Standard Antiemetic Therapy Research Articles

A phase II study of ME2136 (Asenapine Maleate) plus standard antiemetic therapy for patients, including diabetic patients, receiving cisplatin-based chemotherapy.

Olanzapine combined with the neurokinin-1 receptor antagonist, palonosetron and dexamethasone is the standard treatment for chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC). However, the use of olanzapine poses challenges in patients with diabetes mellitus (DM) due to the potential risk of hyperglycemia. ME2136, antipsychotic similar to olanzapine, is associated with a lower risk of hyperglycemia. This study investigated the antiemetic efficacy and safety of ME2136 for HEC. This single-arm phase 2 study examined the safety and efficacy of ME2136 5mg for 4days in combination with triplet-combination antiemetic therapy. Two cohorts were established for the safety assessment: DM and non-DM. Eligible patients had malignant tumors and were receiving cisplatin-based chemotherapy for the first time. The primary endpoint was the complete response (CR) rate, defined as the percentage of patients without vomiting and not requiring rescue medications in the delayed phase (24-120h). Between December 2020 and January 2022, 40 patients were enrolled, with 20 in each cohort. All patients were included in the safety analysis and 35 in the efficacy analysis. The CR rate in the delayed phase was 71.4% [60% CI 63.1-78.6%] for all patients, 66.7% in the DM cohort, and 76.5% in the non-DM cohort. No treatment-related adverse events ≥ grade 3, including hyperglycemia, were reported. ME2136, when combined with standard triplet-combination antiemetic therapy, is expected to exert similar antiemetic effects to the standard treatment for CINV due to HEC. Currently, ME2136-02 trial is underway to examine the safety and efficacy of triplet-combination antiemetic therapy and a 5-day treatment with ME2136. This study was registered with the Japan Registry of Clinical Trials (jRCT2041200071) on 10 December 2020. Clinical trial registration: This study was registered with the Japan Registry of Clinical Trials (jRCT2041200071) on 10 December 2020.

Assessing the impact of aprepitant on response to dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP).

Despite evidence demonstrating the effectiveness of aprepitant for chemotherapy-induced nausea and vomiting (CINV), its use in stem cell transplant settings across Canada is not standard. While pharmacokinetic data exists, the clinical significance of cytochrome P450 3A4 (CYP 3A4) inhibition of cyclophosphamide by aprepitant is unclear. Reduced activation of cyclophosphamide may reduce the effectiveness of dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP). To compare response rates to DICEP in patients with Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) in the presence and absence of aprepitant. A retrospective review of patients who received full-dose DICEP for relapsed/refractory HL or DLBCL between June 1995 and September 2018 at the Foothills Medical Centre (FMC) in Calgary, Alberta, Canada was conducted. Descriptive statistics were used to assess response rate, as defined by the 2007 International Working Group response criteria. Of the 218 patients included in this study, 87.6% of patients in the control group and 88.5% of patients in the aprepitant group responded to DICEP (difference 0.025 [95% CI, -0.066 to 0.114], p = 0.827). Univariate analyses for age, sex, type of cancer, stage of cancer, number of prior relapses, and relapse status were not significant. No significant differences were observed for secondary outcomes. Response rates to DICEP in relapsed/refractory HL and DLBCL patients were similar regardless of aprepitant use. Considering these results and the effectiveness of aprepitant in CINV, its addition to standard antiemetic therapy in patients receiving DICEP should be given strong consideration in the transplant setting.

