S-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with depression: An updated systematic review and meta-analysis.

BACKGROUND: Major depressive disorder (MDD) is an intractable disease requiring long-term treatment. S-adenosyl-L-methionine (SAMe), a natural substance, has antidepressant effects, but the exact effect remains unclear. This study examines the evidence concerning the efficacy of SAMe as a monotherapy or in combination with antidepressants. METHODS: The PubMed, EMBASE, and Cochrane electronic databases were searched for meta-analyses of randomized controlled clinical trials (RCTs) until June 30, 2023. We performed a systematic review and meta-analysis of the enrolled trials that met the inclusion criteria, with the aim to compare the effects of SAMe to those of a placebo or active agents, or SAMe combined with other antidepressants in the treatment of MDD. RESULTS: Fourteen trials, with a total of 1522 subjects, were included in this review. The daily dose of SAMe varied from 200 to 3200 mg and the study duration ranged between 2 and 12 weeks. The results of SAMe versus placebo as a monotherapy, SAMe versus imipramine or escitalopram as a monotherapy, and SAMe versus placebo as an adjunctive therapy, showed no significant difference in depression with SAMe compared to the comparison treatment. CONCLUSIONS: SAMe may provide relief of depression symptoms similar to imipramine or escitalopram. However, the results of the comparisons should be interpreted with caution due to the small number of studies and the large range of SAMe doses that were used in the included trials. Therefore, we recommend that patients discuss treatment options with their doctor before taking SAMe.

Phenotype, genotype, and clinical outcome of Taiwanese with congenital nephrotic syndrome.

BACKGROUND/PURPOSE: Congenital nephrotic syndrome (CNS) is one of the important causes of end-stage kidney disease in children. Studies on the genotype, phenotype, and clinical outcome in infants with CNS caused by genetic mutations are scarce. METHODS: We analyzed the genetic background, clinical manifestations, treatment response, and prognosis of pediatric patients with CNS in Taiwan. RESULTS: Fifteen infants with CNS were enrolled, and 11 patients of median age 21 (interquartile range 3∼44) days caused by genetic mutations from 10 unrelated families were included in the study. Of the eleven patients, 9 had extra-renal manifestations including microcephaly, facial dysmorphism, and skeletal anomalies. More than two-thirds of the patients had disease onset before 1 month of age. Diffuse meningeal sclerosis was the most common histological characteristic. Whole exome sequencing followed by direct Sanger sequence revealed mutations in OSGEP (R247Q), WT1 (R366H and R467Q), LAMB2 (Q1209∗ and c. 5432-5451 19 bp deletion), NUP93 (D302V), and LAGE3 (c.188+1G > A). Three of the variants were novel. Corticosteroids and/or immunosuppressants were administered in 2 patients, but both were refractory to treatment. During the mean 3.5 years of follow-up, all but two died of uremia and sepsis. The two survivors reached end-stage kidney disease and required peritoneal dialysis, and one of them underwent uneventful renal transplantation. CONCLUSIONS: The majority of patients with CNS in Taiwan were caused by OSGEP followed by WT1 mutation. R247Q is the hotspot mutation of OSGEP in Taiwan. CNS patients in Taiwan suffer from significant morbidity and mortality.

Efficacy and safety of cyclin-dependent kinase 4/6 inhibitor in patients with advanced breast cancer: A real-world experience.

BACKGROUND: Cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) have been shown to improve progression-free survival (PFS) in patients with metastatic breast cancer (MBC) in randomized control trials. This study aimed to evaluate the efficacy and safety of CDK4/6i in patients with advanced breast cancer (ABC) in a clinical setting. METHODS: Consecutive patients with ABC were treated between October 2019 and March 2023 at Taipei Tzu Chi Hospital, Taiwan. Patients who had received at least one dose of CDK4/6i were included in this retrospective study. The main outcome of this study was efficacy based on the treating physicians' assessments in terms of PFS, and overall survival (OS), as well as the factors associated with patient outcome. The secondary outcome was safety. RESULTS: A total of 85 patients were included in the analysis, with a mean age of 66.8 years. After a median follow-up of 16.1 months, the median PFS was 28.4 months (95% CI: 22.5-33.6) and the median OS could not yet be estimated. The most common adverse events (AE) were fatigue (50.8%), anorexia (45.9%), and leukopenia (44.7%). In multivariable analysis, treatment with CDK4/6i with any grade AE or response to treatment effect (CR/PR) was an independent predictor for longer PFS (hazard ratio [HR] = 0.27, 95% CI: 0.11-0.68; HR = 0.21, 95% CI: 0.06-0.67; p < 0.05). CONCLUSION: CDK4/6i administered in a real-world setting exhibits a similar survival benefit with the clinical trials.

