The efficacy and safety of anlotinib for subsequent line treatment of small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Anlotinib is one of the tyrosine kinase inhibitors that exhibits promising anti-tumor effect in several cancers. However, the efficacy and safety of anlotinib in pre-treated small cell lung cancer (SCLC) is not well determined. Herein, we performed this meta-analysis to summarize the effectiveness and safety of anlotinib in the treatment of pre-treated SCLC. METHODS: The databases, such as PubMed and Embase, were searched to identify eligible studies. Clinical studies reporting the efficacy and safety of anlotinib in the treatment of patients with pre-treated SCLC were included. The main endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and adverse events. The Review Manager 5.4 and STATA 14 statistical software were used to perform the meta-analysis. RESULTS: A total of 13 studies were included, involving 779 patients with SCLC. The ORR and DCR for the anlotinib group were 0.21 (95%CI: 0.12- 0.31; p < 0.01) and 0.76 (95%CI: 0.69- 0.83; p < 0.01), respectively. The summarized PFS and OS for the anlotinib group were 3.46 (95%CI: 2.68-4.24), and 6.86 (95%CI: 5.79-7.93) months, respectively. Compared with control group, the PFS in the anlotinib group was significantly longer standard mean difference(SMD)=0.76, 95%CI: 0.11, 1.41; p = 0.02). In terms of safety, the most common grade 3 or higher adverse events in the anlotinib group were hypertension (9%; 95%CI: 6%-13%), hand-foot syndrome (6%; 95%CI: 2%-9%), and fatigue (4%; 95%CI: 2%-7%). CONCLUSIONS: Anlotinib may be associated with favorable efficacy outcomes in pre-treated SCLC patients with acceptable safety.

Impact of VKORC1, CYP2C9, CYP1A2, UGT1A1, and GGCX polymorphisms on warfarin maintenance dose: Exploring a new algorithm in South Chinese patients accept mechanical heart valve replacement.

BACKGROUND: Warfarin is the most recommended oral anticoagulant after artificial mechanical valve replacement therapy. However, the narrow therapeutic window and varying safety and efficacy in individuals make dose determination difficult. It may cause adverse events such as hemorrhage or thromboembolism. Therefore, advanced algorithms are urgently required for the use of warfarin. OBJECTIVE: To establish a warfarin dose model for patients after prosthetic mechanical valve replacement in southern China in combination with clinical and genetic variables, and to improve the accuracy and ideal prediction percentage of the model. METHODS: Clinical data of 476 patients were tracked and recorded in detail. The gene polymorphisms of VKORC1 (rs9923231, rs9934438, rs7196161, and rs7294), CYP2C9 (rs1057910), CYP1A2 (rs2069514), GGCX (rs699664), and UGT1A1 (rs887829) were determined using Sanger sequencing. Multiple linear regressions were used to analyze the gene polymorphisms and the contribution of clinical data variables; the variables that caused multicollinearity were screened stepwise and excluded to establish an algorithm model for predicting the daily maintenance dose of warfarin. The ideal predicted percentage was used to test clinical effectiveness. RESULTS: A total of 395 patients were included. Univariate linear regression analysis suggested that CYP1A2 (rs2069514) and UGT1A1 (rs887829) were not associated with the daily maintenance dose of warfarin. The new algorithm model established based on multiple linear regression was as follows: Y = 1.081 - 0.011 (age) + 1.532 (body surface area)-0.807 (rs9923231 AA) + 1.788 (rs9923231 GG) + 0.530 (rs1057910 AA)-1.061 (rs1057910 AG)-0.321 (rs699664 AA). The model accounted for 61.7% of individualized medication differences, with an ideal prediction percentage of 69%. CONCLUSION: GGCX (rs699664) may be a potential predictor of warfarin dose, and our newly established model is expected to guide the individualized use of warfarin in clinical practice in southern China.

Endostar down-regulates HIF-1 and VEGF expression and enhances the radioresponse to human lung adenocarcinoma cancer cells.

To study the effect of endostar on the expression of hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF) and radiosensitization, the changes of A549 cells treated by endostar, radiotherapy and radiotherapy plus endostar were checked by flow cytometry (FCM), methyl thiazolyl tetrazolium (MTT), hoechst staining, and enzyme linked immunosorbent assay (ELISA). The results showed that endostar could block cell periods of A549 and stopped the cell cycle at G2/M and S periods. Cell growth inhibiting and apoptotic rate in the combination group were higher than those in other groups. Meanwhile, the levels of HIF-1 and VEGF expression in the combination group were lower than those of other groups. It suggested that endostar significantly sensitizes the function of radiation in A549 cells by arresting the cell cycle at stage of G2/M and S, increasing the cell growth inhibiting and the apoptotic rate, down-regulating the expression of HIF-1 and VEGF.

