A prospective randomized controlled clinical trial investigating the efficacy of low-dose olanzapine in preventing nausea and vomiting associated with oxaliplatin-based and irinotecan-based chemotherapy.

OBJECTIVE: The aim of this study is to assess the clinical efficacy of a 5 mg dosage of olanzapine in preventing chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC) among female patients diagnosed with gastrointestinal tract tumors. METHODS: Patients undergoing the oxaliplatin/irinotecan chemotherapy regimen were enrolled in this prospective controlled study. The olanzapine group received a 5 mg dosage of olanzapine along with palonosetron and dexamethasone, while the control group received a standard two-combination regimen consisting of dexamethasone and palonosetron. The primary endpoints included the total protection (TP) rates for the entire age group and the subgroup aged 60 years and above. Secondary endpoints encompassed the total protection rates during the acute and delayed phases within the two age brackets, as well as the total control (TC) rates and complete remission (CR) rates across all three phases (total, acute, and delayed). Additionally, the study involved the assessment of quality of life and the collection of adverse events associated with the interventions. RESULTS: 1) Regarding the primary endpoint, the total phase TP rates within both the entire age group and the age group exceeding 60 years demonstrated superiority in the olanzapine group when compared to the control group (66.7% vs 37.25%, P = 0.003; 68.8% vs 44.4%, P = 0.044). 2) In terms of secondary endpoints, the olanzapine group exhibited superior acute phase TP rates in both age brackets when compared to the control group (P < 0.05). The olanzapine group also demonstrated higher delayed-phase TP rates, TC rates across all three phases, and CR rates within the two age brackets, although the differences were not statistically significant (P > 0.05). Furthermore, the quality of life in the olanzapine group surpassed that of the control group for both age brackets (P < 0.05), characterized by enhanced appetite and a higher incidence of drowsiness in the patients treated with olanzapine when compared to those in the control group (P < 0.05). CONCLUSION: Olanzapine can enhance CINV induced by MEC regimen in female patients across all age groups, including the elderly, and therefore improve the quality of life for these patients. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/index.html , identifier: ChiCTR20000368269, 25/08/2020.

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.

Clinical Observation of Gene Polymorphism of Olanzapine or Aprepitant in Prevention of CINV.

OBJECTIVE: The present study aims to investigate the correlation between the gene polymorphisms of the multidrug resistance protein 1 (ABCB1), the intron region of transcriptional factor (GTF2E1) and catechol-O-methyltransferase (COMT), dopamine receptor (DRD2), and the control of chemotherapy-induced nausea and vomiting (CINV) by olanzapine or aprepitant in a Chinese population under a fractionated cisplatin dosing pattern. METHODS: Antiemetic treatment with 5 mg of olanzapine or aprepitant triplet therapy was conducted in 210 patients with malignancies receiving cisplatin multi-day chemotherapy. The general data on the patients were collected with the evaluation of the rate of complete protection (TP), complete remission (CR), complete control (TC), and time to first vomiting, the functional living index-emesis (FLIE) scale, and side effects in the acute and delayed phases. The DNA mass spectrometry detected the gene polymorphisms of ABCB1, GTF2E1, COMT, and DRD2, and the correlation with TP was analyzed. RESULTS: 1) There were no statistically significant differences in the TP, CR, TC, time of first vomiting, and FLIE index at different phases between the 5mg of olanzapine group and the aprepitant group (P > 0.05). 2) The main side effect in the olanzapine group was drowsiness (P = 0.00), and in the aprepitant group was constipation (P = 0.02). 3) The distributions of each genotype were in the Hardy-Weinberg (H-W) equilibrium. Univariate analysis showed that in the olanzapine group, delayed-phase TP was correlated with the ABCB1 rs1045642 non-TT (P = 0.01) genotype. CONCLUSION: The present study revealed that females and the rs1045642TT genotype were independent risk factors for delayed-phase CINV in the northern Chinese population, which provided a scientific basis for subsequent CINV-related analysis of high-risk factors in Chinese patients.