Efficacy and safety of anaplastic lymphoma kinase inhibitors for non-small cell lung cancer: A systematic review and network meta-analysis.

BACKGROUND: To assess the efficacy and safety of anaplastic lymphoma kinase inhibitors (ALKIs) for the treatment of advanced-stage ALK rearrangement-positive non-small cell lung cancer (NSCLC). METHODS: We searched PubMed, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) that included patients with ALK-positive NSCLC receiving ALKIs. The outcomes of the study included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs) of grade ≥3. RESULTS: A total of 12 RCTs consisting of 3169 patients with eight treatment options were included in this study. Our results showed that ALKIs have superior efficacy in OS, PFS, and ORR than chemotherapy or crizotinib (first-generation ALKI). Our study showed that only alectinib has a significant improvement in OS compared to chemotherapy (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.40-0.94). Alectinib appeared to have better OS than crizotinib (HR, 0.66; 95% CI, 0.45-0.95). Ensartinib has a significant PFS advantage over alectinib (HR, 0.62; 95% CI, 0.40-0.96). The surface under the ranking curve indicated that ensartinib (99.0%) was the highest rank regarding PFS. Moreover, both ensartinib and ceritinib showed significantly higher TRAEs of grade ≥3 compared with chemotherapy (risk ratios [RR], 2.74; 95% CI, 1.45-5.18; RR, 1.80; 95% CI, 1.26-2.57, respectively). CONCLUSIONS: These results indicated that alectinib could be associated with the best therapeutic efficacy and well-tolerance AEs in the treatment of ALK-positive NSCLC.

Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Proton pump inhibitors (PPIs) may be associated with gastric cancer, but studies in recent years have proven still inconsistent results. We conducted a systematic review and meta-analysis to investigate the association between PPI use and gastric cancer. METHODS: Pubmed, EMBASE, and Cochrane library were searched for studies published up to 15th February 2022. Studies on the association between PPI and the risk of gastric cancer, pooled the odds ratios (ORs) using a random-effects model. The subgroup analysis for study design, site of gastric cancer, and the duration of PPI use was performed. Heterogeneity was assessed using the I2 and Cochran's Q statistics. RESULTS: Sixteen cohorts and case-control studies were included. PPI use was significantly associated with gastric cancer (OR: 1.75, 95% CI: 1.28-2.40). The subgroup analysis found a significant risk increase in non-cardia gastric cancer (OR: 2.14, 95%CI: 1.50-3.07). There was no duration-dependent effect of PPI use and gastric cancer risk (< 1 year: OR: 2.56, 95% CI: 1.41-4.64, I2 = 98%; 1-3 years: OR: 1.47, 95% CI: 1.26-1.71, I2 = 41%; > 3 years: OR: 1.58, 95% CI: 1.16-2.14, I2 = 74%). CONCLUSIONS: PPIs were significantly associated with an increased risk of gastric cancer. However, this association does not confirm causation. Several well-design studies are needed to confirm the findings in the future.

Effects of various treatments for preventing oral mucositis in cancer patients: A network meta-analysis.

BACKGROUND: Oral mucositis (OM) is a common side effect of chemotherapy and radiotherapy in patients with cancers. The prevention or treatment of OM in cancer patients is crucial in the treatment of cancer. METHODS: We searched PubMed, Embase, and Cochrane Library for the randomized control trials (RCTs) of interventions for preventing and treating OM. Network meta-analysis (NMA) was performed to estimate odds ratios (ORs) and 95% confidence intervals (CI) from both direct and indirect evidence. The prespecified primary efficacy outcome was the treatment effect of moderate to severe oral mucositis with 12 interventions. The outcome was moderate to a severe grade of OM. RESULTS: This study included 55 RCTs with 3,552 participants. The results showed that honey significantly lowered the risk of chemo/radiotherapy-induced moderate to severe oral mucositis than placebo (OR: 0.01, 95%CI 0.00 to 0.45), followed by lignocaine (OR: 0.07, 95%CI 0.00 to 0.95). The surface under cumulative ranking curve (SUCRA) values for honey were 0.95, followed by lignocaine (SUCRA, 0.81) and benzydamine (SUCRA, 0.78). CONCLUSIONS: The honey is effective for patients with cancer undergoing chemotherapy or radiotherapy-induced oral mucositis.

