Effectiveness and Safety of Chinese Herbal Injections Combined with Fluoropyrimidine and Oxaliplatin-based Chemotherapy for Advanced Colorectal Cancer: A Systematic Review and Meta-analysis of 63 Randomized Controlled Trials
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SUBMITTER: Wang S
PROVIDER: S-EPMC8558662 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Numerous studies have indicated that some Chinese herbal injections (CHIs) might have a beneficial treatment effect when used in combination with chemotherapy. However, the results of these studies have been inconsistent. The aim of this network meta-analysis (NMA) was to evaluate and compare the clinical efficacy and safety of different CHIs combined with gemcitabine plus cisplatin (GP) regimen chemotherapy with that of GP regimen chemotherapy alone in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: Eight databases were systematically searched to identify randomized clinical trials (RCTs) from the date of inception of the database to August 11, 2021. The primary outcome measures were the objective response rate (ORR) and adverse reactions (including nausea and vomiting, and leukopenia). The secondary outcome measures were median survival time (MST) and quality of life (QOL). The quality of the included studies was assessed using the Cochrane risk of bias tool. Standard pair-wise and Bayesian NMAs were carried out to compare the effectiveness and safety of different CHIs combined with GP regimen chemotherapy using WinBUGS 14 and Stata 15.1 software. Sensitivity analysis and Egger's test were also performed to check robust. Results: A total of 92 eligible RCTs involving 7,728 patients and 10 CHIs were included. The results showed that Kangai injection (KAI), Kanglaite injection (KLT), Aidi injection and Compound Kushen (CKSI) injection displayed obvious advantages in both efficacy and safety. Aidi+GP (79.0%) showed great advantages of ORR, and KAI+GP and KLT+GP had the lowest probability in terms of leukopenia (4.4%) and nausea and vomiting (24.2%). Besides, KLT+GP was shown to positively affect MST. According to the subgroup analyses, CHIs might have a limited effect in reducing adverse reactions, and have a similar effect in squamous cell carcinoma and adenocarcinoma. Conclusions: KAI+GP of adjuvant drugs, Aidi+GP and CKSI+GP of anticancer drugs appeared to be the advantageous treatment options for patients with advanced NSCLC, owing to its superior therapeutic performance and reduced adverse reactions. KLT+GP might prolong survival. Nevertheless, additional results from multicenter trials and high-quality studies will be pivotal in supporting our findings.
| S-EPMC8771519 | biostudies-literature
Project description:BackgroundThis study sought to use a network meta-analysis to assess the effectiveness and safety of Chinese herbal injections (CHIs) combined with the chemotherapy for the treatment of pancreatic cancer.MethodsRandomized controlled trials (RCTs) regarding CHIs to treat pancreatic cancer were searched in PubMed, the Cochrane library, Embase, the China National Knowledge Infrastructure Database (CNKI), the Wan-Fang Database, the Chinese Scientific Journals Full-text Database (VIP), and the Chinese Biomedical Literature Database (SinoMed) up to November 2016. The quality assessment was conducted by the Cochrane risk of bias tool and network meta-analysis was performed to compare the effectiveness and safety of different CHIs combined with the chemotherapy. Data were analyzed using STATA 12.0 and Win-BUGS 1.4 software.ResultsA total of 278 records were searched, and 22 eligible RCTs involving 1329 patients and 9 CHIs were included. The results of the network meta-analysis demonstrated that compared with the chemotherapy alone, Compound Kushen, Kangai or Kanglaite injection combined with chemotherapy yielded significantly higher probability of improving performance status. Aidi injection combined with chemotherapy was more effective in relieving leucopenia than using chemotherapy single. And these between-group differences were statistically significant. However, CHIs combined with chemotherapy could not achieve a better effect in the total clinical effect, nausea and vomiting. As for the cluster analysis for the adverse reactions (ADRs), the chemotherapy alone and Huachansu injection combined with the chemotherapy were inferior to relieve ADRs than the other CHIs plus chemotherapy for patients with pancreatic cancer.ConclusionsThe current evidence showed that using CHIs on the basis of the chemotherapy could be beneficial for patients with pancreatic cancer in improving performance status and reducing the ADRs.
