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Efficacy and safety of different molecular targeted agents based on chemotherapy for gastric cancer patients treatment: a network meta-analysis.

ABSTRACT: Increasing numbers of reports have been published to demonstrate that molecular targeted agents are able to improve the efficacy of chemotherapy in gastric cancer. This network meta-analysis aimed to evaluate the efficacy and safety of different molecular targeted agents, which were divided into six groups based on the targets including hepatocyte growth factor receptor (c-MET), vascular endothelial factor and its receptor (VEGF/VEGFR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), mammalian target of rapamycin (mTOR) and tyrosine kinase inhibitor (TKI). These six groups of targeted agents were evaluated for their efficacy outcomes measured by overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). While their safety was measured 7 adverse events, including fatigue, anaemia, vomiting, neutropenia, thrombocytopenia, diarrhea and nausea. A total of 23 articles were included after extensive searching and strict inclusion, HER2 and VEGF(R) turned out to be the two most effective targeted drugs for their outstanding performance in OS and PFS. However, they were associated with severe adverse events, including fatigue, neutropenia and diarrhea. Therefore, they should be used with caution during their application. In conclusion, VEGF(R) and HER2 have the potential to be the optimal target agents for their survival efficacy, while the adverse events associated with them should be paid attention in application.

SUBMITTER: Ren Z

PROVIDER: S-EPMC5564643 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Efficacy and safety of different molecular targeted agents based on chemotherapy for gastric cancer patients treatment: a network meta-analysis.

Ren Zheng Z Sun Jinping J Sun Xinfang X Hou Hongtao H Li Ke K Ge Quanxing Q

Oncotarget 20170701 29

Increasing numbers of reports have been published to demonstrate that molecular targeted agents are able to improve the efficacy of chemotherapy in gastric cancer. This network meta-analysis aimed to evaluate the efficacy and safety of different molecular targeted agents, which were divided into six groups based on the targets including hepatocyte growth factor receptor (c-MET), vascular endothelial factor and its receptor (VEGF/VEGFR), human epidermal growth factor receptor 2 (HER2), epidermal ...[more]

PMID: 28477027

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Project description:BackgroundClinical trials of human epidermal growth factor receptor 2 (HER2)-targeted agents added to standard treatment have been efficacious for HER2-positive (HER2+) advanced breast cancer. To our knowledge, no meta-analysis has evaluated HER2-targeted therapy including trastuzumab emtansine (T-DM1) and pertuzumab for HER2-positive breast caner and ranked the targeted treatments. We performed a network meta-analysis of both direct and indirect comparisons to evaluate the effect of adding HER2-targeted agents to standard treatment and examined side effects.MethodsWe performed a Bayesian-framework network meta-analysis of randomized controlled trials to compare 6 HER2-targeted treatment regimens and 1 naïve standard treatment (NST, without any-targeted drugs) in targeted treatment of HER2+ breast cancer in adults. These treatment regimens were T-DM1, LC (lapatinib), HC (trastuzumab), PEC (pertuzumab), LHC (lapatinib and trastuzumab), and PEHC (pertuzumab and trastuzumab). The main outcomes were overall survival and response rates. We also examined side effects of rash, LVEF (left ventricular ejection fraction), fatigue, and gastrointestinal disorders, and performed subgroup analysis for the different treatment regimens in metastatic or advanced breast cancer.ResultsWe identified 25 articles of 21 trials, with data for 11,276 participants. T-DM1 and PEHC were more efficient drug regimens with regard to overall survival as compared with LHC, LC, HC and PEC. The incidence of treatment-related rash occurs more frequently in the patients who received LC treatment regimen than PEHC and T-DM1 and HC. In subgroup analysis, T-DM1 was associated with increased overall survival as compared with LC and HC. PEHC was associated with increased overall response as compared with LC, HC, and NST.ConclusionsOverall, the regimen of T-DM1 as well as pertuzumab in combination with trastuzumab and docetaxel is efficacious with fewer side effects as compared with other regimens, especially for advanced HER2+ breast cancer.ImpactThis study suggests that both T-DM1 and PEHC therapy are potentially and equally useful treatments for HER2+ breast cancer.

