The efficiency and safety of low-dose apatinib combined with oral vinorelbine in pretreated HER2-negative metastatic breast cancer.

BACKGROUND: Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC. METHODS: This retrospective study included 100 human epidermal growth factor receptor-2 (HER2)-negative mBC patients who received low-dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS. RESULTS: The median follow-up time for this study was 38.1 months. Among 100 patients with HER2-negative mBC, 66 were hormone receptor (HR)-positive/HER2-negative and 34 were triple-negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2-6.8 months) and 23.0 months (95% CI, 19.9-26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR-positive /HER2-negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety-five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3-4. The most common Grades 3-4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%). CONCLUSION: Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC.

Comparison of microwave alone and combined with ethanol ablation for different types of benign mixed thyroid nodules.

OBJECTIVE: To evaluate the efficacy and safety of microwave ablation (MWA) plus ethanol ablation (EA) for different types of benign mixed thyroid nodules. METHODS: A total of 81 patients with 81 benign mixed thyroid nodules were enrolled into the study; 39 were divided to the MWA group and 42 to the combined group (MWA combined with EA). Nodule ablation rate, volume reduction rate (VRR) and surgical complications of all patients were analyzed before and after treatment. RESULTS: The mean ablation rate were 86.49 ± 6.68% and 90.09 ± 5.79% in the microwave and combined groups respectively, and the ablation rate of nodule decreased as the nodule volume increased. For nodules ≥15 ml in volume, the mean ablation rate of the combined group was higher than that of the microwave group (all P < 0.05). The mean VRR at 12 months postoperatively was 89.58 ± 4.32% in the microwave group and 92.92 ± 3.49% in the combined group, showing statistical significantly different between both arms (P = 0.001). The combined group decreased in volume more significantly than the microwave group for nodules with 20-50% or 50-80% cystic proportions or >15 ml in volume (all P < 0.05). The complication rate was 23.08% and 2.38% respectively. CONCLUSION: MWA combined with EA is more effective than MWA for treating mixed thyroid nodules. MWA combined with EA may be the first approach for nodules with >20% cystic proportions or volume >15 ml.

A comparative analysis of antidepressant and anti-suicidal effects of repeated ketamine infusions in elderly and younger adults with depression.

OBJECTIVES: This study aims to investigate the differences in safety and antidepressant effects of multi-infusion ketamine treatment between elderly and young adults with depression. METHODS: The safety, antidepressant, and anti-suicidal effects of multi-infusion ketamine were compared between 19 elderly (≥50 years) and 116 younger (<50 years) adults with depression; all were treated with six ketamine infusions (0.5 mg/kg). Montgomery-Åsberg Depression Rating Scale (MADRS) was used to measure the depressive symptoms, and suicidal ideation was measured with Beck Scale for Suicide Ideation (SSI)-part 1, Hamilton Rating Scale for Depression (HAMD) item 3, and (MADRS) item 10. Dissociative and psychotomimetic symptoms were evaluated based on the Clinician-Administered Dissociative States Scale (CADSS) and the Brief Psychiatric Rating Scale (BPRS)-four items. RESULTS: Multi-Ketamine infusions resulted in a lower (trend) antidepressant response (37.1 % versus 57.8 %) and antidepressant remission (15.8 % versus 47.4 %) in elderly patients with depression compared with younger patients with depression (all ps > 0.05). Interestingly, elderly patients with depression had a higher MADRS score after six ketamine infusions compared with younger patients (p = 0.04). No significant differences in SSI-part 1 scores, HAMD item 3 scores, MADRS item 10 scores, CADSS scores, and BPRS-four items scores were found between the two groups at any assessment point (all ps > 0.05). CONCLUSION: Our study shows that repeated-dose infusions of ketamine may be a feasible treatment strategy in elderly Chinese patients with depression; however, elderly patients with depression may be less responsive to ketamine compared with younger adults with depression.

A single-arm phase II clinical trial of anlotinib combined with chemotherapy for the treatment of metastatic triple-negative breast cancer.

Background: Anlotinib is a novel oral small-molecule tyrosine kinase inhibitor (TKI), which can inhibit angiogenesis. The purpose of this study was to evaluate the efficacy and safety of anlotinib combined with chemotherapy in patients with metastatic triple-negative breast cancer (TNBC). Methods: This phase II clinical trial included 40 patients with metastatic TNBC who had previously received anthracycline and/or taxane treatment. All patients received anlotinib combined with chemotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR) and safety. Results: During May 1, 2019 and April 30, 2022, there were 40 patients enrolled in this study. The median PFS and median OS were 8.8 months (95% confidence interval [CI] 6.5-11.1 months) and 19.0 months (95% CI, 12.1-25.9 months), respectively. The ORR, CBR and DCR were 40.0% (16/40), 85.0% (34/40) and 95.0% (38/40), respectively. Cox univariate and multivariate analyses demonstrated that having more than 3 metastatic sites (p = 0.001; p = 0.020) was an independent and meaningful unfavorable prognostic factor for PFS. 37.5% of patients had grade 3 to 4 treatment-related adverse events (TRAEs). The grade 3 to 4 TRAEs included neutropenia (22.5%), leukopenia (20.0%), secondary hypertension (10.0%), hand-foot syndrome (5.0%), vomiting (5.0%), proteinuria (5.0%) and thrombocytopenia (2.5%). None of the patients withdrew from the study or died due to TRAEs. Conclusion: In this single-arm study, the treatment of metastatic TNBC with anlotinib combined with chemotherapy showed certain efficacy, and its toxicity was acceptable.

Pyrotinib combined with trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2-positive metastatic breast cancer: a single-arm exploratory phase II trial.