Effectiveness of Oil Pulling for Improving Oral Health: A Meta-Analysis.

Objective: The effect of oil pulling on oral health has not yet been fully demonstrated. Therefore, we performed a meta-analysis to investigate the effect of oil pulling on oral health. Methods: We searched PubMed, the Cochrane Library, and the EMBASE database, limiting the search to human patients and articles written in English and published before 31 July 2022. We included randomized controlled trials (RCTs) comparing the effect of oil pulling on improving dental health and oral hygiene. The outcomes of this study were salivary bacteria count, plaque index, and gingival index. Results: In total, nine RCTs were included in this study. The study showed that salivary bacterial colony (BC) counts were significantly reduced in the oil pulling group compared to the control group [mean difference (MD): 17.55, 95% CI 2.56, 32.55]. There was no significant difference between the two groups (MD: -0.10, 95% CI -0.33, 0.14; -0.05, 95% CI -0.12, 0.02) in plaque index and gingival index score. Conclusions: Based on the results of this meta-analysis, the oil pulling may have a beneficial effect on reducing salivary BC count compared to the control group. There was no significant difference in the plaque index and gingival index score between the oil pulling and the control group. Therefore, future clinical trials should be more rigorous and better reported.

Therapeutic efficacy of nivolumab plus sorafenib therapy in patients with unresectable hepatocellular carcinoma.

BACKGROUND: Immune checkpoint inhibitor therapy is the backbone of numerous combination regimens for improving the therapeutic response of patients with hepatocellular carcinoma (HCC). We aimed to investigate the therapeutic efficacy of nivolumab plus sorafenib therapy in patients with unresectable HCC. METHODS: Patients with unresectable HCC who received sorafenib and followed at Taipei Tzu Chi Hospital from January 2016 to May 2022 were selected for this study, and those treated with nivolumab plus sorafenib and those with sorafenib alone were propensity score matched. The primary outcome was overall survival (OS) presented as a hazard ratio calculated using Cox proportional hazards regression models. RESULTS: In the analysis, 36 patients receiving nivolumab plus sorafenib and 36 receiving sorafenib alone were propensity score matched. The median OS for those receiving nivolumab plus sorafenib and sorafenib alone were 3.6 years and 1.2 years, respectively (p = 0.031). The hazard ratio of OS for nivolumab plus sorafenib compared to sorafenib alone was 0.36 (95 %CI, 0.19-0.70; p = 0.003). Furthermore, patients receiving nivolumab plus sorafenib with a baseline α-fetoprotein(AFP) < 10 ng/mL and early reduction in AFP had a 100 % objective response rate and disease control rate. CONCLUSION: In patients with unresectable HCC, nivolumab plus sorafenib resulted in better OS outcomes than sorafenib.

Monoclonal Antibodies for First-Line Treatment Metastatic Colorectal Cancer.

BACKGROUND: In addition to discontinuing treatment at disease progression, cumulative toxicity limitations and genetic mutations play important roles in chemotherapy choice in metastatic colorectal cancer (mCRC). However, in recent years, targeted therapies, such as immune checkpoint inhibitors or monoclonal antibodies (MoAbs), have been used with chemotherapy to improve clinical outcomes in patients with mCRC. AREAS OF UNCERTAINTY: Approximately 15% of patients with CRC would be eligible for further targeted therapy with immune checkpoint inhibitors based on genetic testing, but most patients with CRC would not qualify, especially Kirsten rat sarcoma wild-type. Therefore, adding MoAb is only an option for most patients until disease progression or unacceptable toxicity occurs. However, the results are not consistent with the combination of MoAb and different chemotherapy bases. In addition, most results from combining MoAb with different chemotherapy bases are not consistent. DATA SOURCES: This meta-analysis includes published of the PubMed and Embase databases, limited to English literature, and patients were treated with MoAb combination. Randomized control trials conducted published up to May 2021 were considered for inclusion. THERAPEUTIC ADVANCES: Fluoropyrimidine-based chemotherapy has been the backbone of palliative therapy for mCRC, with demonstrated benefits. This article will review the efficacy and safety of randomized control trials comparing different MoAb with fluoropyrimidine-based chemotherapy as first-line therapy for patients with mCRC, particularly in Kirsten rat sarcoma wild-type. CONCLUSION: This meta-analysis revealed that MoAb plus chemotherapy has better progression-free survival and objective response rate than chemotherapy alone. However, treatment-related serious adverse events (grade ≥ 3) should be considered, particularly severe rash, diarrhea, and hypertension.