Project description:BackgroundSignificant blood loss is still one of the most frequent complications in spinal surgery, which often necessitates blood transfusion. Massive perioperative blood loss and blood transfusion can create additional risks. Aprotinin, tranexamic acid (TXA), and epsilon-aminocaproic acid (EACA) are antifibrinolytics currently offered as prophylactic agents to reduce surgery-associated blood loss. The aim of this study was to evaluate the efficacy and safety of aprotinin, EACA, and low/high doses of TXA in spinal surgery, and assess the use of which agent is the most optimal intervention using the network meta-analysis (NMA) method.MethodsFive electronic databases were searched, including PubMed, Cochrane Library, ScienceDirect, Embase, and Web of Science, from the inception to March 1, 2018. Trials that were randomized and compared results between TXA, EACA, and placebo were identified. The NMA was conducted with software R 3.3.2 and STATA 14.0.ResultsThirty randomized controlled trial (RCT) studies were analyzed. Aprotinin (standardized mean difference [SMD]=-0.65, 95% credibility intervals [CrI;-1.25, -0.06]), low-dose TXA (SMD = -0.58, 95% CrI [-0.92, -0.25]), and high-dose TXA (SMD = -0.70, 95% CrI [-1.04, -0.36]) were more effective than the respective placebos in reducing intraoperative blood loss. Low-dose TXA (SMD = -1.90, 95% CrI [-3.32, -0.48]) and high-dose TXA (SMD = -2.31, 95% CrI [-3.75, -0.87]) had less postoperative blood loss. Low-dose TXA (SMD = -1.07, 95% CrI [-1.82, -0.31]) and high-dose TXA (SMD = -1.07, 95% CrI [-1.82, -0.31]) significantly reduced total blood loss. However, only high-dose TXA (SMD = -2.07, 95% CrI [-3.26, -0.87]) was more effective in reducing the amount of transfusion, and was significantly superior to low-dose TXA in this regard (SMD = -1.67, 95% CrI [-3.20, -0.13]). Furthermore, aprotinin (odds ratio [OR] = 0.16, 95% CrI [0.05, 0.54]), EACA (OR = 0.46, 95% CrI [0.22, 0.97]) and high dose of TXA (OR = 0.34, 95% CrI [0.19, 0.58]) had a significant reduction in transfusion rates. Antifibrinolytics did not show a significantly increased risk of postoperative thrombosis. Results of ranking probabilities indicated that high-dose TXA had the greatest efficacy and a relatively high safety level.ConclusionsThe antifibrinolytic agents are able to reduce perioperative blood loss and transfusion requirement during spine surgery. And the high-dose TXA administration might be used as the optimal treatment to reduce blood loss and transfusion.

Project description:The aim of our meta-analysis is to assess the efficacy and safety of the target combined chemotherapy for the patients with unresectable advanced or recurrent gastric cancer.In accordance with the standard meta-analysis procedures, the patients included in our study were with unresectable advanced or recurrent gastric cancer and allocated randomly to receive target combined chemotherapy or the traditional chemotherapy. The search was applied to PubMed, EMBASE, Science Citation Index Expanded, Cocran's library (from inception to February 2016). All analyses were performed by STATA 12.0, with the odds ratio, hazard ratio, and 95 % confidence interval as the effect measures.Fourteen studies were included in this meta-analysis. A total of 5067 patients with advanced gastric cancer were divided into two arms: traditional chemotherapy arm and target combined chemotherapy arm. A significant improvement for overall survival (hazard ratio was 0.89, 95 % confidence interval: 0.83-0.95) and overall response rate (odds ratio was 1.44, 95 % confidence interval: 1.15-1.81) was observed, but no significant difference was found for progression-free survival (hazard ratio was 0.89, 95 % confidence interval: 0.77-1.00) in the target combined chemotherapy arm. In subgroup analysis, increasing benefits regarding overall survival and progression-free survival were found in anti epidermal growth factor receptor target drugs for selected patients subgroup and anti vascular endothelial growth factor receptor target drugs for unselected patients subgroup, but not in anti epidermal growth factor receptor target drugs for unselected patients subgroup. Besides, some adverse events were increased in the target combined chemotherapy arm.The target combined chemotherapy represented a better overall survival benefit and treatment efficiency and higher incidence of some grade 3-4 adverse events than the traditional chemotherapy for patients with unresectable advanced or recurrence gastric cancer. The anti vascular endothelial growth factor receptor drugs can improve the efficacy in the whole patients with unresectable advanced or recurrence gastric cancer and the anti epidermal growth factor receptor target drugs can only improve the efficacy in the epidermal growth factor receptor positive patients.