Olanzapine treatment effectively relieves breakthrough chemotherapy-induced nausea and vomiting: a real-world experience

BackgroundOlanzapine treatment prevents chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC). However, its role in the secondary prevention of breakthrough CINV in real-world cancer care should be further evaluated.MethodWe conducted a retrospective study on patients receiving olanzapine to prevent breakthrough CINV refractory to standard antiemetic therapy. The major outcome was improvement in CINV, defined as any downgrade in CINV symptoms, according to the Common Terminology Criteria for Adverse Events. Comprete response was defined as no symptoms in CINV, i.e., Grade 0. These outcomes were compared in the HEC versus non-HEC groups and the standard- (5 or 10 mg/day) versus low- (2.5 mg/day) dose groups. The other outcome measurement was adverse events (AEs).ResultsWe analyzed 127 patients, including 92 women, with a median age of 50 years (range: 19–89 years). Baseline CINV severity was grade 1, 2, and 3 in 18%, 69%, and 13% of the patients, respectively. After prophylaxis with olanzapine at doses of 2.5, 5, or 10 mg/day, improvement was observed in 105 (83%) patients, with a complete response in 42 patients (33%). The improvement and complete remission rates for the HEC (n = 96) and non-HEC (n = 31) groups were 86% and 71% (p = 0.048) versus 38% and 19% (p = 0.062), respectively. The rates for the standard- (n = 98) and low- (n = 29) dose groups were 86% and 82% (p = 0.568) versus 28% and 52% (p = 0.015), respectively. Thirty-four patients (27%) experienced olanzapine-related AEs, mainly somnolence (n = 28). Grade 3 or higher AEs were not observed.ConclusionOur study results support the clinical application of olanzapine for the secondary prevention of breakthrough CINV.

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.

Factors affecting the implementation of guideline-based prophylactic antiemetic therapy for chemotherapy-induced nausea and vomiting in Japan: a protocol for a hospital-based qualitative study

IntroductionChemotherapy-induced nausea and vomiting (CINV) decrease patients’ quality of life and negatively impact treatment outcomes. Although standard prophylactic antiemetic therapy for acute CINV recommended by guidelines is effective, poor guideline...

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

ObjectiveA 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.MethodsPatients 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.ConclusionIt 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.

Olanzapine 5 mg for Nausea and Vomiting in Patients with Nasopharyngeal Carcinoma Receiving Cisplatin-Based Concurrent Chemoradiotherapy.

Purpose To explore the efficacy and safety of adding olanzapine (5 mg or 10 mg) to 5-hydroxytryptamine type 3 receptor antagonists (5-HT3 RA), neurokinin-1 receptor antagonists (NK1 RA), and dexamethasone for nausea and vomiting in patients with nasopharyngeal carcinoma (NPC) receiving cisplatin-based concurrent chemoradiotherapy. Methods Patients receiving olanzapine 5 mg or 10 mg combined with 5-HT3 RA, NK1 RA, and dexamethasone during the cisplatin-based concurrent chemoradiotherapy were included. The primary endpoint was the complete response (CR) (no vomiting) rate, and the secondary endpoint was the incidence of no nausea. Results A total of 150 chemotherapy cycles were administrated for 88 patients (75 in the olanzapine 5 mg group and 75 in the olanzapine 10 mg group). The proportions of CR in the olanzapine 5 mg group were comparable to those in the olanzapine 10 mg group in acute (93.3% vs. 94.7%, P = 0.731), delayed (76% vs. 78.7%, P = 0.697), and overall phase (73.3% vs. 77.3%, P = 0.570). Moreover, no nausea rates were also comparable between the two groups in acute (76% vs. 78.7%, P = 0.697), delayed (54.7% vs. 60%, P = 0.509), and overall period (50.7% vs. 57.3%, P = 0.111). Regarding the adverse effects, the incidence of somnolence in the 10 mg group (58.6%) was significantly higher than that in the 5 mg group (41.3%) (P = 0.034), while constipation (20.0% vs. 24.0%, P = 0.554) and hiccups (9.3% vs. 10.6%, P = 0.785) rates were comparable in two groups. Conclusions Patients receiving olanzapine plus standard antiemetic therapy has excellent antiemetic effect in NPC patients receiving cisplatin-based concurrent chemoradiotherapy, and patients with olanzapine 5 mg have a similar antiemetic effect and lower adverse effects compared with those with olanzapine 10 mg.