Transarterial chemoembolization with or without sorafenib for hepatocellular carcinoma: A real-world propensity score-matched study.

Objectives: Transarterial chemoembolization (TACE) or sorafenib may prolong survival in patients with unresectable hepatocellular carcinoma (HCC); however, whether their combination prolongs survival than TACE alone remains controversial. We aimed to compare the overall survival (OS) of patients with unresectable HCC treated with TACE plus sorafenib (TACE-S) versus TACE alone. Materials and Methods: All patients with unresectable HCC who received TACE as the initial therapy between January 2006 and January 2017 at Taipei Tzu Chi Hospital were enrolled. We matched patients treated with TACE-S and those treated with TACE alone (TACE) by performing propensity score matching at a 1:2 ratio. Our primary outcome was OS during a 10-year follow-up period, and represented as a hazard ratio calculated using Cox proportional hazard regression models. Results: Among 515 patients with unresectable HCC were treated initially with TACE, 56 receiving TACE-S group and 112 receiving TACE alone (TACE group) were included in the primary outcome analysis. The TACE-S group had significantly longer median OS than did the TACE group (1.55 vs. 0.32, years; P < 0.001), and the 5-year OS rates was 10.7% in the TACE-S group and 0.9% in the TACE group (P < 0.001). In multivariate analyses, patients with a lower Child-Pugh score, tumor size ≤5 cm, and no extrahepatic metastasis before treatment and those receiving antiviral agents and receiving TACE-S had longer OS (all P < 0.001). Conclusion: Antiviral agents and the combination of TACE with sorafenib may improve the OS of patients with unresectable HCC.

Efficacy and safety of belimumab therapy in systemic lupus erythematosus: A systematic review and meta-analysis.

BACKGROUND: Belimumab is the first biological agent approved for the treatment of systemic lupus erythematosus (SLE). The efficacy and safety of belimumab for SLE patients are not clear. Therefore, this meta-analysis is integrating the efficacy and safety of belimumab for patients with SLE. METHODS: PubMed, EMBASE, and Cochrane Library were searched for randomized clinical trials (RCTs) that studied the efficacy and safety of belimumab plus standard therapy before November 1, 2021. Data were pooled using the random-effects model and are expressed as risk ratios (RRs) or mean difference (MD) and corresponding 95% confidence intervals (CIs). Heterogeneity was assessed and quantified using I2. RESULTS: Seven RCTs with 3,009 participants were included in this meta-analysis. Belimumab showed significantly decreased at least a 4-point improvement in Safety of Estrogen in Lupus National Assessment (SELENA)-Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score than placebo (RR, 1.32; 95% CI, 1.21-1.44; p < 0.001). However, belimumab significantly reduced the prednisone dose by 50% or more than placebo (RR, 1.59; 95% CI, 1.17-2.15; p = 0.003) and belimumab significantly increased the 36 Physical Component Summary (PCS) score (MD, 1.60; 95% CI, 0.30-2.90; p = 0.02). Regarding adverse events, there was no significant difference between the belimumab group and the control group. CONCLUSION: The results suggest that belimumab plus standard therapy is more effective than placebo plus standard therapy in SLE patients.

Efficacy and immunogenicity of insulin biosimilar compared to their reference products: a systematic review and meta-analysis.