PURPOSE: A substantial need for effective and safe treatment options is still unmet for patients with heavily pre-treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Herein, we assessed the efficacy and safety of pyrotinib plus trastuzumab and chemotherapy in patients with heavily treated HER2-positive MBC. METHODS: In this single-arm exploratory phase II trial, patients with HER2-positive MBC previously treated with trastuzumab plus lapatinib or pertuzumab, received pyrotinib plus trastuzumab and chemotherapy. The primary end point was progression-free survival (PFS) in the total population (TP). Secondary end points included PFS in the subgroup with brain metastases (Sub-BrM), confirmed objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), exploration of predictive factors of PFS, and safety. RESULTS: Between November 1, 2018, and March 31, 2021, 40 patients were eligible for this study. The median PFS reached 7.5 months (95% confidence interval [CI] 4.7 to 9.9 months) and 9.4 months (95% CI 6.6 to 12.1 months) in the TP and Sub-BrM, respectively. ORR was 50.5% (20/40). CBR was 75.5% (30/40) and DCR reached 97.5% (39/40). Cox univariate and multivariate analyses demonstrated that liver or/and lung metastases was the significant adverse prognostic factor for PFS (p = 0.018; p = 0.026; respectively). The most frequent grade 3 or 4 treatment-related adverse events were diarrhea, neutropenia and leukopenia. No new safety signals were observed. CONCLUSION: Pyrotinib plus trastuzumab and chemotherapy offered a promising option with manageable safety profile for heavily pre-treated HER2-positive MBC, especially for those without liver or/and lung metastases.

Acute-on-chronic liver failure following eribulin treatment for metastatic breast cancer: a case report.

The efficacy and tolerability of eribulin mesylate, a synthetic halichondrin B analog, in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes have been established. Acute-on-chronic liver failure (ACLF) is a clinical syndrome manifesting as acute and severe hepatic derangement resulting from varied insults in patients with established chronic liver disease or cirrhosis who did not previously receive eribulin. A middle-aged woman diagnosed with MBC and diffuse liver metastases who was pretreated with multi-line chemotherapy received eribulin as eighth-line chemotherapy and presented with hepatic encephalopathy, rapid bilirubin elevation, and significant coagulation dysfunction on day 4 in cycle 1. The patient was diagnosed with ACLF induced by eribulin. Therefore, ACLF may be a lethal and rare adverse event when patients with chronic liver metastases receive eribulin treatment, and clinicians' awareness should be increased for optimal prevention and prompt diagnosis and treatment.

Comparative effectiveness of repeated ketamine infusions in treating anhedonia in bipolar and unipolar depression.

OBJECTIVES: Anhedonia is a common, persistent, and disabling phenomenon in patients with major depressive disorder (MDD) and bipolar depression (BD). This study was conducted to investigate the comparative effectiveness of repeated ketamine infusions in treating anhedonia in Chinese individuals suffering from MDD and BD. METHODS: Ninety-seven individuals suffering from MDD (n = 77) or BD (n = 20) were treated with six intravenous infusions of ketamine (0.5 mg/kg) administered over 40 min. Anhedonia was measured through the Montgomery-Åsberg Depression Rating Scale (MADRS). The antianhedonic response and remission were defined as ≥ 50% and ≥ 75% reduction in MADRS anhedonia subscale score one day after the sixth infusion, respectively. RESULTS: Anti-anhedonic response and remission rates after the sixth ketamine infusion were 48.5% (95% confidence interval =  38.3%-58.6%) and 30.9% (95% confidence interval = 21.6%-40.3%), respectively. When compared to baseline, a significant reduction in the MADRS anhedonia subscale score was observed at 4 h after the first infusion and was maintained with repeated infusions at any time point (all Ps < 0.05). The anti-anhedonic effect of ketamine did not differ between the MDD and BD groups. CONCLUSION: This preliminary study found that repeated ketamine infusions appeared to be effective at rapidly ameliorating anhedonia, with similar efficacy in MDD and BD.

Plasma BDNF concentrations and the antidepressant effects of six ketamine infusions in unipolar and bipolar depression.

OBJECTIVES: Accumulating evidence has implicated that brain derived neurotrophic factor (BDNF) is thought to be involved in the pathophysiology of depression, but its correlation with ketamine's antidepressant efficacy focusing on Chinese individuals with depression is not known. This study was aim to determine the correlation of plasma BDNF (pBDNF) concentrations and ketamine's antidepressant efficacy. METHODS: Ninety-four individuals with depression received six intravenous infusions ketamine (0.5 mg/kg). Remission and response were defined as Montgomery-Asberg Depression Rating Scale (MADRS) scores less than 10 and a reduction of 50% or more in MADRS scores, respectively. Plasma was collected at baseline and at 24 h and 2 weeks after completing six ketamine infusions (baseline, 13 d and 26 d). RESULTS: A significant improvement in MADRS scores and pBDNF concentrations was found after completing six ketamine infusions compared to baseline (all ps < 0.05). Higher baseline pBDNF concentrations were found in ketamine responders/remitters (11.0 ± 6.2/10.1 ± 5.8 ng/ml) than nonresponders/nonremitters (8.0 ± 5.5/9.2 ± 6.4 ng/ml) (all ps < 0.05). Baseline pBDNF concentrations were correlated with MADRS scores at 13 d (t =  - 2.011, p = 0.047) or 26 d (t =  - 2.398, p = 0.019) in depressed patients (all ps < 0.05). Subgroup analyses found similar results in individuals suffering from treatment refractory depression. CONCLUSION: This preliminary study suggests that baseline pBDNF concentrations appeared to be correlated with ketamine's antidepressant efficacy in Chinese patients with depression.