scholarly journals Association of Hypokalemia Incidence and Better Treatment Response in NSCLC Patients: A Meta-Analysis and Systematic Review on Anti-EGFR Targeted Therapy Clinical Trials

2022 ◽  
Vol 11 ◽  
Author(s):  
Jiawei Zhou ◽  
Jianling Bai ◽  
Yuanping Yue ◽  
Xin Chen ◽  
Theis Lange ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Serum Potassium ◽  
Subgroup Analysis ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Objective Response ◽  
Incidence Rates ◽  
Fixed Effects Model ◽  
Term Survival

BackgroundThis meta-analysis was designed to explore the relationship between the level of serum potassium and the treatment effect of epidermal growth factor receptor (EGFR) antagonist in advanced non-small cell lung cancer (aNSCLC).MethodsWe searched phase II/III prospective clinical trials on treatment with EGFR antagonists for aNSCLC patients. The objective response rate (ORR) and/or the disease control rate (DCR) and the incidence of hypokalemia of high grade (equal to or greater than grade 3) were summarized from all eligible trials. Heterogeneity, which was evaluated by Cochran’s Q-test and the I2 statistics, was used to determine whether a random effects model or a fixed effects model will be used to calculate pooled proportions. Subgroup analysis was performed on different interventions, line types, phases, and drug numbers.ResultsFrom 666 potentially relevant articles, 36 clinical trials with a total of 9,761 participants were included in this meta-analysis. The pooled ORR was 16.25% (95%CI = 12.45–21.19) when the incidence of hypokalemia was 0%–5%, and it increased to 34.58% (95%CI = 24.09–45.07) when the incidence of hypokalemia was greater than 5%. The pooled DCR were 56.03% (95%CI = 45.03–67.03) and 64.38% (95%CI = 48.60–80.17) when the incidence rates of hypokalemia were 0%–5% and greater than 5%, respectively. The results of the subgroup analysis were consistent with the results of the whole population, except for not first-line treatment, which may have been confounded by malnutrition or poor quality of life in long-term survival.ConclusionThe efficacy of anti-EGFR targeted therapy was positively associated with the hypokalemia incidence rate. Treatment effects on the different serum potassium strata need to be considered in future clinical trials with targeted therapy.

scholarly journals FOLFOXIRI versus FOLFOX or FOLFIRI with targeted therapy in patients with mutant BRAF metastatic colorectal cancer: A systematic review and meta-analysis

2020 ◽  
pp. 125-132
Author(s):  
M. Yu. Fedyanin ◽  
E. M. Polyanskaya ◽  
H. H.-M. Elsnukaeva ◽  
A. A. Tryakin ◽  
I. A. Pokataev ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Targeted Therapy ◽  
Metastatic Colorectal Cancer ◽  
Subgroup Analysis ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Systemic Review ◽  
Free Survival

Introduction. Based on the subgroup analysis of the TRIBE study FOLFOXIRI with bevacizumab is the recommended option for patients (pts) with mBRAF metastatic colorectal cancer (mCRC) in the 1st line. However, subgroup analysis of other studies showed conflicting results. Therefore, we performed systemic review and meta-analysis to compare efficacy FOLFOXIRI and doublets with targeted therapy in pts with mBRAF mCRC in terms of progression free survival (PFS), objective response rate (ORR) and overall survival (OS).Methods. We performed a search of all prospective randomizes studies in PubMed, ASCO and ESMO congresses for all years before May, 2020, compared FOLFOXIRI plus bevacizumab or anti-EGFR antibodies and FOLFOX or FOLFIRI with targeted agents at the 1st line with information of the BRAF status. Primary outcome was hazard ratio (HR) for PFS and 95% confidence interval (CI); secondary – HR for OS and odds ratio (OD) for ORR. Fixed effects were used for analysis. Meta-analysis was conducted by Review Manager Ver. 5.3.Results. We identified 6 trials (CHARTA, STEAM, TRIBE, TRIBE2, VISNU, METHEP2), which included 158 pts with mBRAF (FOLFOXIRI – 82 (52%) and doublets – 76 (48%). According to results of the meta-analysis there was a tendency for higher ORR in pts with FOLFOXIRI (OR 2.07, 95% CI 0.61–7.06; p = 0.24; I2 = 27%, p for heterogeneity 0.26; 3 trials). However we didn’t find any significant improvement in PFS (HR 0.89, 95% CI 0.64–1.23; p = 0.48; I2 = 0%, p for heterogeneity 0.63; 5 trials) or OS (HR 0.9, 95% CI 0.37–1.19; p = 0.048; I2 = 71%, p for heterogeneity 0.06; 2 trials) in the group of triplet.Conclusions. FOLFOXIRI with targeted therapy did not show significant improvement in the PFS and OS in pts with mBRAF compared with FOLFOX or FOLFIRI with targeted antibodies. A prospective randomized trial is needed to determine the optimal chemotherapy regimen at the 1st line for pts with mBRAF mCRC.