Project description:Background: The efficacy and safety of immunosuppressive monotherapy agents were evaluated for immunoglobulin A nephropathy (IgAN) using a network meta-analysis approach. Methods: Randomized controlled trials (RCTs) published prior to October 1, 2019, using immunosuppressive agents for treating IgAN, were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science databases. Relative risks (RRs) or standard mean differences with 95% confidence intervals (CIs) were estimated using the random-effects model. The primary outcomes were clinical remission, end-stage renal disease (ESRD), and serious adverse events (SAEs). The secondary outcomes were urinary protein excretion and serum creatinine. Results: Twenty-five RCTs with 2,005 participants were deemed eligible. Six medications were evaluated: corticosteroids, mycophenolate mofetil (MMF), tacrolimus (TAC), cyclosporine, leflunomide, and hydroxychloroquine (HCQ). Steroids (RR 1.50, 95% CI 1.17-1.93), MMF (RR 2.05, 95% CI 1.15-3.65), TAC (RR 3.67, 95% CI 1.06-12.63), and HCQ (RR 3.25, 95% CI 1.05-10.09) significantly improved clinical remission rates compared to supportive care alone. Only steroids reduced the risk of ESRD (RR 0.35, 95% CI 0.12-0.98); however, there were significantly more SAEs than in the control group (RR 2.90, 95% CI 1.37-6.13). No significantly different effects in serum creatinine levels were found among the therapies. MMF showed no significant improvement in remission when excluding studies with a follow-up of fewer than 2 years in the sensitivity analysis (RR 1.41, 95% CI 0.40-4.92). The effect of TAC in the decrease of proteinuria was reversed after discontinuing medication for 3 months; the long-term effects of HCQ could not be evaluated due to the short follow-up duration. Conclusion: Corticosteroids might induce remission and increase renal survival in IgAN; however, adverse reactions should be taken into consideration. MMF, TAC, and HCQ might improve the remission of proteinuria when treating IgAN, but showed no superiority compared to steroids, and the long-term effects require further study.

Project description:BACKGROUND:Elemene is a natural compound extracted from Zingiberaceae plants, and is used in various cancer. However, the efficacy and safety elemene combined with chemotherapy in advanced gastric cancer (GC) are lack of systematic assessment. METHODS:we searched the PubMed, EMBASE, Web of Science, Cochrane Library, China Academic Journals (CNKI), Chinese Science and Technology Journals (CQVIP) and Chinese Biomedical Literature databases. Randomized controlled trials (RCTs) comparing elemene plus chemotherapy with chemotherapy alone in participants with advanced GC and reporting at least one of the following outcomes were selected and assessed for inclusion. JADAD scale was used to assess the quality. Data was screened and extracted by two independent investigators. The primary clinical outcome was overall response rate (ORR); the secondary outcomes were quality of life (QOL) and adverse events (AEs). Analysis was performed using Review Manager 5.3. RESULTS:Sixteen RCTs matched the selection criteria, which reported on 969 subjects. Risk ratios (RR) and corresponding 95% confidence intervals (CIs) were pooled for ORR, life quality based on KPS, and risk of AEs. Compared to chemotherapy alone, elemene combined with chemotherapy in the treatment of GC may increase the efficiency of ORR(RR: 1.41; 95% CI: 1.23-1.60; P?<?.0001), improve their life quality based on KPS (RR: 1.84; 95% CI: 1.45-2.34; P?<?.00001), and reduce the adverse reactions, including leukopenia(RR: 0.73; 95% CI: 0.62-0.85; P?<?.00001), neutropenia (RR: 0.75; 95% CI: 0.60-0.95; P?=?.02), anemia (RR: 0.76; 95% CI: 0.60-0.95; P?=?.02), thrombocytopenia (RR: 0.56; 95% CI: 0.43-0.73; P?<?.00001). Nausea and vomiting (RR: 0.84; 95% CI: 0.84-1.07; P?=?.39), diarrhea (RR: 0.69; 95% CI: 0.41-1.15; P?=?.15), neurotoxicity (RR: 0.77; 95% CI: 0.59-1.00; P?=?.05) and hepatic dysfunction (RR: 0.95; 95% CI: 0.58-1.54; P?=?.83) were similar between two groups. CONCLUSIONS:Elemene may have the potential to improve the efficacy and reduce the AEs of chemotherapy for gastric cancer. However, the long-term, high-quality researches with a large sample size in different populations are required.

Dataset Information

Efficacy and safety of different molecular targeted agents based on chemotherapy for gastric cancer patients treatment: a network meta-analysis.

Publications

Efficacy and safety of different molecular targeted agents based on chemotherapy for gastric cancer patients treatment: a network meta-analysis.

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