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Cancer Medicine Jan 2023This meta-analysis was conducted to evaluate the efficacy and safety of the addition of Traditional Chinese Medicine (TCMs) to capecitabine-based regimens for colorectal... (Meta-Analysis)
Meta-Analysis
This meta-analysis was conducted to evaluate the efficacy and safety of the addition of Traditional Chinese Medicine (TCMs) to capecitabine-based regimens for colorectal cancer (CRC) in term of tumor. The eight electronic databases including Cochrane Library, PubMed, Web of Science (WOS), Excerpt Medica Database (Embase), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journals (CQVIP), and Wanfang Database were systematically searched for eligible studies from their inception to March 2021. Thirty-nine randomized controlled trials were involved in this study, and all the data were analyzed by Review Manager 5.3 (Nordic Cochran Centre, Copenhagen, Denmark) and R 4.0.5 software. The meta-analyses suggested that TCMs in combination with capecitabine-based regimens increased objective response rate (ORR) in the palliative treatment of CRC (risk ratio [RR], 1.35 [1.17, 1.55], I = 0%), disease control rate (DCR) (RR, 1.22 [1.12, 1.32], I = 3%), and quality of life (QOL) (RR, 1.71 [1.44, 2.03], I = 0%), with decreased risks of myelosuppression, anemia, thrombocytopenia, liver/renal dysfunction, neurotoxicity, nausea/vomiting, neutropenia, diarrhea, leukopenia, improved the peripheral lymphocyte, reduced the expression of tumor markers, and related factors. Further sensitivity analysis of specific plant-based TCMs found that dangshen, fuling, and gancao had significantly higher contributions to the results of the RR. The results show that capecitabine-based chemotherapy combined with TCM in the treatment of CRC increases the efficiency of ORR and DCR, reduces chemotherapeutic agents-associated adverse reactions, and improves their life quality as compared with chemotherapy alone, but further randomized and large sample of studies are needed.
Topics: Humans; Medicine, Chinese Traditional; Capecitabine; Quality of Life; Drugs, Chinese Herbal; Neutropenia; Colorectal Neoplasms; Randomized Controlled Trials as Topic
PubMed: 35650714
DOI: 10.1002/cam4.4896 -
Frontiers in Neurology 2024The efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with whole-brain radiotherapy (WBRT) for treating brain...
BACKGROUND
The efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with whole-brain radiotherapy (WBRT) for treating brain metastases in non-small cell lung cancer patients remains to be determined.
METHODS
A systematic search was conducted using databases including PubMed, Embase, Web of Science, Cochrane, Wanfang, and China National Knowledge Infrastructure (CNKI), aiming to identify relevant clinical studies on the treatment of brain metastases originating from non-small cell lung cancer through the combination of EGFR-TKI and WBRT. Statistical analysis was performed utilizing Stata 17.0 software, covering clinical studies published until March 1, 2023.
RESULTS
This analysis incorporated 23 randomized controlled trials (RCTs), involving a total of 2,025 patients. Of these, 1,011 were allocated to the group receiving both EGFR-TKI and WBRT, while 1,014 were assigned to the WBRT alone group. The findings reveal that the combination of EGFR-TKI and WBRT significantly improves the intracranial objective remission rate (RR = 1.57, 95% CI: 1.42-1.74, < 0.001), increases the intracranial disease control rate (RR = 1.30, 95% CI: 1.23-1.37, < 0.001), and enhances the 1-year survival rate (RR = 1.48, 95% CI: 1.26-1.73, < 0.001). Additionally, this combined treatment was associated with a significant survival advantage (RR = 1.48, 95% CI: 1.26-1.73, < 0.001) and a reduced incidence of adverse effects (RR = 0.65, 95% CI: 0.51-0.83, < 0.001), particularly with respect to nausea and vomiting (RR = 0.54, 95% CI: 0.37-0.81, = 0.002) and myelosuppression (RR = 0.59, 95% CI: 0.40-0.87, = 0.008). However, no statistically significant differences were observed for diarrhea (RR = 1.15, 95% CI: 0.82-1.62, = 0.418), and skin rash (RR = 1.35, 95% CI: 0.88-2.07, = 0.164).
CONCLUSION
In contrast to WBRT alone, the combination of EGFR-TKI and WBRT significantly improves intracranial response, enhancing the objective response rate, disease control rate, and 1-year survival rate in NSCLC patients with brain metastases. Moreover, aside from mild cases of rash and diarrhea, there is no statistically significant increase in the incidence of additional adverse effects. Based on the comprehensive evidence collected, the use of third-generation EGFR-TKI combined with WBRT is recommended as the preferred treatment for NSCLC patients with brain metastases, offering superior management of metastatic brain lesions.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/#, CRD42023415566.