scholarly journals Congenital toxoplasmosis among Iranian neonates: a systematic review and meta-analysis

2019 ◽  
Vol 41 ◽  
pp. e2019021 ◽  
Author(s):  
Shahabeddin Sarvi ◽  
Tooran Nayeri Chegeni ◽  
Mehdi Sharif ◽  
Mahbobeh Montazeri ◽  
Seyed Abdollah Hosseini ◽  
...  
Keyword(s):  
Systematic Review ◽  
Fixed Effects ◽  
English Language ◽  
Meta Analysis ◽  
Congenital Toxoplasmosis ◽  
Incidence Rates ◽  
Health Concern ◽  
Fixed Effects Model ◽  
Persian Language ◽  
Associated Risk Factors

Toxoplasmosis is a serious zoonotic disease that can lead to abortion and congenital disorders and has a widespread global distribution in humans and animals. The objective of this review was to investigate the incidence of toxoplasmosis in Iranian neonates in order to obtain a comprehensive assessment of the overall situation of the disease for use in developing future interventions. Original studies investigating the incidence of Toxoplasma gondii infections in Iranian neonates were systematically searched in a number of English-language and Persian-language electronic databases. The search process resulted in the inclusion of a total of 11 studies in the systematic review, 10 of which were entered into the meta-analysis. The reviewed articles included 2,230 Iranian neonates investigated through January 1, 2018. Based on the retrieved studies, the overall weighted incidence rates of toxoplasmosis in the Iranian neonatal population and neonates with suspected congenital toxoplasmosis were estimated to be 0.64% (95% confidence interval [CI], 0.31 to 1.09) and 4.10% (95% CI, 2.68 to 5.77), respectively, using a fixed-effects model. The findings of the reviewed studies demonstrate that the incidence of toxoplasmosis is high in Iranian neonates. Accordingly, it can be concluded that toxoplasmosis is a serious public health concern that has been ignored by the Ministry of Health. Therefore, it is essential to perform further studies, in addition to implementing screening and detection programs, using standardized methods to estimate the incidence of toxoplasmosis in Iran and to determine its associated risk factors.

Risk of mineralocorticoid excess syndrome with CYP17 inhibitor abiraterone in prostate cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15140-e15140
Author(s):  
Sandy Ann Itwaru ◽  
Arun Gopal ◽  
Omer Bashir ◽  
Joomee Shim ◽  
Xiaolei Zhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Side Effects ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Abiraterone Acetate ◽  
Fixed Effects Model ◽  
Starting Dose ◽  
Grade 3 ◽  
American Society

