Low Dose Olanzapine in the Prevention and Treatment of Carboplatin Induced Nausea and Vomiting: A Prospective Clinical Randomized Controlled Trial.

OBJECTIVE: This study aimed to determine the effectiveness and safety of 5 mg olanzapine (OLZ) in preventing vomiting and nausea caused by carboplatin chemotherapy. METHODS: All patients with malignant tumors (n = 113) who underwent Carboplatin (AUC ≥ 5) treatment were randomly categorized into two groups: the standard group (n = 57) and the OLZ regimen (n = 56). The major endpoints of the trial were the TC (total control) between two groups during the OP (Overall phase, 0-120 hours), DP (delayed phase, 25-120 hours), and AP (acute phase, 0-24 hours). The secondary endpoints were the CR (complete response) and TP (total protection) during AP, OP, and DP. The time of first vomiting was compared between the two groups using Kaplan-Meier curves. The impact of CINV on the quality of life was assessed by the Functional Living Index-Emesis (FLIE). OLZ-related side effects were also recorded. RESULTS: (1) The primary endpoint TC rates were more favorable in the OLZ regimen group than in the standard group during the AP 87.50% (49/56) vs. 63.15% (36/57) P = 0.003, OP 62.50% (35/56) vs. 31.57% (18/57) P = 0.001, and DP 64.28% (36/56) vs. 33.33% (19/57) P = 0.001. (2) The secondary endpoints TP were 82.14% (46/56) vs. 63.15% (36/57), P = 0.024, 83.92% (47/56) vs. 63.15% (36/57). P = 0.012 during the DP and OP. There was no statistical significance during AP between the two groups. The CR rates were not statistically different between the two groups during the three periods, P > 0.05; (3) The first vomiting time in the OLZ group was delayed compared with the standard group (P = 0.248). The effect on life quality (score ≥ 108) assessed by FLIE was 62.50% vs. 43.48% between the two groups, P < 0.05. The primary side effects of OLZ are fatigue (85%) and somnolence (75%). The primary side effects of the standard group are fatigue (77%) and loss of appetite (85%). CONCLUSION: The 5 mg OLZ-based triple antiemetic regimen is effective and safe in preventing vomiting and nausea induced by Carboplatin.

Association between Body Composition and Peripheral Neurotoxicity in Cancer Patients from North China Taking Nab-Paclitaxel.

Determine the association of lean body mass (LBM) on the incidence and severity of peripheral neurotoxicity in cancer patients who received nab-paclitaxel alone or combined with cisplatin or carboplatin. This prospective clinical study examined 32 cancer patients classified into a sarcopenia or non-sarcopenia group according to the Asian L3 vertebra skeletal muscle index (L3-SMI) at Ordos Central Hospital (China) from December 2020-2021, to compare the incidence and severity of neurotoxicity and analizing the relationship between nab-paclitaxel dose per kg LBM and neurotoxicity. There were 18 patients (56.25%) in the sarcopenia group and 14 (43.75%) in the non-sarcopenia group. The incidences of peripheral and severe neurotoxicity were higher in the sarcopenia group (both P < 0.05). Patients in three different body surface area (BSA) groups received the same nab-paclitaxel dose (260 mg/m2 BSA). However, when patients were divided into three groups according to LBM, they received different doses (low-LBM: 15.18 mg/kg LBM, middle-LBM: 12.82 mg/kg LBM, and high-LBM: 11.14 mg/kg LBM). The incidence of grade-C or higher neurotoxicity of these three groups was 61.54% (8/13), 20.00% (1/5), and 11.11% (1/9). Sarcopenia and a higher dose of nab-paclitaxel per kg LBM were associated with peripheral and severe neurotoxicity. Chemotherapy dosing based on body composition may reduce neurotoxicity in patients receiving nab-paclitaxel.Registration number of Clinical Trial: ChiCTR2000040918.

A Comparison of the Efficacy of 5 mg Olanzapine and Aprepitant in the Prevention of Multiple-Day Cisplatin Chemotherapy-Induced Nausea and Vomiting.

Objective: The significance of this article is to talk about aprepitant and olanzapine 5 mg, compare them, and deeply explore the safety or effectiveness during the whole process of multiple-day cisplatin chemotherapy-induced vomiting and nausea. Methods: This trial was randomized and prospective. It is needed to receive cisplatin chemotherapy (25 mg/m2/d) for three days. Its patients would need to choose to use 5 mg olanzapine or aprepitant for this treatment, combined with 5-HT3 receptor antagonist plus dexamethasone. The primary endpoints were the total protection (TP) during the acute phase (AP) (0-24 hours), delayed phase (DP) (25-120 hours), and overall phase (OP) (0-120 h) between the two groups. The secondary endpoints were the complete response (CR) and total control (TC) during the three phases. The first time of the whole process is particularly important and needs to be observed vigorously. However, the time of the patient's first vomiting symptom is also compared accurately by using the Kaplan-Meier curve. The functional life index vomiting (FLIE) was used to calculate and carefully evaluate the serious impact of nausea and vomiting (CINV) induced by the whole chemotherapy process on the quality of life. About olanzapine, its related symptoms and other side effects and aprepitant were also recorded. Results: (1) The primary endpoint TP rates of the olanzapine and aprepitant groups were similar; for the AP, they were 94.23% (98/104) vs. 95.45% (98/106) P=0.61(P=0.61); for the DP, they were 54.81% (57/104) vs. 54.72% (58/106) (P=0.99), and for the OP, the values were 53.79% (58/105) and 55.31% (56/104), respectively (P=0.99). The secondary endpoints, the TC rates, and CR rates were also comparable in the three phases (P > 0.05). (2) After research and display, the results showed that there was no significant difference between the two groups when they were used for the first time of vomiting and the FLIE index (P > 0.05). (3) The main olanzapine-related adverse event was drowsiness, while that of aprepitant was constipation. Conclusion: The efficacy of 5 mg olanzapine was similar to that of aprepitant, and it also showed an advantageous economic potency ratio in preventing CINV induced by multiple-day cisplatin chemotherapy with increased sedation side effects.