Effectiveness and safety of combined neurokinin-1 antagonist aprepitant treatment for multiple-day anthracycline-induced nausea and vomiting.

OBJECTIVE: To assess the safety and efficacy of combined neurokinin-1 antagonist aprepitant treatment for multiple-day anthracycline chemotherapy-induced nausea and vomiting. METHODS: One hundred patients with breast cancer from department of Medical Oncology of Ordos Central Hospital from June 2015 to February 2018 were selected and randomize subdivided into 2 groups. All cases received anthracycline (30 mg/m2/d for pirarubicin or 45 mg/m2/d for epirubicin) and cyclophosphamide adjuvant chemotherapy, along with either the standard therapy (dexamethasone and tropisetron) or the combined aprepitant therapy (aprepitant plus dexamethasone and tropisetron). The results of the observation between groups were presented by complete response in the overall phase (OP, 0-120 hours), acute phase (AP, 0-24 hours) and delay phase (DP, 25-120 hours). The Kaplan-Meier curves were plotted to exhibit the first time of vomiting, Functional Living Index-Emesis of patients' quality of life, and therapy-related adverse effects (AEs). RESULTS: The complete response of OP, AP, and DP were statistically different between aprepitant group and standard group (80.0% vs 48%, P = 0.001; 92.0% vs 74%, P = 0.017; 80.0% vs 48%, P = 0.001). The aprepitant group held a longer time reaching the first emesis after the relevant treatment than the standard group. The Functional Living Index-Emesis increased significantly in the aprepitant group compared with the standard group (24% vs 8.3%, P = 0.029). Fatigue and constipation were the only AEs of aprepitant, since no significant differences were observed in fatigue between the 2 groups (72% vs 70%, P = 0.826), while the incidence of constipation of aprepitant group was higher than the standard group (48% vs 28%, P = 0.039). CONCLUSION: Combined aprepitant therapy is efficient and safe in the multiple-day anthracycline chemotherapy-induced nausea and vomiting control and is recommended for the clinical use.

Evaluation of a Neurokinin-1 Antagonist in Preventing Multiple-day Cisplatin-induced Nausea and Vomiting.

OBJECTIVE: To perform a prospective non-randomized comparison of the effectiveness and safety of combined neurokinin-1 antagonist aprepitant treatment with the standard multiple-day cisplatin regimen for the prevention of cisplatin-induced nausea and vomiting (CINV). METHODS: Patients being administered 3-day cisplatin-based chemotherapy (25 mg/m2/d) who had never received aprepitant were given either the standard regimen (tropisetron and dexamethasone) or the aprepitant regimen (aprepitant plus tropisetron and dexamethasone). The primary endpoint was the complete response (CR) in the overall phase (OP, 0-120 h) between the combined aprepitant triple regimen group and the standard group. Secondary endpoints were the CR in the acute phase (AP, 0-24 h) and delay phase (DP, 25-120 h) between the two groups. The first time of vomiting was also compared by Kaplan-Meier curves. The impact of CINV on the quality of life was assessed by the Functional Living Index-Emesis (FLIE). Aprepitant-related adverse effects (AEs) were also recorded. RESULTS: A CR was achieved by 80.0% in the aprepitant group compared with 56.0% in the standard group during the OP (P =0.018)as well as during the DP. However, during the AP, the aprepitant and standard therapy groups achieved identical CR rates (98.0%, P =1.000). A longer time to first emesis was documented for the aprepitant group than for the standard group. No effect of CINV on quality of life as assessed by FLIE was reported by 44.7% of aprepitant therapy patients and 24.0% of standard therapy patients (P=0.035). The main aprepitant-related AEs were fatigue and constipation, but there was no significant difference between groups. CONCLUSION: Combined aprepitant therapy is recommended for the prevention of multiple-day CINV because of its improved CINV control rate and safety.