e15140 Background: CYP17 inhibitor abiraterone acetate has been used for the treatment of patients with metastatic castration-refractory prostate cancer (CRPC). Hypertension, hypokalemia and edema are the major side effects associated with its use, and may be secondary to the excess of mineralocorticoids due to CYP17 inhibition. We performed a systematic review and meta-analysis of published clinical trials to determine the effect of abiraterone on the development of these side effects. Methods: Databases including Pubmed (July, 1966 to July, 2011), Web of Science, and abstracts presented at the American Society of Clinical Oncology meetings from 2008 to 2011 were searched to identify relevant studies. Eligible studies were prospective clinical trials of patients with prostate cancer receiving abiraterone acetate at the starting dose of 1,000 mg daily with available data on hypertension, hypokalemia and edema. Incidence and relative risk (RR) were calculated using a random-effects or fixed-effects model. Results: A total of seven studies including 1,387 patients with CRPC were selected for analysis. The incidences of all-grade hypertension, hypokalemia, and edema were 13.3% (95% CI: 8.3 to 20.5%), 31.4 % (95% CI: 12.5-59.5%), and 23.4 % (95% CI: 15.6-33.5%) respectively. The incidences of high-grade (grade 3 and above) toxicity were low, with a rate of 3.6% (95% CI: 2.6-5.1%), 2.8 % (95% CI: 0.9 to 8.2%), and 2.1% (95%CI: 1.3-3.2%) for hypertension, hypokalemia, and edema respectively. The risk of hypertension and edema did not change with and without the addition of prednisone (p=0.48 and p=0.40, respectively); however, the risk of hypokalemia was significantly reduced with the addition of prednisone (p = 0.003). In comparison with prednisone alone, the addition of abiraterone did not increase the risk of hypertension (RR 1.22, 95% CI: 0.82 – 1.83, p=0.31), but significantly increased the risk of edema (RR 1.36, 95% CI: 1.10-1.69, p=0.004) and hypokalemia (RR 2.04, 95% CI: 1.42–2.92, p<0.001). Conclusions: There were differential effects of abiraterone on the development of hypertension, hypokalemia, and edema in patients with advanced prostate cancer. Further studies are recommended for optimal treatment.

Risk of fatigue with the targeted therapy for renal cell carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20611-e20611
Author(s):  
Bilal Iqbal ◽  
Shenhong Wu
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Fixed Effects ◽  
Meta Analysis ◽  
High Grade ◽  
Fixed Effects Model ◽  
Randomized Controlled Clinical Trials ◽  
Significant Difference

e20611 Background: Fatigue is one of the major side effects associated with targeted therapeutic agents in the treatment of renal cell carcinoma (RCC), and has negatively affected the optimal use of these drugs. Currently the risk of fatigue has not been well defined. We performed a systematic review and meta-analysis of published randomized controlled clinical trials (RCT) to determine the risk of fatigue in RCC patients treated with targeted therapy. Methods: Databases including PUBMED, Web of Science, and abstracts presented at the American Society of Clinical Oncology meetings up to October, 2012 were searched to identify relevant studies. Eligible studies included prospective RCTs in which a targeted therapy was compared to a control of non-targeted therapy (placebo or interferon) with data available. Incidences and relative risk (RR) were calculated using a random- or fixed-effects model depending on the heterogeneity of the included studies. Results: A total of 5,192 RCC patients (targeted therapy: 3023, control: 2092) from 11 RCTs were selected for analysis. The overall incidences of all-grade and high-grade (ie, grade 3 or above) fatigue were 45.4% (95% CI: 33.0-58.5%) and 7.6% (95% CI: 4.1-13.5%) respectively. The incidences varied significantly among different agents (P<0.001). In comparison with overall controls, the targeted therapy did not significantly increase the risk of all-grade (RR=1.07, 95% CI: 1.0-1.35, p=0.055) or high-grade fatigue (RR= 1.01, 95% CI: 0.68-1.50, P=0.95). However, the targeted therapy significantly increased the risk of all-grade fatigue (RR 1.60, 95% CI: 1.40-2.32; P<0.001), but not high-grade fatigue (RR 1.74, 95% CI: 0.91-3.32; P=0.095) when compared to placebo. There was no significant difference between the targeted therapy and interferon in the risk of all-grade (RR 1.02, 95% CI: 0.90-1.14; P=0.90) or high-grade fatigue (RR 0.86, 95% CI: 0.55-1.36; P=0.53). Conclusions: The targeted therapy may significantly increase the risk of fatigue in a magnitude comparable to interferon.

scholarly journals Association between Thyroid Disease and Severe Coronavirus Disease 2019 (COVID-19) Infection: A Meta-Analysis

2021 ◽  
Author(s):  
Juan Xu ◽  
Yang Li ◽  
Quansong Xia ◽  
Qiong Shi
Keyword(s):  
Confidence Intervals ◽  
Respiratory Infection ◽  
Subgroup Analysis ◽  
Thyroid Disease ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Fixed Effects Model ◽  
Asian Patients ◽  
Seriously Ill ◽  
Review Manager

