.

Chemotherapy patients often experience nausea and vomiting that not only has a negative impact on the patient's quality of life but can also result in unplanned hospitalizations with high associated costs. Numerous medications and specific guidelines are available to prevent nausea and vomiting in patients with cancer. Specifically, the combination of two classes of medications (serotonin inhibitors + neurokinin type 1 inhibitors) has been shown to provide the greatest benefit. However, hospitalizations due to nausea and vomiting still occur, and providers require further information to determine the best options for their patients. In this study, the combination of netupitant/fosnetupitant with palonosetron resulted in lower hospitalization costs compared with aprepitant/fosaprepitant with ondansetron or aprepitant/fosaprepitant with palonosetron in chemotherapy patients.

Work loss and activity impairment due to extended nausea and vomiting in patients with breast cancer receiving CINV prophylaxis.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV)'s impact on work loss remains poorly described. We evaluated associations between the duration of CINV episodes, CINV-related work loss (CINV-WL), and CINV-related activity impairment (CINV-AI) in patients with breast cancer receiving highly emetogenic chemotherapy. METHODS: We analyzed data from a prospective CINV prophylaxis trial of netupitant/palonestron and dexamethasone for patients receiving an anthracycline and cyclophosphamide (AC) for breast cancer (NCT0340371). Over the observed CINV duration (0-5 days), we analyzed patient-reported CINV-WL and CINV-AI for the first two chemotherapy cycles. We categorized patients as having either extended (≥ 3 days) or short (1-2 days) CINV duration and quantified its impact on work using the Work Productivity and Activity Impairment Questionnaire (WPAI). RESULTS: Overall, we captured data for 792 cycles in 402 women, including 136 (33.8%) employed patients with 35.3% reporting CINV. Of those with CINV, patients reported CINV-WL in 26 cycles and CINV-AI in 142 cycles. Of those with CINV, 55.3% of extended CINV cycles experienced CINV-WL compared to 16.7% of short CINV cycles (p < 0.001). The relative risk of CINV-WL between extended and short CINV was 3.32 (p < 0.01) for employed patients. The mean difference in CINV-AI scores (higher = worse) between extended and short duration CINV was 5.0 vs. 3.0 (p < 0.001). CONCLUSION: Extended (≥ 3 days) CINV was associated with more than triple the risk of CINV-WL and higher CINV-AI compared with short CINV.

2023 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting.

PURPOSE: This review is an update of the MASCC/ESMO 2015 recommendations for the prophylaxis of acute and delayed nausea and vomiting induced by multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting. METHODS: A systematic literature search was conducted using PubMed from June 1, 2015, through February 1, 2023. RESULTS: We identified 56 references (16 were duplications or invalid), leaving 40 manuscripts for this search. The panel classified level I evidence (three manuscripts) and level II evidence (14 manuscripts). High-dose chemotherapy and stem cell transplant were discussed in four of these manuscripts, and multiple-day chemotherapy treatment in 15. Some manuscripts covered both topics. Additionally, a search for breakthrough nausea and vomiting resulted in 12 "hits." No new relevant studies were identified. CONCLUSIONS: The recommendations for patients receiving high-dose chemotherapy with stem cell transplants and patients undergoing multiple-day cisplatin were updated. For patients receiving high-dose chemotherapy for stem cell transplant, a combination of a 5-HT3 receptor antagonist with dexamethasone and aprepitant is recommended. Olanzapine could be considered part of the antiemetic regimen. Patients receiving multiple-day cisplatin should receive a 5-HT3 receptor antagonist plus dexamethasone plus aprepitant plus olanzapine. For patients experiencing breakthrough nausea and vomiting, the available evidence suggests using a single dose of olanzapine daily for 3 days.