PubMed: 38737351
DOI: 10.3389/fneur.2024.1362061 -
Frontiers in Medicine 2021Immune checkpoint inhibitors (ICIs) have previously been reported to have a promising potential in terms of the improvement of outcomes in non-small cell lung cancer...
Immune checkpoint inhibitors (ICIs) have previously been reported to have a promising potential in terms of the improvement of outcomes in non-small cell lung cancer (NSCLC). Fatal adverse events (FAEs) of ICIs are relatively uncommon, and the incidence and risk in NSCLC remain unclear. In the present study, we conducted a systematic review and meta-analysis to evaluate the risk of FAEs in NSCLC patients administered with ICIs. Potentially relevant studies were identified in PubMed, EMBASE, and Cochrane library database from inception to September 16, 2020. The systematic review and meta-analysis included randomized controlled trials that reported treatment-related FAEs in NSCLC. The pooled incidence and risk ratios (RRs) were calculated to evaluate prospective risk. Twenty clinical trials that included a total of 13,483 patients were selected for the meta-analysis. The overall incidence of FAEs was 0.65% [95% confidence interval (CI) = 0.31-1.07, = 50.2%] in ICI monotherapy, 1.17% (95% CI = 0.74-1.69, = 56.3%) in chemotherapy, and 2.01% (95% CI = 1.42-2.69, = 5.9%) in the combination therapy (ICI and chemotherapy). ICI monotherapy was associated with lower incidence of FAEs caused by blood system disorders (RR = 0.23, 95% CI = 0.07-0.73, = 0.013, = 0%) and infectious diseases (RR = 0.29, 95% CI = 0.13-0.63, = 0.002, = 0%). The incidence of pneumonitis significantly increased in immunotherapy (RR = 5.72, 95% CI = 1.14-28.80, = 0.03, = 0%). The results of the present study demonstrate that ICI monotherapy decreases the risk of FAEs, whereas the combined regimens with chemotherapy have the opposite tendency as compared to conventional chemotherapy. While the patients who received chemotherapy suffered the risks of death mainly from myelosuppression and infection, those who received immunotherapy were mainly threatened by immune-related pneumonitis.
PubMed: 33659263
DOI: 10.3389/fmed.2021.627089 -
Current Problems in Cancer Dec 2020CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors are both emerging agents for hormonal receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative... (Comparative Study)
Comparative Study Meta-Analysis
Comparative efficacy and safety of CDK4/6 and PI3K/AKT/mTOR inhibitors in women with hormone receptor-positive, HER2-negative metastatic breast cancer: a systematic review and network meta-analysis.
BACKGROUND
CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors are both emerging agents for hormonal receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer. Evidence for the comparisons from head-to-head comparative trials is currently insufficient. This meta-analysis assessed the comparative efficacy and safety of these two groups of agents for HR+/HER2- metastatic breast cancer.
METHODS
Systematic searches of PubMed, Embase, CENTRAL, SciSearch between January 2010 to December 2019 were conducted. Randomized controlled trials (RCTs) which evaluated clinical benefits and toxicities of CDK4/6 inhibitors or PI3K/AKT/mTOR inhibitors plus endocrine therapy were adopted. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoint was treatment-related adverse event (TRAE). Pooled hazard ratio (HR) and risk rate (RR) were used to assess the differences between CDK4/6 and PI3K/AKT/mTOR inhibitors.
RESULTS
A total of twenty RCTs including 9771 participants were identified in this study. Pooled results showed that PFS was considerably prolonged by targeted therapy plus endocrine therapy. PFS was relatively better in CDK4/6 inhibitors than that of PI3K inhibitor group (HR, 1.43; 95%CrI, 1.12-1.61). Similar results were demonstrated in results after balancing lines of therapy or metastatic sites, both in viscera and bone-only. Coalesced outcomes revealed that CDK4/6 inhibitors plus endocrine therapy could significantly improve OS (HR, 0.78; 95%CrI, 0.65-0.94) than PI3K/mTOR inhibitors. Safety profiles of diarrhea and rash were consistent between CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors with no difference of estimated RR. Several TRAEs signified specificity, for instance, myelosuppression in CDK4/6 inhibitors or hyperglycemia in PI3K/mTOR inhibitors.
CONCLUSIONS
Clinical efficacy is in favor of CDK4/6 inhibitors, and safety profiles are comparable between CDK4/6 inhibitors or PI3K/AKT/mTOR inhibitors plus endocrine therapy.