Background: COVID-19 has resulted in an emerging respiratory infection with a pandemical diffusion since December 2019. We aimed to elucidate whether the presence of thyroid disease might increase the risk of severe COVID-19 infection. Methods: Studies reporting seriously ill in COVID-19 patients with and without thyroid disease combined were searched and 11 relevant studies were subjected to our analysis, and pooled odds ratios (ORs) together with 95% confidence intervals (CIs) were calculated by using STATA and Review Manager Software. Results: In total, 2,995 COVID-19 patients were included in this study. The pooled ORs were calculated using a fixed-effects model according to the heterogeneity. The pooled results revealed that thyroid disease was associated with severe COVID-19 infection in patients (OR = 2.14, 95 % CI: 1.23–3.72, P = 0.007). In the subgroup analysis by type of thyroid disease, hypothyroidism was positively associated with risks of severe COVID-19 infection (OR = 4.78, 95 % CI: 1.59–14.36, P = 0.005), however, no obvious difference was found in the risk regarding the severe COVID-19 infection amongst hyperthyroidism or unclassified thyroid disease. In addition, subgroup analysis stratified by ethnic groups demonstrated that thyroid disease was linked to the risks of severe COVID-19 infection in Asian patients (OR = 2.41, 95 % CI: 1.30–4.48, P = 0.005) rather than non-Asian (OR = 1.31, 95 % CI: 0.35–4.87, P = 0.684). Conclusion: This study indicates a correlation between thyroid disease and severe COVID-19 infection.  

Tolerability of dual checkpoint blockade with nivolumab and ipilimumab: A meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15149-e15149
Author(s):  
Alejandro Ramon Carvajal ◽  
Judy Huang ◽  
Shenhong Wu
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Cancer Patients ◽  
Fixed Effects ◽  
Risk Mitigation ◽  
Meta Analysis ◽  
Checkpoint Blockade ◽  
Discontinuation Rate ◽  
Fixed Effects Model ◽  
Increased Risk

e15149 Background: The dual checkpoint blockade of PD-1 and CTLA-4 with nivolumab and ipilimumab have been used extensively for cancer immunotherapy in clinical practice and trials due to its efficacy. A critical concern is the tolerability of the combination due to the increased risk of severe immune-mediated adverse events. A meta-analysis of clinical trials was performed to assess the treatment tolerability measured as discontinuation due to adverse events. Methods: A search through PubMed as well as abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until December 2019 was performed to identify clinical trials in which the combination of nivolumab and ipilimumab was given to cancer patients. Eligible clinical trials reported a discontinuation rate due to adverse events for the groups of patients receiving nivolumab and ipilimumab. A random or fixed effects model was used to determine summary incidences, relative risks, and 95% confidence intervals. Results: Seven clinical studies which included a total of 3,213 patients (combo: 1746, control: 1467) with various cancers were selected. Overall, the intolerability of nivolumab and ipilimumab measured as the summary incidence of discontinuation due to adverse events was 25.1% (95% CI: 17.8-34.1%). The rate varied significantly with the type of cancer (P < 0.001). The lowest discontinuation rate was in uveal melanoma, with a rate of 11% (95% CI: 2.9-34.2%), and the highest discontinuation rate was in melanoma at 46.3% (95% CI: 36.6-56.4%). In comparison with chemotherapy controls from randomized controls, the intolerability was significantly higher with an relative risk of 2.1 (95% CI: 1.78-2.84) for the combination. Conclusions: There is a substantial risk for intolerability in cancer patients receiving the combination nivolumab and ipilimumab. Further studies are needed for risk mitigation.

Telemedicine intervention–reduced blood pressure in a chronic disease population: A meta-analysis

2020 ◽  
pp. 1357633X2095958
Author(s):  
Wenyan Gao ◽  
Xiaoling Lv ◽  
Xiaogang Xu ◽  
Zhongshan Zhang ◽  
Jing Yan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Subgroup Analysis ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Biomedical Literature ◽  
Cochrane Library ◽  
Fixed Effects Model ◽  
Bias Analysis ◽  
Standard Mean Difference