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.

Transplantation of Human Placenta-Derived Mesenchymal Stem Cells Alleviates Critical Limb Ischemia in Diabetic Nude Rats.

Neovasculogenesis induced by stem cell therapy is an innovative approach to improve critical limb ischemia (CLI) in diabetes. Mesenchymal stem cells (MSCs) are ideal candidates due to their angiogenic and immunomodulatory features. The aim of this study is to determine the therapeutic effects of human placenta-derived MSCs (P-MSCs) on diabetic CLI, with or without exogenous insulin administration, and the underlying mechanism of any effect. A series of in vitro experiments were performed to assess the stemness and vasculogenic activity of P-MSCs. P-MSCs were intramuscularly injected at two different doses with and without the administration of insulin. The efficacy of P-MSC transplantation was evaluated by ischemia damage score, ambulatory score, laser Doppler perfusion image (LDPI), capillary, and vascular density. In vivo imaging was applied to track the implanted P-MSCs. In vivo differentiation and in situ secretion of angiogenic cytokines were determined. In vitro experimental outcomes showed the differentiation potential and potent paracrine effect of P-MSCs. P-MSCs survived in vivo for at least 3 weeks and led to the acceleration of ischemia recovery, due to newly formed capillaries, increased arterioles, and secretion of various proangiogenic factors. P-MSCs participate in angiogenesis and vascularization directly through differentiation and cytokine expression.

The properties research of polymerized human placenta hemoglobin before and after lyophilization.

In this study, lyophilization was applied to polymerized human placenta hemoglobin (PolyPHb) solution. The lyophilization process was carried out with freezing at - 70°C for 5 h and two phases of drying: the first phase of drying was carried out at -35°C-35°C for 16 h and the second phase at 35°C for 8 h. Hemoglobin (Hb) concentration, methemoglobin (MetHb) content, oxygen-carrying capacity, Fe(3+) content, pH, UV spectrum, average molecular weight and its distribution, circular dichroism, SDS-PAGE, P50, crystal osmotic pressure, colloid osmotic pressure, zeta potential, average particle size, and other indicators were measured before and after lyophilization. Residual water content and rehydration time of the lyophilized products were also evaluated. All the indicators of lyophilized samples showed that the physical and biochemical properties of PolyPHb are not markedly changed before and after lyophilization. In this light, lyophilization may be a promising method for the preservation of PolyPHb solution.

An optimal polymerization conditions for poly-human placenta hemoglobin with lower mean molecular weight.

OBJECTIVES: To reduce the mean molecular weight [Formula: see text] and to increase the effective polymerization ratio (REff) of polymerized human placenta hemoglobin (PolyPHb). METHODS: Three factors of GDA-PolyPHb process such as the approach of feeding GDA (FGDA), hemoglobin concentration ([Hb]) and the molar ratio of GDA, and hemoglobin(RGDA:Hb) were investigated. Finally, the expansion experiments were conducted with optimal conditions. RESULTS: The data showed that the HBOCs with the REff of 67.35% and lower [Formula: see text] of 162.70 kDa were prepared by optimal conditions. CONCLUSION: Compared to original process, the optimal process greatly decreased the [Formula: see text] and increased the REff.

[Effects of freeze-drying process on polymerized human placenta hemoglobin].

The present study was aimed to investigate the influence of freeze-drying on the quality of polymerized human placenta hemoglobin (PolyPHb). The PolyPHb solution was freeze-drying under suitable conditions. Hemoglobin concentration, methemoglobin (MetHb) content, UV spectrum, Fe3 content, oxygen-carrying capacity, pH, the average molecular weight and its distribution, circular dichroism, oxygen equilibrium curve and other indicators were measured before and after freeze-drying. The appearance, residual water content, rehydration time of the lyophilized product were also evaluated. The results showed that there was no significant difference on all the indicators measured above, which indicated that freeze-drying process had no effect on the physical and chemical properties of PolyPHb, as well as on its biological activity. Therefore, the properties of PolyPHb were stable during this freeze-drying process and could be preserved after such freeze-drying process.