BACKGROUND: To ascertain the efficacy, safety, and immunogenicity from existing evidence via conducting a meta-analysis of randomized controlled trials between biosimilar and originator insulins. METHODS: The PubMed, Cochrane Library, EMBASE, and ClinicalTrails.gov were searched to identify head-to-head randomized controlled trials (RCTs) that directly compare the efficacy and safety of biosimilar insulin and its originator. Efficacy was assessed by change of HbA1C, fasting plasma glucose (laboratory or self-monitoring of blood glucose (SMBG)), and change all mean of 7 points- or 8 points- SMBG. Safety was assessed by change in proportion hypoglycemia and serious hypoglycemia. The occurrence of anti-insulin antibodies (AIAs) was also evaluated. RESULTS: Fourteen RCTs with 6188 patients from different countries were included. Data were pooled using a random-effects model and were expressed as the mean difference (MD), odds ratio (OR), and 95% confidence interval (CI). In efficacy, Insulin biosimilar products showed similar in change of HbA1C at weeks 26 and 52, the MD were 0.03 (95% CI - 0.02 to 0.07, p = 0.28), and 0.05 (95% CI - 0.05 to 0.15, p = 0.36), respectively. The proportion of HbA1C less than 7% at endpoint, the OR were 1.04 (95% CI 0.89 to 1.20, p = 0.64). The change of fasting plasma glucose (laboratory or SMBG) mmol/L in 24-52 weeks and change all mean of 7 points-/8 points- SMBG mmol/L in 24-52 weeks, the MD were 0.02 (95% CI - 0.20 to 0.24, p = 0.87) and - 0.34 (95% CI - 1.35 to 0.67, p = 0.51), respectively. In occurrence of hypoglycemia (≥ 1 events) and severe hypoglycemia, the OR were 0.96 (95% CI 0.85 to 1.09, p = 0.52) and 1.06 (95% CI 0.85 to 1.31, p = 0.62). The AIA was 1.02 (95% CI 0.90 to 1.16, p = 0.76). Analysis stratified by type of diabetes and duration of insulin. There was no significant difference between the biosimilar and their reference group in a different type of diabetes and different duration of insulin. CONCLUSIONS: Insulin biosimilar showed comparable characteristics with the reference drug in terms of efficacy, safety, immunogenicity, through comprehensive and specific conventional meta-analysis.

Immune checkpoint inhibitors for first-line treatment of advanced non-small-cell lung cancer: A systematic review and network meta-analysis.

OBJECTIVE: Currently, several immune checkpoint inhibitors (ICIs) treatment for advanced non-small-cell lung cancer (NSCLC) have been investigated; their overall efficacy and safety remain unclear. METHODS: We searched electronic databases such as PubMed, EMBASE, and the Cochrane library. The randomized controlled trials (RCTs) that compared ICIs with or without chemotherapy to chemotherapy in advanced NSCLC. We collected and compaired thier parameters, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs) of grade ≥3. RESULTS: A total of 15 RCTs involving 8869 patients with NSCLC were included. Pembrolizumab plus platinum-based chemotherapy had higher OS and PFS than platinum-based chemotherapy (hazard ratio [HR] 0.55, 95% CI 0.46-0.67; HR 0.54, 95% CI 0.41-0.70, respectively). Pembrolizumab plus platinum-based chemotherapy had higher ranked ORR than platinum-based chemotherapy (odds ratio [OR] 2.92, 95% CI 1.99-4.22). In terms of OS, atezolizumab, pembrolizumab plus platinum-based chemotherapy, and nivolumab plus ipilimumab ranked as the best treatments for patients with programmed death-ligand 1 (PD-L1) expression levels of ≥50%, 1-49%, and <1%, respectively. In terms of PFS, pembrolizumab plus platinum-based chemotherapy ranked as the best treatment for patients with any PD-L1 expression levels. However, ipilimumab plus platinum-based chemotherapy, nivolumab plus platinum-based chemotherapy, and atezolizumab plus platinum-based chemotherapy have higher TRAEs of grade ≥3 than platinum-based chemotherapy. CONCLUSIONS: Pembrolizumab plus platinum-based chemotherapy prevailed in rank in OS, PFS, and ORR benefit. The TRAEs of pembrolizumab plus platinum-based chemotherapy were more than ICI monotherapy and chemotherapy.

