Olanzapine or dexamethasone, with 5-HT3 receptor antagonist and NK-1 receptor antagonist, to prevent nausea and vomiting induced by cisplatin-based doublet chemotherapy: A non-inferiority, prospective, multi-centered, randomized, controlled, phase III clinical trial.

TPS12133 Background: Chemotherapy-induced nausea and vomiting (CINV) is a common side effect of cancer treatments, and dexamethasone offers an advantage over placebo for protection against chemotherapy-induced emesis in both acute and delayed phases. However, its side effects are diverse including moderate to severe insomnia, hyperglycemia, dyspepsia and so on, which are gathering increasing concerns. What’s more, dexamethasone is not applicable to all cancer patients. The incidence of diabetes mellitus varies in different cancer which can reach up to 55.3%, and dexamethasone might not be a proper anti-emesis choice for them. Besides, dexamethasone delivery is always on debating when patients are receiving immunotherapy. However, all anti-emesis regimen recommended in guidelines are dexamethasone based. Alternative anti-emesis regimen are required. Studies have shown that olanzapine plays an important role in treating delayed, refractory, breakthrough nausea and vomiting. Thus, we initiated this prospective, multi-center, phase III study to validate the dexamethasone-free protocol: the non-inferiority role of applying olanzapine to prevent CINV instead of dexamethasone. Methods: This clinical trial started on February 3, 2020 is being conducted in 23 centres. All patients eligible are chemotherapy naïve and plan to receive cisplatin-containing regimen. Based on a 70% complete remission rate of previous study, to demonstrate a non-inferiority margin of 10%, 548 patients are required for two arms with the consideration of 5% of drop out and lost to follow-up (80% power,α = 0.05). Study design: Enrolled patients are randomized 1:1 into 2 arms to receive olanzapine or dexamethasone combined with 5-HT3 receptor antagonist (palonosetron, granisetron or ondansetron) and NK-1 receptor antagonist (aprepitant or fosaprepitant) from the first day of chemotherapy. Olanzapine (5mg) is delivered orally per night from day 1 to day 4. Dexamethasone (12 mg) is given orally or intravenously within 30 minutes before cisplatin administrated on day 1; on day 2-4, the orally or intravenously given dose of dexamethasone is 8 mg. The primary endpoint is complete remission rate of vomiting during the whole observation period (0-120 hours from the starting of first course chemotherapy delivery). The secondary endpoints are complete remission rate of vomiting during 25-120 hours from the starting of first course chemotherapy delivery and no nausea rate during the whole observation period. Besides, side effects will be recorded according protocol. Clinical trial information: NCT04437017.

Analysis of the Correlation Between the Tissue Metabolism of Sodium Alginate Microspheres and the Interventional Therapy of Liver Cancer

To explore the tissue metabolism of sodium alginate microspheres in treating liver cancer using alginate microspheres. Rabbit liver cancer model was established by direct inoculation of liver cancer tissues. Rabbits of experimental group were treated with hepatic arterial embolization (HAE) as follows: sodium alginate microspheres was injected through femoral artery to three targeting sites which was 0.5 cm (proximal group), 2 cm (middle group), and 3.5 cm (distal group) far from the lesion, respectively, to block the tumor’s nutrient supply. Short-term clinical efficacy, 3 month survival rate, 6-month mortality rate, 1-year survival rate, and adverse reactions were used as parameters to analyze the prognosis. The complete remission rates of proximal group, middle group, and distal group was 80%, 40%, and 20%, respectively. The complete remission rate of proximal group was significantly higher than other two groups, and the complete remission rate of middle group was significantly higher than distal group (P < 0.05). In terms of progress, a significant difference was observed between proximal group and distal group (P < 0.01). 3-month and 1-year survival rates were increased along with decrease of distance from injection position to the lesion with a correlation equation of y = −15.567x + 104.47 (R2 = 0.9429) and y = −13.333x + 91.133 (R2 =0.9639). Six-month mortality rate decreased along with the decrease of distance from injection position to the lesion with the correlation equation of y = 15.343x−5.9967 (R2 = 0.9943). The prognosis is correlated with the injection position of alginate microspheres. The closer the injection position to the lesion, the better prognosis.