Comparison of Efficacy and Safety between Standard Triple Antiemetic Therapy and Additional Olanzapine Therapy for Chemotherapy-induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy: A Meta-analysis of Randomized Controlled Trials

Comparison of Efficacy and Safety between Standard Triple Antiemetic Therapy and Additional Olanzapine Therapy for Chemotherapy-induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy: A Meta-analysis of Randomized Controlled Trials

Efficacy of topical capsaicin for cannabinoid hyperemesis syndrome in a pediatric and adult emergency department.

Cannabinoid hyperemesis syndrome (CHS) is a clinical diagnosis characterized by symptoms of recurrent nausea, vomiting, and severe abdominal pain in the setting of chronic cannabis use. Symptoms of CHS are frequently unresponsive to standard antiemetic therapy. Topical capsaicin applied to the abdomen has been cited as a potential effective agent for CHS however robust evidence is lacking. This was a single-center retrospective cohort study to evaluate the efficacy of topical capsaicin in pediatric and adult patients presenting to the emergency department (ED) with suspected or confirmed CHS. The primary outcome assessed was if utilization of capsaicin for CHS resulted in more patients achieving an "efficacious" result, defined as only requiring ≤1 rescue medication for symptom relief after receiving capsaicin or after administration of the first agent in patients who did not receive capsaicin during their ED course. Secondary outcomes included total ED length of stay, time to discharge after administration of the reference agent (RA), proportion of patients requiring admission, total number of medication doses given for symptom relief, change in pain score and episodes of emesis, and proportion of patients returning to the ED within 24 h for the same complaint. Additional analyses were also performed to explore patient characteristics that may be predictive of capsaicin efficacy. 201 patients were included in the final analysis of which 25 were <21 years old and seen in the pediatric ED. A greater proportion of patients in the capsaicin group achieved the primary outcome of efficacy as compared to patients who did not receive capsaicin (55% vs 21%, p < 0.001, unadjusted OR 1.44 [95% CI 0.586-0.820]). There were no differences in secondary outcomes except for time to discharge after administration of the RA which was shorter in the capsaicin group (3.72 vs 6.11 h, p = 0.001). Significantly more patients in the capsaicin group experienced efficacy compared to patients who did not. Time to discharge after administration of the reference agent was shorter for those who received capsaicin compared to patients who did not. Administration of capsaicin did not influence patients' total number of medications received or total ED length of stay. Future research is needed to determine capsaicin's efficacy when utilized earlier in therapy, ideally upon initial diagnosis of CHS, and before additional adjunct medications are administered.

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

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

Chemotherapy-Induced Nausea and Vomiting in Breast Cancer Patients: A Multicenter Prospective Observational Study

Objective:This study aimed to assess the occurrence of chemotherapy-induced nausea and vomiting (CINV) in acute phase (24 h after chemotherapy) and delayed phase (2–5 days after chemotherapy) after standard antiemetic therapy and to explore the risk factors of CINV in the acute and delayed phases.Methods:This prospective and observational study analyzed the data of 400 breast cancer patients scheduled for chemotherapy in two hospitals. The self-report survey was developed to assess the occurrence of CINV and their associated factors. On day 2 and day 6 of chemotherapy, CINV was evaluated by the Multinational Association of Supportive Care in Cancer Antiemetic Tool (MAT). The incidence of acute and delayed CINV was expressed as frequency and percentage.Results:Among 400 patients, 29.8% and 23.5% experienced acute and delayed CINV, respectively. Logistic regression analysis showed that the risk factors associated with acute CINV included pain/insomnia, history of CINV, and highly emetogenic chemotherapy. The history of motion sickness (MS), history of CINV, number of chemotherapy cycles completed, and the incidence of acute CINV were significant risk factors for delayed CINV (all P < 0.05).Conclusions:The results of this study are helpful for nurses to identify high-risk patients with CINV, formulate effective treatment plans, and reduce the incidence of CINV.