Endostar combined with chemotherapy versus chemotherapy alone for advanced NSCLCs: a meta-analysis.

BACKGROUND: Use of recombinant human endostatin combined with conventional cytotoxic therapy to treat tumors has been growing because of evidence of increased efficacy. However, whether antiangiogenic therapy combined with chemotherapy really benefits patients with advanced non-small cell lung cancers (NSCLCs) remains unclear. OBJECTIVES: This study was conducted to evaluate the clinical efficacy and safety of rh-endostatin (Endostar) combined with chemotherapy in the treatment of NSCLC patients. METHODS: We selected data from the Cochrane Library, EMBASE, Medline, SCI,CBM, CNKI, to obtain all clinical controlled trials, including the addition of endostar to chemotherapy in advanced NSCLC patients. Fifteen trials with 1335 patients were included according to the inclusion criteria. All were randomized controlled trials, and two trials were adequate in reporting randomization. Seventeen trials did not mention the blinding methods. RESULTS: Meta-analysis indicated that the NPE arm (Vinorelbine+cisplatin+Endostar) had a different response rate compared with NP(Vinorelbine+cisplatin) arm (OR2.16, 95%CI 1.57 to 2.99). The incidences of severe leukopenia (OR0.94, 95%CI 0.66 to 1.32) and severe thrombocytopenia (OR 1.00, 95%CI 0.64 to 1.57) and nausea and vomiting (OR 0.85, 95%CI 0.61 to 1.20) were similar in the two arms. The NPE plus radiotherapy (RT) arm had a similar response rate compared with NP plus RT arm (OR 2.39, 95%CI 0.99 to 5.79), as were the incidences of leukopenia (OR0.83, 95%CI 0.35 to 1.94), thrombocytopenia (OR 0.78, 95%CI 0.19 to 3.16) and radiation esophagitis (OR 1.00, 95%CI 0.40 to 2.49). CONCLUSIONS: Our results suggested that in the treatment of advanced NSCLC, endostar in combination with platinum-based chemotherapy could improve the response rate without obviously increasing side effects.

Endostar combined with chemotherapy versus chemotherapy alone for advanced NSCLCs: a meta-analysis.

To evaluate the clinical efficacy and safety of rh-endostatin (Endostar) combined with chemotherapy in the treatment of patients with non-small cell lung cancer (NSCLC), we selected data from the Cochrane Library, EMBASE, Medline, SCI, CBM, CNKI, etc to obtain all clinical controlled trials, including the addition of endostar to chemotherapy in advanced NSCLC patients. The quality of included trials was evaluated by two reviewers independently. The software RevMan 5.0 was provided by Cochrane Collaboration and used for meta-analyses. Fifteen trials with 1335 patients were included according to the including criterion. All trials were randomized controlled trials, and two trials were adequate in reporting randomization. Thirteen trials didn't mention the blinding methods. Meta-analysis indicated that the NPE arm (Vinorelbine+ cisplatin+Endostar) had a different response rate compared with NP(Vinorelbine+ cisplatin) arm (OR2.16, 95%CI 1.57 to 2.99). The incidences of severe Leukopenia (OR0.94, 95%CI 0.66 to 1.32) and severe thrombocytopenia (OR 1.00, 95%CI 0.64 to 1.57) and Nausea and vomiting (OR 0.85, 95%CI 0.61 to 1.20) were similar in the NPE arm compared with those in the NP arm. The NPE plus radiotherapy(RT) arm had a similar response rate compared with NP plus RT arm (OR 2.39, 95%CI 0.99 to 5.79). The incidences of Leukopenia (OR0.83, 95%CI 0.35 to 1.94) and thrombocytopenia (OR 0.78, 95%CI 0.19 to 3.16) and radiation esophagitis (OR 1.00, 95%CI 0.40 to 2.49)were similar in the NPE plus RT arm compared with those in the NP plus RT arm. Our results suggest that in the treatment of advanced NSCLCs, Endostar in combination with platinum-based chemotherapy can improve the response rate without obviously increasing side effects.