Sirolimus for patients with connective tissue disease-related refractory thrombocytopenia: a single-arm, open-label clinical trial

Objectives Connective tissue disease-related thrombocytopenia (CTD-TP) is a problematic disorder in clinical practice. Because the first-line therapy of glucocorticoid and/or immunosuppressants is not effective for refractory cases, alternative treatment approaches are urgently needed. The present study investigated the efficacy and safety of sirolimus in refractory CTD-TP patients. Methods This single-centre, single-arm, phase II study enrolled 20 refractory CTD-TP patients between September 2017 and September 2018 (registered on ClinicalTrials.gov: NCT03688191). Oral sirolimus administration was dose-adjusted to maintain a therapeutic range of 6–15 ng/ml for 6 months. The primary endpoints were partial and complete remission rates at 6 months. Results Twelve (60%) patients achieved the primary end point with a 50% complete remission rate after 6 months. Among the 14 SLE patients, the overall response rate was 71.4%, with a complete remission rate of 64.3%. None of the primary Sjögren's syndrome cases responded to sirolimus. There was no significant difference in baseline clinical characteristics or lymphocyte subpopulations between responders and non-responders. No severe side effect was detected during the study. Conclusion Sirolimus is an effective and safe treatment option for refractory CTD-TP patients. Trial registration https://clinicaltrials.gov, NCT03688191.

Rituximab treatment for lupus nephritis: A systematic review

Purpose: We used the Cochrane systematic review to analyze the effectiveness and safety of rituximab for lupus nephritis. Methods: Systematic search was performed among Cochrane clinical controlled trials database, MEDLINE, MEDLINE-IN-Process and Other Non-Indexed Citations, EMBASE, EBSCO CINAHL, CNKI, VIP and Wanfang database from the establishment of the database to February 2016. The effectiveness and safety were evaluated in terms of the complete remission rate, total remission rate, urinary protein, Systemic Lupus Erythematosus Disease Activity Index changes and adverse events rate. Data were analyzed by the Review Manager Software version 5.3. Results: Five RCTs that met the inclusion criteria, including a total of 238 patients, were enrolled in our study. The results showed that the complete remission rate in rituximab group was a significantly higher than that of cyclophosphamide group. The difference between the two groups was statistically significant (OR=2.80, 95%CI(1.08,7.26), P=0.03). But there was no significant difference between the two groups in partial and total remission rate. The complete remission rate, partial remission rate and total remission rate in rituximab treatment group was similar compared with mycophenolate mofetil group and rituximab combined with cyclophosphamide group. The adverse reaction rate was also similar among the groups. Conclusion: The study systematically analyzed the effectiveness and safety of rituximab for lupus nephritis, which suggested that the complete remission rate of rituximab in the treatment of lupus nephritis was a significantly higher than that of cyclophosphamide group, while the effectiveness and safety was of no difference compared with cyclophosphamide and mycophenolate mofetil.

A Multicenter Nonrandom Clinical Study Using Induction Regimen of FLAG-IDA or Dae in Treatment of 101 Children with Newly Diagnosed CBF-AML in South of China: Clinical Responses and the Midterm Report of Survival