Efficacy of olanzapine combined with the standard triplet antiemetic therapy for cisplatin-based chemotherapy: A sub-analysis of a randomized, double-blind, placebo-controlled trial (J-FORCE).

12098 Background: In a randomized, double-blind, placebo-controlled trial (J-FORCE), we previously reported the efficacy of olanzapine (OLZ) 5 mg plus triplet antiemetic therapy for cisplatin (CDDP)-based chemotherapy-induced nausea and vomiting (CINV) in the delayed phase (24–120 h after CDDP treatment). Here, we report the results of a pre-planned subgroup analysis of this trial (in which risk factors were used as the allocation factors). This analysis was designed to determine which patients benefit more from OLZ. Methods: Subgroup analysis was performed on complete response (CR: no emesis and no rescue medication) in the acute (within 24 h of CDDP treatment) and delayed phase and time to treatment failure (TTF: time from CDDP treatment to the first vomiting or use of rescue medication). Data from 705 patients in the efficacy analysis population (354 in the OLZ group and 351 in the placebo (PLA) group) were analyzed by sex (male/female), age (≥55 years/ &lt; 55 years), and CDDP dose (≥70 mg/m2/ &lt; 70 mg/m2). For CR, we calculated point estimates of differences between groups and 95% confidence intervals and performed a Mantel-Haenszel test. We used the Kaplan-Meier method for the analysis of TTF, and comparisons between groups were made using a log-rank test. Results: Delayed CR (OLZ versus PLA) and risk difference (RD) of delayed CR following OLZ treatment were significantly greater than following PLA in the following subgroups: male (83.1% versus 70.5%, RD 12.6%, p = 0.001), female (70.9% versus 56.4%, RD 14.5%, p = 0.021), age ≥55 years (78.7% versus 67.6%, RD 11.1%, p = 0.003), age &lt; 55 years (81.0% versus 57.4%, RD 23.6%, p = 0.005), and CDDP ≥70 mg/m2 (78.8% versus 65.3%, RD 13.5%, p &lt; 0.001). TTF of all subgroups (male/female, ≥55 years/ &lt; 55 years, and ≥70 mg/m2/ &lt; 70 mg/m2) was significantly longer in the OLZ group than in the PLA group (HR 0.493, p &lt; 0.001; HR 0.612, p = 0.022; HR 0.586, p &lt; 0.001; HR 0.401, p = 0.005; HR 0.546, p &lt; 0.001; HR 0.543, p = 0.031, respectively). Conclusions: Our results suggest a benefit of OLZ 5 mg plus triplet therapy regardless of risk factors for CDDP-based CINV. Clinical trial information: UMIN000024676. [Table: see text]

The efficacy of aprepitant in salvage treatment of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy for patients with gastrointestinal cancer.

To evaluate the efficacy of aprepitant and its effect on the quality of life when added to standard antiemetic therapy as salvage therapy. This is an open-label, noncomparative prospective phase II clinical trial. A total of 224 patients receiving initial moderately emetogenic chemotherapy (MEC) were enrolled. Patients received standard antiemetic treatment (5-hydroxytryptamine (5-HT3) antagonists + dexamethasone) in the first cycle. Patients failing to achieve a complete response (CR) during cycle 1 entered cycle 2 with the addition of aprepitant as salvage treatment. Of the 224 patients eligible for cycle 1, 159 (71.0%, 95% CI 65.0-77.0) had a CR, and 65 patients with a noncomplete response (NCR) proceeded to cycle 2 to receive aprepitant-based salvage therapy. Then, 49 (75.4%, 95% CI 64.6-84.1) of these patients achieved a CR. The Functional Living Index-Emesis (FLIE) questionnaire showed that NCR patients in cycle 1 had an improved quality of life after receiving aprepitant-based salvage therapy in cycle 2 (cycle 1 and 2: 80.3 vs 114.0, P < 0.001). Failing to achieve a CR had a significant impact on the quality of life in both cycle 1 (FLIE score of NCR and CR patients: 80.3 vs 119.7, P < 0.001) and cycle 2 (FLIE score of NCR and CR patients: 88.3 vs 122.4, P < 0.001). The addition of aprepitant as salvage therapy for patients with gastrointestinal cancer is effective and has a positive effect on quality of life.