Assessment of the change of antiemetic prophylaxis from double to triple combination in patients with high dose carboplatin chemotherapy.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is one of the adverse events that most affects oncologic patients' quality of life. Carboplatin AUC ≥ 4 belongs to agents with high emetic risk (moderate risk in ASCO guidelines). We aimed to compare the effectiveness of netupitant/palonosetron and dexamethasone triple combination (TC) therapy versus ondansetron and dexamethasone double combination (DC) therapy as antiemetic prophylaxis in patients with carboplatin AUC ≥ 4. As a secondary endpoint, in TC group we evaluated the effectiveness of changing NEPA administration timing from 1 h to 15 min before chemotherapy. METHODS: Open-label prospective study conducted in a tertiary-care hospital in patients receiving carboplatin AUC ≥ 4. CINV was evaluated using MASCC antiemetic tool, in acute (<24 h) and delayed phase (24-120 h). Results were analyzed using χ2 test. RESULTS: Two-hundred four completed questionnaires (CQ) were analyzed (76 in DC and 128 in TC). The proportion of patients who remained emesis-free was superior for TC-treated group compared to DC, either in acute (99.2% vs 92.1%, p = 0.0115) and delayed phase (97.6% vs 90.7%, p = 0.043). Likewise, a higher proportion of TC-treated patients compared to DC remained nausea-free for the first 24 h after treatment (90.6% vs 71%, p = 0.0004) and between 24 and 120 h (82.3% vs 62.7%, p = 0.0025). The change of NEPA administration time showed similar effectiveness in terms of CINV control (81.6% vs 74.5%, p = 0.70). CONCLUSIONS: TC showed superiority in early and delayed CINV control in carboplatin AUC ≥ 4 regimens, with no significant differences among cancer types. Change in NEPA administration timing has beneficial implications; it allows NEPA to be administered at hospitals before chemotherapy session.

Olanzapine within steroid-sparing antiemetic regimen to prevent chemotherapy-induced nausea and vomiting in patients with acute leukemia receiving multi-day intensive chemotherapy.

INTRODUCTION: Olanzapine use for chemotherapy-induced nausea and vomiting (CINV) in hematological malignancies, for multi-day chemotherapy, and with a steroid-sparing antiemetic strategy is poorly understood. This study investigated if olanzapine is associated with improved prevention of CINV when added to a steroid-sparing antiemetic regimen in patients with acute leukemia receiving intensive, moderately emetogenic, multi-day chemotherapy. METHODS: This was a single-center, retrospective cohort study in patients with acute leukemia. Patients who received olanzapine for CINV prevention were compared to those who did not. All patients received a 5-HT3 antagonist. Adult patients receiving moderately emetogenic, multi-day, intensive chemotherapy for acute leukemia were included. Patients were excluded if they received steroids greater than physiological doses during the study period. The primary endpoint was the complete response of CINV (no emesis or rescue antiemetic usage). RESULTS: This study included 58 patients, 12 patients received olanzapine and 46 patients were in the control group. Baseline demographics were similar. In the study population, 89.7% had acute myeloid leukemia, median age was 54 (interquartile range 42-63) years, 34.5% were female, 27.6% had prior CINV. Complete response of CINV was similar between groups, 4 (33.3%) and 15 (32.6%) patients in the olanzapine and control groups, respectively. Safety events were similar between groups. CONCLUSION: Patients with acute leukemia receiving multi-day intensive chemotherapy are at high risk for CINV. The limited data in this study suggests that olanzapine use within a steroid-sparing antiemetic regimen was well tolerated and associated with similar incidence and severity of CINV compared to the control group.

Minimal clinically important difference of the Functional Living Index-Emesis in patients with gynecological malignant tumor: A post hoc analysis of a single-arm study.

AIM: This study aimed to explore the impact of minimum clinically important difference (MCID) of the Functional Living Index-Emesis (FLIE) in patients with gynecologic malignancies. METHOD: This post hoc analysis included patients with gynecological malignant tumors in the Department of Oncology of our hospital between October 2020 and October 2021. RESULTS: A total of 149 patients (aged 50.05 ± 12.24 years) were included. Most of the patients were married (75.8%), lived in the city (60.4%), and had a history of motion sickness (75.8%). The degree of nausea (9.00 [0.00, 16.00] vs. 30.00 [16.00, 48.00], P < 0.001) and vomiting (9.00 [0.00, 16.00] vs. 30.00 [16.00, 48.00], P < 0.001) were significantly improved after treatment. Taking the options in the scale as the subjective anchor, the MCID of FLIE for nausea and vomiting were 28.5 and 29 in anchor-based analysis, respectively. In the distribution-based analysis, the MCID of FLIE for nausea and vomiting were 2.41, 6.04, and 9.66; and 2.31, 5.78, and 9.24 in effect size of 0.2, 0.5, and 0.8, respectively. CONCLUSION: The MCID of FLIE for nausea and vomiting in patients with gynecological malignant tumors was 28.5 and 29 in the anchor-based analysis, with higher specificity, and 6.04 and 5.78 in the distribution-based analysis, with higher sensitivity. The development of the MCID scale might be used to interpret the clinical significance of chemotherapy-induced nausea and vomiting in patients with gynecological malignancies and help to calculate the sample size for future clinical trials.