Topics: Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Female; Humans; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; TOR Serine-Threonine Kinases
PubMed: 32446638
DOI: 10.1016/j.currproblcancer.2020.100606 -
The International Journal of... Dec 2019Studies have shown that linezolid (LZD) can be used to treat extensively drug-resistant tuberculosis (XDR-TB). To conduct a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
Studies have shown that linezolid (LZD) can be used to treat extensively drug-resistant tuberculosis (XDR-TB). To conduct a systematic review and meta-analysis to assess existing evidence concerning efficacy and safety of LZD for XDR-TB treatment. The MEDLINE@OVID, PubMed, EMBASE, the Cochrane Library, Clinical Trials, Sinomed, CMCI, CNKI, VIP and Wanfang databases were systematically searched for randomised controlled trials, cohort studies, case series or case reports on XDR-TB patients treated with LZD from January 2000 to December 2016. Summary estimates of the rate of sputum culture conversion, treatment success and adverse effects were calculated; data that could not be combined were summarised and described qualitatively. The combined results were examined for heterogeneity, sensitivity and publishing bias. Twenty-two original studies covering a total of 302 patients with XDR-TB fulfilled the inclusion criteria. Pooled estimates for sputum culture conversion and treatment success rates were respectively 93.2% and 67.4% in XDR-TB patients on LZD treatment. The pooled estimates for the rate of myelosuppression, peripheral neuropathy, optic neuritis and adverse reactions of the gastrointestinal tract were respectively 42.5%, 26.0%, 19.0% and 35.0%. Heterogeneity was mostly due to the initial dose of LZD (≤600 mg/d or >600 mg/d), as patients with a high initial dose of LZD were more likely to have myelosuppression (48.4% vs. 24.8%, = 0.010) and adverse events of the gastrointestinal tract (41.3% vs.15.4%, = 0.100). LZD appears to be effective for XDR-TB, but adverse events are common. An LZD dose of ≤600 mg/d as the initial dose for treating XDR-TB patients is recommended.
Topics: Antitubercular Agents; Extensively Drug-Resistant Tuberculosis; Humans; Linezolid; Tuberculosis, Pulmonary
PubMed: 31931914
DOI: 10.5588/ijtld.18.0822 -
Haematologica Apr 20246-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene... (Meta-Analysis)
Meta-Analysis
Association of gene polymorphism with adverse reaction, treatment efficacy, and dose of 6-mercaptopurine in patients with acute lymphoblastic leukemia: a systematic review and meta-analysis.
6-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene polymorphism on the risk of myelosupression, hepatotoxicity and interruption of 6-MP, as well as treatment efficacy and dose of 6-MP in ALL patients. A total of 24 studies with 3,374 patients were included in this meta-analysis. We found 9-fold higher risk of 6-MP induced leukopenia (odds ratio [OR] =9.00, 95% confidence interval [CI]: 3.73-21.74) and 2.5-fold higher risk of 6-MP-induced neutropenia (OR=2.52, 95% CI: 1.72-3.69) for NUDT15 c.415C>T variant carriers in the dominant model. Moreover, we found that the dose intensity of 6-MP in ALL patients with one NUDT15 c.415C>T variant alleles (CT) was 19% less than that in wild-type patients (CC) (mean differences: 19.43%, 95% CI: -25.36 to -13.51). The tolerable dose intensity of 6-MP in NUDT15 c.415C>T homozygote variant (TT) and heterozygote variant (CT) carriers was 49% and 15% less than that in wild-type patients, respectively. The NUDT15 c.415C>T variant group (CT+TT) had seven times (OR=6.98, 95% CI: 2.83-17.22) higher risk of developing 6-MP intolerance than the CC group. However, NUDT15 c.415C>T polymorphism did not appear significantly associated with hepatotoxicity, treatment interruption or relapse incidence. We concluded that NUDT15 c.415C>T was a good predictor for 6-MP-induced myelosuppression in ALL patients. The dose intensity of 6-MP in ALL patients with NUDT15 c.415C>T variants was significantly lower than that in wild-type patients. This research provided a basis for further investigation into relations between NUDT15 gene and adverse reaction, treatment efficacy and dose intensity of 6-MP.
Topics: Humans; Mercaptopurine; Pyrophosphatases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Polymorphism, Genetic; Neutropenia; Treatment Outcome; Chemical and Drug Induced Liver Injury
PubMed: 37794799
DOI: 10.3324/haematol.2023.282761 -
Frontiers in Pharmacology 2022Immunosuppressants have been applied in the remedy of idiopathic membranous nephropathy (IMN) extensively. Nevertheless, the efficacy and safety of immunosuppressants...