Intergenerational comparison of 5-HT3RA in the prevention of chemotherapy-induced nausea and vomiting in gastric cancer patients receiving cisplatin-based chemotherapy: an observational study using a Japanese administrative claims database.

In chemotherapy-induced nausea and vomiting (CINV), the superiority of the second-generation 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) over the first-generation 5-HT3RA is shown in the delayed emesis in cycle 1. We evaluate the antiemetic efficacy in real-world clinical practice that has not been sufficiently investigated in clinical trials. We included patients who were diagnosed with gastric cancer between April 2012 and June 2017 from the medical claims databases and were treated with cisplatin (≥ 50mg/m2) and standard antiemetic therapy (5-HT3RA + neurokinin-1 receptor antagonist [NK1RA] + dexamethasone). We compared the second-generation 5-HT3RA (2nd group) and the first-generation 5-HT3RA (1st group) groups to evaluate the additional antiemetic drug as the CINV event. In total, 3798 patients were extracted; 1440 and 2358 patients were included in the 1st and 2nd groups, respectively. The clinical and demographic characteristics did not differ between the groups. In the overall (days 1-6) in cycle 1, 51.7% and 44.3% of patients in the 1st and 2nd groups, respectively, had a CINV event. In the acute phase (days 1-2), 38.7% and 30.2% and in the delayed phase (days 3-6), 35.8% and 32.1% of patients in the 1st and 2nd groups, respectively, had a CINV event. Furthermore, the CINV event trend was the same as in cycles 1 to 5. The proportion of CINV events in the 2nd group was smaller than that in the 1st group at any cycle. These findings may suggest consistent antiemetic efficacy of second-generation 5-HT3RA throughout the cycle.

Pharmacotherapeutic Considerations for Use of Cannabinoids to Relieve Symptoms of Nausea and Vomiting Induced by Chemotherapy.

Patients suffering from malignant diseases receive very often highly emetogenic chemotherapy as part of their treatment.With the aim of assessing the efficacy of cannabinoids in treating chemotherapy-induced nausea and vomiting (CINV), we searched the literature published until April 2020 in Medline/PubMed, Embase, the Cochrane Controlled Trials Register, and in specific web pages. Randomized clinical trials comparing cannabinoids efficacy in managing CINV with that of placebo reported absence of vomit-ing (3 trials, 168 patients) and absence of nausea and vomiting (3 trials, 288 participants). In comparison with patients receiving other antiemetics, patients receiving cannabinoids reported no nausea (5 trials, 258 participants), no vomiting (4 trials, 209 participants), and absence of both (4 trials, 414 patients). Across all trials, cannabinoids were more effective in relieving the symptoms of nausea and vomiting induced by cytotoxic therapy than placebo was and slightly better than conventional antiemetics. A retrospective review com-paring nabilone, dronabinol, delta-9-THC, and delta 8-THC with other antiemetics used to manage CINV in pediatric patients showed that these drugs could also be used as adjuvant antiemetics. Cancer patients on highly emetogenic chemotherapy but with insufficiently effective standard antiemetic therapy can be given cannabis preparations containing similar amounts of tetrahydrocannabinol and can-nabidiol, which should be received in strict compliance with the professional guidelines for the treatment of CINV.

Study protocol for SPARED trial: randomised non-inferiority phase III trial comparing dexamethasone on day 1 with dexamethasone on days 1–4, combined with neurokinin-1 receptor antagonist, palonosetron and olanzapine (5 mg) in patients receiving cisplatin-based chemotherapy

IntroductionDexamethasone (DEX) is administered for multiple days to prevent chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy (HEC); however, its notorious side effects have been widely reported. Although...