Evaluating the impact of chemotherapy-induced nausea and vomiting on daily functioning in patients receiving dexamethasone-sparing antiemetic regimens with NEPA (netupitant/palonosetron) in the cisplatin setting: results from a randomized phase 3 study.

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

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.

Prolonged administration of aprepitant improves cisplatin-based chemotherapy-induced nausea and vomiting.

Aims: To determine the antiemetic efficacy of a 6-day aprepitant schedule in patients receiving multiple-day cisplatin. Patients & methods: Patients diagnosed with lung cancer and who were chemotherapy-naive were screened. The patients willing to use aprepitant were randomly divided into two groups: prolonged use of aprepitant (PA; 6-day aprepitant) and standard use of aprepitant (SA; 3-day aprepitant); the patients who rejected aprepitant were recruited into the control group (group C). Primary end points included the safety and the number of days without chemotherapy-induced nausea and vomiting. Results: There was no statistical difference in adverse events among the three groups. The average days without chemotherapy-induced nausea and vomiting of group PA (18.28 ± 3.35) was significantly longer than in groups SA and C. Furthermore, better life function scores were achieved in group PA according to the Functional Living Index - Emesis questionnaire. Conclusion: In this study 6-day aprepitant was safe and more effective than standard 3-day aprepitant in controlling chemotherapy-induced nausea and vomiting due to 3-day cisplatin regimens.

The aim of this study was to determine the effectiveness of a 6-day aprepitant schedule in patients receiving a multiple-day highly emetogenic chemotherapy drug (cisplatin). Aprepitant is an important medication used to prevent chemotherapy-induced nausea and vomiting (CINV). The patients willing to use aprepitant were randomly divided into two groups: prolonged use of aprepitant (PA; 6-day aprepitant) and standard use of aprepitant (SA; 3-day aprepitant). The patients who rejected aprepitant were recruited into the control group. The results showed that cases of CINV in group PA ended more quickly. Group PA also had more days with no vomiting and no nausea than the other two groups. The results of this study propose 6-day aprepitant use as more effective to prevent CINV in patients receiving 3-day cisplatin-based chemotherapy.  Clinical trial registration: ChiCTR-IPR-15005933 (http://www.chictr.org.cn).

Efficacy of the dexamethasone-sparing triplet regimen for preventing cisplatin-induced emesis: a combined analysis.

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

We aimed at further evaluating how well the corticosteroid, dexamethasone (DEX), works as measured in two similar clinical studies of single-day versus multiple-day DEX for the prevention of nausea and vomiting caused by cisplatin, a cell-killing drug, which has high potential of triggering nausea and vomiting. In both studies, cancer patients were randomly assigned to 1-day DEX or multiple-day DEX (3­4 days) in combination with palonosetron (this antagonist attaches to a specific receptor for serotonin without triggering nausea and vomiting), and neurokinin-1 receptor-antagonists (NK-1RAs; they attach to the NK-1 receptor without triggering nausea and vomiting). The combined analysis of the two studies, which includes 242 patients, showed that a single dose of DEX is as effective as multiple-day DEX in terms of the number of patients achieving complete response (defined as no vomiting and no 'as-needed' use of antiemetics) during the 5 days after cisplatin administration. Therefore, administration of single-dose DEX offers comparable antiemetic control to multiple-day DEX when combined with palonosetron and an NK-1RA in patients undergoing single-day cisplatin.

A retrospective study on chemotherapy-induced nausea and vomiting in highly/moderately emetogenic chemotherapy: incidence and prescribing practice.

BACKGROUND: Chemotherapy-induced nausea vomiting (CINV) is a common and significant problem in oncology patients and rated as one of cancer chemotherapy's most distressing side effects. The objectives of this study are to describe the incidence of CINV in highly and moderately emetogenic chemotherapy-treated patients and the prescribing pattern of CINV prophylaxis. METHODS: This retrospective, cross-sectional single-center study randomly collected data on demographics, CINV episodes, and prescribing patterns for adult oncology patients receiving intravenous highly or moderately emetogenic chemotherapy (HEC/MEC) between January and December 2019. RESULTS: A total of 419 randomly selected records of HEC/MEC recipients with 2388 total chemotherapy cycles were included. The mean age was 53.6 ± 12.6 years old. The majority was female (66%), Malay (54.4%), diagnosed with cancer stage IV (47.7%), and with no comorbidities (47%). All patients were prescribed with IV granisetron and dexamethasone before chemotherapy for acute prevention, whereas dexamethasone and metoclopramide were prescribed for delayed prevention. Aprepitant was not routinely prescribed for the prevention of CINV. CINV incidence was 57% in the studied population and 20% in the total cycle. This study found a significant association between CINV incidence with performance status and cisplatin-based chemotherapy (OR = 3.071, CI = 1.515-6.223, p = 0.002; OR = 4.587, CI = 1.739-12.099, p = 0.02, respectively). CONCLUSION: CINV incidence was rather high per patient but relatively low per cycle. Most patients were prescribed with dual regimen antiemetic prophylaxis. IMPACT: This study provides evidence that there was suboptimal use of recommended agents for CINV, and there is a clear need for further improvements in CINV management.