Immunosuppressants have been applied in the remedy of idiopathic membranous nephropathy (IMN) extensively. Nevertheless, the efficacy and safety of immunosuppressants do not have final conclusion. Thus, a pairwise and network meta-analysis (NMA) was carried out to seek the most recommended therapeutic schedule for patients with IMN. Randomized controlled trials (RCTs) including cyclophosphamide (CTX), mycophenolate mofetil (MMF), tacrolimus-combined mycophenolate mofetil (TAC + MMF), cyclosporine (CsA), tacrolimus (TAC), leflunomide (LEF), chlorambucil (CH), azathioprine (AZA), adrenocorticotropic hormone (ACTH), non-immunosuppressive therapies (CON), steroids (STE), mizoribine (MZB), and rituximab (RIT) for patients with IMN were checked. Risk ratios (RRs) and standard mean difference (SMD) were reckoned to assess dichotomous variable quantities and continuous variable quantities, respectively. Total remission (TR) and 24-h urine total protein (24-h UTP) were compared using pairwise and NMA. Then interventions were ranked on the basis of the surface under the cumulative ranking curve (SUCRA). Our study finally included 51 RCTs and 12 different immunosuppressants. Compared with the CON group, most regimens demonstrated better therapeutic effect in TR, with RR of 2.1 (95% CI) (1.5-2.9) for TAC, 1.9 (1.3-2.8) for RIT, 2.5 (1.2-5.2) for TAC + MMF, 1.9 (1.4-2.7) for CH, 1.8 (1.4-2.4) for CTX, 2.2 (1.0-4.7) for ACTH, 1.6 (1.2-2.1) for CsA, 1.6 (1.0-2.5) for LEF, and 1.6 (1.1-2.2) for MMF. In terms of 24-h UTP, TAC (SMD, -2.3 (95% CI -3.5 to -1.1)), CTX (SMD, -1.7 (95% CI -2.8 to -0.59)), RIT (SMD, -1.8 (95% CI -3.5 to -0.11)), CH (SMD, -2.4 (95% CI -4.3 to -0.49)), AZA (SMD, --4.2 (95% CI -7.7 to -0.68)), and CsA (SMD, -1.7 (95% CI -3 to -0.49)) were significantly superior than the CON group. As for adverse effects (AEs), infections, nausea, emesia, myelosuppression, and glucose intolerance were the collective adverse events for most immunosuppressants. This study indicates that TAC + MMF performed the best in terms of TR, and TAC shows the best effectiveness on 24-h UTP compared with other regimens. On the contrary, there seems to be little advantage on STE alone, LEF, AZA, and MZB in treating patients with IMN compared with CON. [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021287013].
PubMed: 35959430
DOI: 10.3389/fphar.2022.917532 -
Bioscience Reports Aug 2020Huaier Granule, a type of traditional Chinese biomedical preparation (TCBP), is considered to be a promising adjuvant therapy for breast cancer. Although an analysis of... (Meta-Analysis)
Meta-Analysis
Huaier Granule, a type of traditional Chinese biomedical preparation (TCBP), is considered to be a promising adjuvant therapy for breast cancer. Although an analysis of the published literature has been performed, the exact effects and safety of Huaier Granule remains controversial. Therefore, a wide-ranging systematic search of electronic databases from which to draw conclusions was performed. Data from 27 trials, including 2562 patients with breast cancer were analyzed. The results indicated that, compared with conventional treatment alone, the combination of conventional treatment and Huaier Granule markedly improved patients' overall response (P=0.02) and quality of life (P<0.00001), and significantly prolonged 2-year (P=0.02), 3-year (P<0.0001) and 5-year (P=0.004) overall survival rates, and 1-year (P=0.003), 2-year (P<0.00001), 3-year (P<0.00001) and 5-year (P=0.03) disease-free survival. The immune function of patients was also significantly enhanced after combined intervention treatment, indicated by clearly increased percentages of CD3+ (P=0.05), CD4+ (P<0.00001) and natural killer cells (P<0.0001), and CD4+/CD8+ ratio (P<0.00001). The incidence of myelosuppression (P=0.001) and hepatotoxicity (P=0.05) was lower in breast cancer patients treated with Huaier Granule, whereas other adverse events did not differ significantly between the two groups (P>0.05). In summary, results of this meta-analysis suggest that the combination of conventional treatment and Huaier Granule is more effective for the treatment of breast cancer than conventional treatment alone.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Complex Mixtures; Controlled Clinical Trials as Topic; Female; Humans; Middle Aged; Time Factors; Trametes; Treatment Outcome
PubMed: 32789470
DOI: 10.1042/BSR20202509 -
BMC Cancer Oct 2020Both intermittent intravenous (IIV) infusion and continuous intravenous (CIV) infusion of Endostar are widely used for NSCLC in China. We aimed to compare the efficacy... (Comparative Study)
Comparative Study Meta-Analysis
Endostar continuous versus intermittent intravenous infusion combined with chemotherapy for advanced NSCLC: a systematic review and meta-analysis including non-randomized studies.