A randomized trial of individualized versus standard of care antiemetic therapy for breast cancer patients at high risk for chemotherapy-induced nausea and vomiting

PurposeDespite triple antiemetic therapy use for breast cancer patients receiving emetogenic chemotherapy, nausea remains a clinical challenge. We evaluated adding olanzapine (5 mg) to triple therapy on nausea control in patients at high personal risk of chemotherapy-induced nausea and vomiting (CINV). MethodsThis multi-centre, placebo-controlled, double-blind trial randomized breast cancer patients scheduled to receive neo/adjuvant chemotherapy with anthracycline-cyclophosphamide or platinum-based chemotherapy to olanzapine (5 mg, days 1–4) or placebo. Primary endpoint was frequency of self-reported significant nausea, repeated for all cycles of chemotherapy. Secondary endpoints included: duration of nausea, overall total control of CINV, Health Related Quality of Life (HRQoL) using FLIE questionnaire, use of rescue mediation and treatment-related adverse events. Results218 eligible patients were randomised to placebo (105) or olanzapine (113). From days 0–5 following each cycle of chemotherapy, 41.3% (95%CI: 36.1–46.7%) of patients in the placebo group reported significant nausea compared to 27.7% (95%CI: 23.2–32.4%) in the olanzapine group (p = 0.001). Across all cycles of chemotherapy, patients receiving olanzapine experienced a statistically significant improvement in HRQoL (p < 0.001). Grade 1/2 sedation was the most commonly side effect reported at 40.8% in the placebo group vs. 54.1% with olanzapine (p < 0.001). ConclusionIn patients at high personal risk of CINV, the addition of olanzapine 5 mg daily to standard antiemetic therapy significantly improves the control of nausea, HRQoL, with no unexpected toxicities.

Prophylactic effect of rikkunshito, an herbal medicine, for chemotherapy-induced nausea in thoracic cancer patients receiving carboplatin-based chemotherapy.

Rikkunshito has been shown to improve upper gastrointestinal symptoms and anorexia. The aim of this study was to evaluate whether rikkunshito improves chemotherapy-induced nausea in thoracic cancer patients receiving carboplatin (CBDCA)-based chemotherapy. A retrospective before-and-after comparison study was conducted in patients with thoracic cancer receiving the first cycle of CBDCA-based chemotherapy. Among 61 eligible patients, 34 received standard antiemetic therapy with a combination of 5-hydroxytryptamine-3 receptor antagonist and dexamethasone from September 2012 and June 2013 (standard group), while the other 27 received the standard antiemetic therapy plus oral rikkunshito from July 2013 and December 2014 (rikkunshito group). The rates of no nausea showed no significant difference between the standard and rikkunshito group (Overall phase: 64.7 % for standard group vs 74.1 % for rikkunshito group, p = 0.579). Subgroup analysis indicated that, in female patients, the rates of no nausea in rikkunshito groups was significantly higher than in standard group (overall phase: 44.4 % vs 100 %, p = 0.034). Rikkunshito did not demonstrate an additional prophylactic effect on standard antiemetic therapy for nausea in patients with thoracic cancer receiving CBDCA-based chemotherapy, but showed a prophylactic effect of nausea in female patients.

1764P - A phase III trial evaluating olanzapine 5 mg for the prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin: J-FORCE study