Effectiveness of glutamine in the management of oral mucositis in cancer patients: a meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this meta-analysis was to evaluate the effectiveness of glutamine for preventing or treating moderate-to-severe oral mucositis induced by chemotherapy or radiation therapy in patients with cancer. METHODS: PubMed, Cochrane Library, and Embase were searched for eligible randomized controlled trials (RCTs) up to June 2020. The outcomes analyzed were oral mucositis (at all levels of severity). Data were pooled using the random-effects model and are expressed as risk ratios (RRs) and corresponding 95% confidence intervals (CIs). Heterogeneity was assessed and quantified using I2. RESULTS: Sixteen RCTs were included in this review. In this meta-analysis, compared with placebo, glutamine significantly reduced the incidence of grade 3 and 4 oral mucositis induced by chemotherapy or radiation therapy (RR, 0.53; 95% CI, 0.32-0.88). In subgroup analysis, oral glutamine administration (RR, 0.56; 95% CI, 0.34-0.92) and a medium or low daily dose of glutamine (RR, 0.58; 95% CI, 0.44-0.77; RR, 0.53; 95% CI, 0.28-0.94; respectively) decreased risk. Glutamine caused a borderline significant reduction in the risk of grade 3 and 4 oral mucositis induced by radiotherapy (RR, 0.75; 95% CI, 0.58-0.99) and especially in its prevention (RR, 0.51; 95% CI, 0.28-0.94). CONCLUSIONS: Glutamine significantly reduces the risk of oral mucositis during chemotherapy or radiation therapy. Furthermore, large prospective trials are required to support these findings.

Radiofrequency ablation versus surgical resection for the treatment of solitary hepatocellular carcinoma 2 cm or smaller: A cohort study in Taiwan.

BACKGROUND/PURPOSE: Radiofrequency ablation (RFA) is increasingly being used instead of surgical resection for the treatment of hepatocellular carcinoma (HCC) tumor measuring ≦2 cm. However, the long-term outcomes of RFA, especially in comparison to surgical resection, are still debated. We compared the outcomes of surgical resection and RFA in patients with a solitary HCC tumor measuring ≦2 cm from a 10-year cohort study. METHODS: From Jan 2006 to Dec 2016, 156 patients with a resectable HCC measuring ≦2 cm who underwent surgical resection (n = 83) or RFA (n = 73) at the Buddhist Tzu Chi Medical Foundation were enrolled. Patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were retrospectively examined, and comparisons were made between the two groups and through subgroup analyses. RESULTS: The 1-year, 3-year, 5-year, and 7-year OS outcomes were comparable between the surgical resection group and the RFA group (P = 0.193), but the surgical resection group had significantly higher 1-year, 3-year, 5-year, 7-year, and 10-year RFS than the RFA group (P = 0.018). Multivariate analysis revealed that patients with lower age, Child-Turcotte-Pugh score, or albumin-bilirubin score before treatment had better OS, and patients with an HCV infection or receiving RFA treatment had higher HCC recurrence rates. CONCLUSION: The liver reserve determined the long-term OS of patients with an HCC tumor ≦ 2 cm, and surgical resection offered better RFS than RFA (ClinicalTrials.gov number, NCT04525833.).

Hypnotics and Risk of Cancer: A Meta-Analysis of Observational Studies.

Background and objectives: The association between hypnotic drugs and risk of cancer remains controversial. Therefore, we performed a meta-analysis to investigate this association. Materials and Methods: Pubmed and Embase were searched systematically to identify publications up to April 2020. The Newcastle-Ottawa scale for observational studies was used to assess the quality of studies. All included studies were evaluated by two reviewers independently; any discrepancies were resolved through discussion. Results: Twenty-eight studies including 22 case-control studies and 6 cohort studies with 340,614 hypnotics users and 1,828,057 non-users were included in the final analyses. Hypnotics (benzodiazepines and Z-drugs) use was significantly associated with an increased risk of cancer (odds ratio [OR] or relative risk [RR] 1.17; 95% confidence interval 1.09-1.26) in a random-effects meta-analysis of all studies. Subgroup meta-analysis by anxiolytics/sedatives effect (anxiolytics benzodiazepines vs. sedatives group (include sedatives benzodiazepines and Z-drugs)) revealed that a significant association in sedatives group (pooled OR/RR 1.26, 95% CI, 1.10-1.45), whereas no significant relationship was observed in anxiolytics benzodiazepines (pooled OR/RR 1.09, 95% CI, 0.95-1.26). Moreover, a significant dose-response relationship was observed between the use of hypnotics and the risk of cancer. Conclusions: This meta-analysis revealed association between use of hypnotics drugs and risk of cancer. However, the use of lower dose hypnotics and shorter duration exposed to hypnotics seemed to be not associated with an increased risk of cancer. Moreover, the use of anxiolytics effect benzodiazepines seemed to be lower risk than sedatives benzodiazepines. A high heterogeneity was observed among identified studies, and results were inconsistent in some subgroups. Randomized control trials are needed to confirm the findings in the future.