OBJECTIVE: Patients with core binding factor (CBF) AML generally have a favorable prognosis, but the appropriate intensity of chemotherapy and number of courses are still key points for further exploration by the different leukemic group. Our prospective multicenter clinical study was designed to use high intensity, 4-courses of chemotherapy (backbone of MRC AML 15 protocol) to treat childhood CBF-AML and to observe the feasibility and effectiveness in China. METHODS: Total of 101 children with CBF-AML from 9 centers of south of China were enrolled on the C-HUANAN Children AML 2015 protocol from 2015.1 to 2018.11, accounting for 30.6% of total AML (non-APL) cases. There were 59 boys and 42 girls, aged between 2- 14 years old. The diagnosis of CBF-AML was established by PCR-based detection of RUNX1-RUNX1T1 and CBFβ-MYH11 fusion gene transcripts or by FISH based detection of t(8;21) and inv(16) aberration, respectively. Nine cases were combined with FTL3-ITD. Eleven cases were combined with ASXL1 mutation, and 23 cases were combined with c-KIT mutation. The induction regimen were non-randomized to DAE group and FLAG-IDA group. The induction regimen of DAE group including coures 1 (DAE 3+5+10), course 2 (DAE 3+5+8) . The induction regimen of FLAG-IDA including two courses of FLAG-IDA. Consolidation treatment was same and consisted of 2 courses: 1.HAE or MACE; 2.MidAC. Follow-up observation was then started after 4 courses of treatment. All of patients were followed-up to 06/30/2019, median follow-up time was 25 months. RESULTS: The overall complete remission rate was 93.1% after two courses of induction, 93.8% in the DAE group and 92.8% in the FLAG-IDA group. There was no statistical difference between the two groups. The MRD negative rate (<0.1%) detected by the flow cytometry after first course was 57/87 (65.5%) and 67/77 (87.0%) after second course respectively. The RUNX1-RUNX1T1 or CBFβ-MYH11 gene negative rate was 28/60 (46.7%) and 25/43 (58.1%) after first course and second course of treatment respectively .The overall survival rate (OS) was 83.2%, and the leukemia-free survival rate was 81.1%.Among them, the OS and LFS of the DAE group were 76.4% and 73.2%, respectively, and the OS and LFS of the FLAG-IDA group were 86.3% and 84.6%, respectively( P= 0.331 and 0.241).The OS and LFS of the RUNX1-RUNX1T1 group were 81.8% and 79.2%, respectively.The OS and LFS of the CBFβ/MYH11 group were both 88.9%( P= 0.542 and 0.403). The OS and LFS in CBF-AML with FLT3-ITD positive were both 62.2%. The OS and LFS in CBF-AML without FLT3-ITD were 85.3% and 82.9%, respectively (P=0.045 and 0.081),there was significantly inferior OS in CBF-AML with FLT3-ITD subgroup. Among them, the OS was 60.0% and 85.9% in RUNX1-RUNX1T1 with or without FLT3-ITD group respectively( P=0.041), there was significantly inferior OS in RUNX1-RUNX1T1 with FLT3-ITD subgroup. There were no significant differences in OS and LFS between the CBF with or without C-kit and ASXL1 genes. The overall relapse was 10.9%, and treatment related mortality was 6.9%. Conclusion: The childhood CBF-AML accounted for 30.6% of children's newly diagnosed AML in the South China Children's AML Group. The complete remission rate reached to 93.1% by using 2 courses of intensive induction regimen of DAE or FLAG-IDA. Only 2 courses of consolidation chemotherapy were administered. Two years OS and LFS were higher than 80%.There were significant difference in OS of CBF-AML with FLT3-ITD, and RUNX1-RUNX1T1 AML with FLT3-ITD. There were no significant differences in that of LFS. The overall LFS was close to the outcome of the MRC AML 15 protocol, but there was a gap in OS. The main reason was that the most of relapsed patients abandoned treatment. On other hand the treatment related mortality need to be further reduced. Figure Disclosures No relevant conflicts of interest to declare.

Sodium Alginate Microspheres Tissue Metabolism and Correlation Between Interventional Treatment of Liver Cancer Using Alginate Microspheres and Prognosis of Liver Cancer

To explore the effect of tissue metabolism of sodium alginate microspheres on liver cancer and the correlation between interventional treatment of liver cancer using alginate microspheres and prognosis of liver cancer in rabbits, in order to provide reliable data for human clinical study. Rabbit liver cancer model was established through direct inoculation of liver cancer tissues. Rabbits in experimental group were treated with hepatic arterial embolization (HAE) as follows: sodium alginate microspheres was injected through femoral artery to three sites which was 0.5 cm (proximal), 2 cm (middle), and 3.5 cm (distal) far from the lesion, respectively to block the tumor's nutrient supply. Short-term clinical efficacy, 3 month survival rate, 6-month mortality rate, 1-year survival rate, and adverse reactions were measured. The complete remission rates of proximal group, middle group, and distal group was 80%, 40%, and 20%, respectively. The complete remission rate of proximal group was significantly higher than that of middle group or distal group, with significantly higher complete remission rate of middle group compared with distal group (P < 0.05). In terms of progress, a significant difference was seen between proximal group and distal group (P < 0.01). 3-month and 1-year survival rates were increased along with the decrease of distance from injection position to the lesion with the correlation equation of y = –15.567x + 104.47 (R2 = 0.9429) and y = –13.333x + 91.133 (R2 = 0.9639). Six-month mortality rate was decreased along with the decrease of distance from injection position to the lesion with the correlation equation of y = 15.343x – 5.9967 (R2 = 0.9943). The prognosis was correlated with the injection position of alginate microspheres. The closer the injection position to the lesion, the better prognosis.