BackgroundOlanzapine (OLZ) 10mg added to standard antiemetic therapy including aprepitant (APR), palonosetron (PALO), and dexamethasone (DEX) has been recommended for the prevention of chemotherapy-induced nausea and vomiting (CINV) caused by cisplatin. Guidelines suggest that OLZ at a dose of 5mg should be taken into consideration in patients at risk of sedation. OLZ 5mg showed an equivalent activity and favorable toxicity to somnolence in several phase II studies. We conducted a randomized, double-blind, placebo-controlled phase III trial to evaluate OLZ 5mg in addition to standard antiemetic therapy for the prevention of CINV. MethodsPatients receiving cisplatin (≥ 50mg/m2) were randomly assigned to either OLZ 5mg or placebo on days 1–4, combined with APR, PALO and DEX. The primary endpoint was complete response (CR), defined as no vomiting and no rescue medications in the delayed phase (24–120h). As the secondary endpoints, frequency of sleepiness during daytime and appetite loss were assessed by patient reported outcome. ResultsA total of 710 patients were enrolled (OLZ 356 and placebo 354). CR in the delayed phase was significantly increased with OLZ than with placebo (79% vs. 66%, P<0.001). CR in the acute (0–24h) and overall (0–120h) phase was also significantly increased with OLZ (95% vs. 89%, P=0.002, and 78% vs. 64%, P<0.001, respectively). Although the proportion of sleepiness during daytime was higher in the OLZ group than the placebo group on day 1 (75% vs. 68%, P=0.002), there was no difference found on days 2–5 between the two groups. The proportion of patients who reported appetite loss was significantly lower in the OLZ group than the placebo group on days 2–5 (P<0.001). ConclusionsOLZ 5mg can be considered a new standard antiemetic therapy in patients receiving cisplatin-based chemotherapy. Sleepiness during daytime due to OLZ 5mg seems to be tolerable and addition of OLZ 5mg to the standard antiemetic therapy may reduce appetite loss. Legal entity responsible for the studyMasakazu Abe. FundingJapan Agency for Medical Research and Development. DisclosureS. Iwasa: Honoraria (self): Taiho pharmaceutical; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self): Ono Pharmaceutical; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Bristol-Myers Squib; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Otsuka; Research grant / Funding (institution): Bayer. N. Yamamoto: Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Research grant / Funding (institution): Taiho Pharmaceutical; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Kyowa Hakko Kirin; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): IQVIA; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Merck Serono. Y. Ohe: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly Japan; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options, An Immediate Family Member : Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Kyorin; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: Celltrion; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bayer; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (institution): Taiho pharmaceutical; Honoraria (self): Kyowa Hakko Kirin; Research grant / Funding (institution): Sumitomo Dainippon Pharma; Research grant / Funding (institution): Ignyta. All other authors have declared no conflicts of interest.

Efficacy and safety of topical capsaicin for cannabinoid hyperemesis syndrome in the emergency department

Introduction: Cannabinoid hyperemesis syndrome (CHS) is a disorder of cyclic and recurrent nausea, vomiting, and abdominal pain associated with high-frequency and extended-duration marijuana use. Standard antiemetic therapy is often ineffective; however, capsaicin, an agonist of transient receptor potential vanilloid 1 (TRPV1), has shown promise in treating CHS.Methods: This retrospective cohort analysis evaluated the safety and efficacy of topical capsaicin for patients presenting with CHS. The primary outcome was to assess if utilization of capsaicin for ED management of CHS decreased ED length of stay (LOS) as compared to a visit without capsaicin. Secondary outcomes included a cost analysis, use of rescue therapies, and adverse events.Results: Forty-three patients met the inclusion criteria within the study period. ED LOS was reduced with capsaicin by a median of 22 minutes (201 vs. 179 min, p = 0.33). Patients received fewer additional medications if capsaicin was utilized (4 vs. 3 doses, p = 0.015), and 67% of visits where capsaicin was utilized required no further treatment prior to discharge. Additionally, opioid usage was less when utilizing capsaicin (166.5 vs. 69 mg OME). Forty-two percent of patients did not have a repeat CHS presentation to the ED after receiving capsaicin for an additional three months after the study period ended. Total medication cost was minimally more expensive (median difference of $3.26) in the capsaicin group. There were no significant adverse events reported with capsaicin.Conclusion: There was no significant difference in ED LOS when capsaicin was utilized for CHS. However, there was a decrease in total medications administered and a reduction in opioid requirements. While medication costs for capsaicin visits were minimally more expensive, the utility of capsaicin as an over-the-counter (OTC) product may empower at home therapy with OTC products, decreasing potentially unnecessary healthcare encounters and costs.