Introduction Elevated blood pressure (BP) is a leading risk factor for many chronic diseases. Many investigations conducted using telemedicine (TM)-based interventions have the potential to control BP. The purpose of this study was to assess the efficacy of TM-based interventions in reducing BP. Methods Studies were selected from PubMed, PMC, Web of Science, Embase, Google Scholar, Cochrane Library, the Chinese National Knowledge Infrastructure (CNKI) and the Chinese Biomedical Literature Database (CBM) according to the inclusion and exclusion criteria. The mean and standard deviation changes in systolic BP (SBP) and diastolic BP (DBP) were analysed using standard mean difference (SMD) and 95% confidence intervals (CI) with a random-effects model or fixed-effects model to assess the efficiency of controlling BP. Subgroup analysis, influence analysis and publication bias analysis were also conducted. Results Sixteen randomised clinical trials were included in this meta-analysis. A TM-based lifestyle intervention significantly reduced daytime SBP (SMD = −0.18, 95% CI −0.27 to −0.10; p < 0.001) and DBP (SMD = −0.18, 95% CI −0.27 to −0.09; p < 0.001). The results of subgroup analysis indicated that this reduction in BP was reliable when BP interventions lasted for 6 months or longer in populations with cardiovascular disease and hypertension. Moreover, the detection data should be delivered by a device system to ensure accuracy. Discussion A TM-based intervention could reduce daytime SBP and DBP in populations with hypertension and cardiovascular disease. This review provides intuitive evidence of a reduction in BP using TM-based interventions.

scholarly journals The efficacy and safety of combination of PD-1 and CTLA-4 inhibitors: a meta-analysis

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Kongju Wu ◽  
Ming Yi ◽  
Shuang Qin ◽  
Qian Chu ◽  
Xinhua Zheng ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Event ◽  
Targeted Therapy ◽  
Combination Therapy ◽  
Combination Treatment ◽  
Subgroup Analysis ◽  
Response Rate ◽  
Meta Analysis ◽  
Adverse Event Rate ◽  
Efficacy And Safety

Abstract Background Recently, a series of clinical trials showed that combination of anti-programmed cell death-1 (α-PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (α-CTLA-4) could effectively eliminate tumor. However, in comparison with widely adopted mono-immune checkpoint inhibitors, chemotherapy, and targeted therapy, the advantage of combination therapy of α-PD-1 and α-CTLA-4 in response rate and prognosis is controversial especially considering probably increased treatment related adverse event. Thus, we conducted this meta-analysis to explore the efficacy and safety of combination treatment of α-PD-1 and α-CTLA-4. Methods This meta-analysis involved 8 clinical trials. In most trials, the primary endpoint was objective response rate (ORR). Thus we calculated risk ratio (RR) and 95% confidence interval (CI) to compare ORR of patients undergoing different treatment strategies. Moreover, the co-primary endpoints in few trials included progression-free survival and overall survival. Hazard ratio (HR) with 95% CI were employed to weigh the influence of different treatments on prognosis of patients. Subgroup analysis was conducted in patients with high and low expression of PD-L1. Lastly, the safety of combination therapy was evaluated by comparing treatment related adverse events among various treatment groups. Results Our results showed that ORR was significantly higher in patients receiving α-PD-1 plus α-CTLA-4 compared with α-PD-1 (RR 1.31, 95% CI 1.16–1.48) or α-CTLA-4 monotherapy (RR 2.11, 95% CI 1.84–2.43), chemotherapy and targeted therapy (RR 1.41, 95% CI 1.26–1.58). α-PD-1 plus α-CTLA-4 treated patients had a great advantage on monotherapy, chemotherapy and targeted therapy treated patients in PFS. Notably, no significant alteration in total adverse event rate was observed in α-PD-1 plus α-CTLA-4 treated patients. Results of subgroup analysis showed that combination therapy could enhance anti-tumor response in comparison with other treatments, especially for low PD-L1 expression patients undergoing nivolumab treatment (ORR: RR 1.35, 95% CI 1.11–1.65). Conclusion Combination treatment of α-PD-1 and α-CTLA-4 is a feasible strategy with enhanced efficacy and acceptable adverse event. Moreover, for some low PD-L1 expression patients, α-CTLA-4 might decrease the risk of resistance to α-PD-1 and demonstrate the synergistic anti-tumor effect.