Olanzapine (5 mg) plus standard triple antiemetic therapy for the prevention of multiple-day cisplatin hemotherapy-induced nausea and vomiting: a prospective randomized controlled study.

OBJECTIVE: A prospective randomized controlled trial was conducted to compare 5 mg olanzapine plus standard triple antiemetic therapy for the prevention of nausea and vomiting induced by multiple-day cisplatin chemotherapy. METHODS: Patients who received a 3-day cisplatin-based chemotherapy (25 mg/m2/d) were given either 5 mg olanzapine plus triple therapy with aprepitant, tropisetron, and dexamethasone (quadruple group) or 5 mg olanzapine plus tropisetron and dexamethasone, omitting aprepitant (triplet group). The primary endpoint was the complete response (CR) in the overall phase (OP) (0-120 h) between quadruple group and triplet group. The secondary endpoints were the CR in the acute phase (AP) (0-24 h) and delayed phase (DP) (25-120 h) between two groups. The first time of vomiting was also compared by Kaplan-Meier curves. The impact of chemotherapy-induced nausea and vomiting (CINV) on the quality of life was assessed by the Functional Living Index-Emesis (FLIE). Aprepitant-related adverse effects (AEs) were also recorded. RESULTS: (1) The primary endpoint CR during OP was 76.0% (45/59) vs 67.0% (41/61) between the quadruple group and triplet group (P = 0.271). The secondary endpoint CR during the AP was significantly higher in the quadruple group than in the triplet group, which was 100.0% (59/59) vs 93.0% (57/61) (P = 0.045). The difference of CR during delayed phase between the groups was especially higher in the quadruple group compared to the triplet group (76.0% (45/59) vs 67.0% (41/61) (P = 0.271)). The rate of patients who achieved total protection in the overall phase was also higher in the quadruple group than the triplet group (28.8% (17/59) vs 23.0% (14/61) (P = 0.463)). During the OP, the incidence of no vomiting in the quadruple group and the triplet group was 93.2% (55/59) vs 80.3% (49/61) (P = 0.038), respectively. (2) Kaplan-Meier curves of time to first emesis were obviously longer in the quadruple group compared with the triplet group (P = 0.031). According to FLIE, no impact of CINV on daily life was defined as total score of questionnaire > 108; this study exhibited identical life quality between two groups. (3) The most common aprepitant- or olanzapine-related AEs included sedation, fatigue, and constipation. The occurrences between two groups were identical. CONCLUSION: It may been recommended that 5 mg olanzapine plus tropisetron and dexamethasone, omitting aprepitant triplet regimen as an alternative therapy in prevention CINV induced by multiple-day cisplatin chemotherapy due to the excellent CINV control rate and safety.

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

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

Netupitant/palonosetron without dexamethasone for preventing nausea and vomiting in patients with multiple myeloma receiving high-dose melphalan for autologous stem cell transplantation: a single-center experience.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent adverse events compromising quality of life (QoL) in patients undergoing autologous stem cell transplantation (ASCT). However, CINV prophylaxis is still lacking uniformity for high-dose melphalan (HDM), which is used to condition patients with multiple myeloma (MM). Netupitant/palonosetron (NEPA) is administered with dexamethasone (DEXA) for CINV prevention in several chemotherapy regimens. Our study aims to assess the efficacy of NEPA, without DEXA, in preventing CINV in 106 adult patients with MM receiving HDM and ASCT. All patients had antiemetic prophylaxis with multiple doses of NEPA 1 h before the start of conditioning and after 72 h and 120 h. A complete response (CR) was observed in 99 (93%) patients at 120 h (overall phase). The percentage of patients with complete control was 93%. The CR rate during the acute phase was 94% (n = 100). During the delayed phase, the CR rate was 95% (n = 101). Grade 1 nausea and vomiting were experienced by 82% and 12% of the patients, respectively. Grade 2 nausea was reported in 18% and vomiting in 10% of patients. Our results showed, for the first time, that NEPA, without DEXA, was a well-tolerated and effective antiemetic option for MM patients receiving HDM followed by ASCT.