BACKGROUND
Both intermittent intravenous (IIV) infusion and continuous intravenous (CIV) infusion of Endostar are widely used for NSCLC in China. We aimed to compare the efficacy and safety of CIV of Endostar versus IIV in combination with first-line chemotherapy for patients with advanced NSCLC.
METHODS
RCTs, NRCTs and cohort studies which compared CIV of Endostar with IIV in advanced NSCLC patients and reported efficacy or safety outcomes were eligible. Two reviewers independently screened records, extracted data and assessed risk of bias. Pooled risk ratios (RRs) with 95% confidence intervals were calculated using random effects meta-analysis for short-term efficacy and safety outcomes, and hazard ratios (HRs) for survival outcomes.
RESULTS
Finally nine studies involving 597 patients were included, containing two RCTs, three NRCTs and four cohort studies. For short-term efficacy, moderate quality of evidence showed that there were no significant differences between CIV of Endostar and IIV in objective response rate (ORR; RR 1.34, 95% CI 0.91-1.98, P = 0.14) and disease control rate (DCR; RR 1.11, 95% CI 0.94-1.30, P = 0.21). Very low quality of evidence indicated that CIV of Endostar significantly improved both overall survival (OS; HR 0.69, 95% CI 0.48-0.99, P = 0.046) and progression-free survival (PFS; HR 0.71, 95% CI 0.55-0.93, P = 0.01) compared with IIV. As for safety outcomes, moderate quality of evidence found that CIV of Endostar significantly reduced the risk of myelosuppression (RR 0.55, 95% CI 0.32-0.96, P = 0.03) and cardiovascular toxicity (RR 0.21, 95% CI 0.06-0.78, P = 0.02) compared with IIV.
CONCLUSIONS
In advanced NSCLC, compared with IIV, CIV of Endostar had similar short-term efficacy, and substantially lower risk of myelosuppression and cardiovascular toxicity. Although very low quality of evidence supported the survival benefit of CIV compared with IIV, large RCTs with long-term follow-up are needed to demonstrate survival benefits. Caution should be given for off-label use of CIV of Endostar.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; China; Drug Therapy; Endostatins; Humans; Infusions, Intravenous; Lung Neoplasms; Non-Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Analysis; Treatment Outcome
PubMed: 33087103
DOI: 10.1186/s12885-020-07527-4 -
Clinical Lymphoma, Myeloma & Leukemia Feb 2023The global incidence of myelodysplastic syndromes (MDS) has been estimated as 0.06 to 0.26/100,000. Since their introduction, hypomethylating agents have played a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The global incidence of myelodysplastic syndromes (MDS) has been estimated as 0.06 to 0.26/100,000. Since their introduction, hypomethylating agents have played a central role in the treatment of MDS, with heterogeneous real-world outcomes.
MATERIALS AND METHODS
We assessed and synthesized clinical outcomes of azacitidine (AZA) monotherapy in treatment-naïve patients with higher-risk MDS. A systematic literature review was conducted by searching MEDLINE, Embase, and CENTRAL to identify randomized clinical trials (RCTs) and observational studies, both prospective and retrospective, reporting complete remission (CR), partial remission (PR), overall survival (OS), duration of response (DOR), time-to-response (TTR), and myelosuppressive adverse events (AEs) for patients treated with AZA monotherapy. Noncomparative meta-analyses were used to summarize effects.
RESULTS
The search identified 3250 abstracts, of which 34 publications describing 16 studies (5 RCTs, 3 prospective, and 8 retrospective observational) were included. Across all studies, pooled CR was 16%; PR was 6%; Median OS was 16.4 months; median DOR was 10.1 months; median TTR was 4.6 months. Proportions of grade 3/4 anemia and thrombocytopenia AEs were 10% and 30%.
CONCLUSIONS
The effectiveness and efficacy of AZA monotherapy-as measured by CR and median OS-was limited. These findings highlight a significant unmet medical need for effective treatments for patients with higher-risk MDS.
Topics: Humans; Azacitidine; Antimetabolites, Antineoplastic; Myelodysplastic Syndromes; Treatment Outcome; Remission Induction
PubMed: 36428152
DOI: 10.1016/j.clml.2022.11.002