Efficacy of Clonidine for Prevention of Perioperative Myocardial Ischemia

2002 ◽  
Vol 96 (2) ◽  
pp. 323-329 ◽  
Author(s):  
Kahoru Nishina ◽  
Katsuya Mikawa ◽  
Takanobu Uesugi ◽  
Hidefumi Obara ◽  
Munetaka Maekawa ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Confidence Interval ◽  
Subgroup Analysis ◽  
Odds Ratio ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Outcome Data ◽  
Fixed Effects Model ◽  
Coronary Arterial Disease ◽  
Manual Search

Background There is a belief that clonidine may be effective in reducing perioperative myocardial ischemic events, although the results of several trials are conflicting. The aim of the current study was to provide a systematic review of randomized controlled trials that tested the efficacy of clonidine in this regard. Methods Data was collected from a MEDLINE search of English-language studies published from 1980 to 1999 and a manual search of bibliographies from retrieved articles. A total of 28 studies were assessed. According to the selection criteria (study design, population, intervention, and outcome) and a quality scoring system, seven studies were finally included in the meta-analysis. After homogeneity was established by Q value, the data were then combined using the fixed-effects model. The pooled odds ratio was calculated. A subgroup analysis based on the types of surgery and administration route was also performed to qualify the results. The results were expressed as odds ratio and 95% confidence interval. Results Heterogeneity of outcome data was negative in the trials. The pooled odds ratio was 0.49 (95% confidence interval 0.34-0.71). In the subgroup analysis, clonidine reduced the incidence of myocardial ischemia in patients undergoing cardiac and noncardiac surgery. Rates of bradycardia were similar in clonidine and placebo groups. Conclusion The meta-analysis suggests that perioperative clonidine reduces cardiac ischemic episodes in patients with known, or at risk of, coronary arterial disease without increasing the incidence of bradycardia. Therefore, these findings strongly justify planning and execution of a definitive study seeking the benefits of clonidine.

A Systematic Review and Meta-Analysis about the Effect of Bisphosphonates on the Risk of Skeletal-Related Event in Men with Prostate Cancer

2020 ◽  
Vol 20 (13) ◽  
pp. 1604-1612
Author(s):  
Congcong Wu ◽  
Hua Jiang ◽  
Jianghua Chen
Keyword(s):  
Prostate Cancer ◽  
Fixed Effects ◽  
Data Extraction ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Control Group ◽  
Fixed Effects Model ◽  
Related Event ◽  
Mineral Density ◽  
Skeletal Related Event

Background: Although the adjuvant therapy of bisphosphonates in prostate cancer is effective in improving bone mineral density, it is still uncertain whether bisphosphonates could decrease the risk of Skeletal- Related Event (SRE) in patients with prostate cancer. We reviewed and analyzed the effect of different types of bisphosphonates on the risk of SRE, defined as pathological fracture, spinal cord compression, radiation therapy to the bone, surgery to bone, hypercalcemia, bone pain, or death as a result of prostate cancer. Methods: A systemic literature search was conducted on PubMed and related bibliographies. The emphasis during data extraction was laid on the Hazard Ratio (HR) and the corresponding 95% Confidence Interval (CI) from every eligible Randomized Controlled Trial (RCT). HR was pooled with the fixed effects model, and preplanned subgroup analyses were performed. Results: 5 RCTs (n = 4651) were included and analyzed finally after screening 51 articles. The meta-analysis of all participants showed no significant decrease in the risk of SRE when adding bisphosphonates to control group (HR = 0.968, 95% CI = 0.874 - 1.072, p = 0.536) with low heterogeneity (I2 = 0.0% (d.f. = 4) p = 0.679). There was no significant improvement on SRE neither in the subgroups with Metastases (M1) or Castration-Sensitive Prostate Cancer (CSPC) (respectively HR = 0.968, 95% CI = 0.874 - 1.072, p = 0.536, I2 = 0.0% (d.f. = 4) p = 0.679; HR = 0.954, 95% CI = 0.837 - 1.088, p = 0.484, I2 = 0.0% (d.f. = 3) p = 0.534). Conclusion: Our study demonstrated that bisphosphonates could not statistically significantly reduce the risk of SRE in patients with prostate cancer, neither in the subgroups with M1 or CSPC.

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