| S-EPMC5457895 | biostudies-literature
Project description:Introduction: The incidence and mortality of gastric cancer ranks among the highest, and the 5-year survival rate of advanced gastric cancer (AGC) is less than 10%. Currently, chemotherapy is the main treatment for AGC, and oxaliplatin is an important part of the commonly used chemotherapy regimen for AGC. A large number of RCTs have shown that Chinese herbal medicine (CHM) combined with oxaliplatin-based chemotherapy can improve objective response rate (ORR) and disease control rate (DCR), reduce the toxic and side effects of chemotherapy. There is currently a lack of systematic evaluation of the evidence to account for the efficacy and safety of CHM combined with oxaliplatin-based chemotherapy in AGC. Therefore, we carried out this study and conducted the sensitivity analysis on the herbal composition to explore the potential anti-tumor efficacy. Methods: Databases of PubMed, EMBASE, CENTRAL, Web of Science, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, the Wanfang database, and the Chinese Scientific Journals Database were searched from their inception to April 2022. RCTs evaluating the efficacy of CHM combined with oxaliplatin-based chemotherapy on AGC were included. Stata 16 was used for data synthesis, RoB 2 for quality evaluation of included RCTs, and GRADE for quality of synthesized evidence. Additional sensitivity analysis was performed to explore the potential anti-tumor effects of single herbs and combination of herbs. Results: Forty trials involving 3,029 participants were included. Most included RCTs were assessed as "Some concerns" of risk of bias. Meta-analyses showed that compare to oxaliplatin-based chemotherapy alone, that CHM combined with oxaliplatin-based chemotherapy could increase the objective response rate (ORR) by 35% [risk ratio (RR) = 1.35, 95% confidence intervals (CI) (1.25, 1.45)], and disease control rate (DCR) by 12% [RR = 1.12, 95% CI (1.08, 1.16)]. Subgroup analysis showed that compare to SOX, FOLFOX, and XELOX regimens alone, CHM plus SOX, CHM plus FOLFOX, and CHM plus XELOX could significantly increase the ORR and DCR. Sensitivity analysis identified seven herbs of Astragalus, Liquorice, Poria, Largehead Atractylodes, Chinese Angelica, Codonopsis, and Tangerine Peel with potentials to improve tumor response of oxaliplatin-based chemotherapy in AGC. Conclusion: Synthesized evidence showed moderate certainty that CHM plus oxaliplatin-based chemotherapy may promote improvement in tumor response in AGC. CHM treatment is safe for AGC. Due to the poor quality of included RCTs and small samplesizes, the quality of synthesized evidence was not high. Specific combinations of herbs appeared to produce higher contributions to ORR than the herb individually. Each of this seven above mentioned herbs has been shown in experimental studies to potentially contribute to the improvement of tumor response. To support this conclusion, these seven herbs are worthy of further clinical research. Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=262595], identifier [CRD42022262595].
| S-EPMC9453215 | biostudies-literature
Project description:BackgroundWhen cure is impossible, cancer treatment should focus on both length and quality of life. Maximisation of time without toxic effects could be one effective strategy to achieve both of these goals. The COIN trial assessed preplanned treatment holidays in advanced colorectal cancer to achieve this aim.MethodsCOIN was a randomised controlled trial in patients with previously untreated advanced colorectal cancer. Patients received either continuous oxaliplatin and fluoropyrimidine combination (arm A), continuous chemotherapy plus cetuximab (arm B), or intermittent (arm C) chemotherapy. In arms A and B, treatment continued until development of progressive disease, cumulative toxic effects, or the patient chose to stop. In arm C, patients who had not progressed at their 12-week scan started a chemotherapy-free interval until evidence of disease progression, when the same treatment was restarted. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and B is described in a companion paper. Here, we compare arms A and C, with the primary objective of establishing whether overall survival on intermittent therapy was non-inferior to that on continuous therapy, with a predefined non-inferiority boundary of 1.162. Intention-to-treat (ITT) and per-protocol analyses were done. This trial is registered, ISRCTN27286448.Findings1630 patients were randomly assigned to treatment groups (815 to continuous and 815 to intermittent therapy). Median survival in the ITT population (n=815 in both groups) was 15.8 months (IQR 9.4-26.1) in arm A and 14.4 months (8.0-24.7) in arm C (hazard ratio [HR] 1.084, 80% CI 1.008-1.165). In the per-protocol population (arm A, n=467; arm C, n=511), median survival was 19.6 months (13.0-28.1) in arm A and 18.0 months (12.1-29.3) in arm C (HR 1.087, 0.986-1.198). The upper limits of CIs for HRs in both analyses were greater than the predefined non-inferiority boundary. Preplanned subgroup analyses in the per-protocol population showed that a raised baseline platelet count, defined as 400,000 per μL or higher (271 [28%] of 978 patients), was associated with poor survival with intermittent chemotherapy: the HR for comparison of arm C and arm A in patients with a normal platelet count was 0.96 (95% CI 0.80-1.15, p=0.66), versus 1.54 (1.17-2.03, p=0.0018) in patients with a raised platelet count (p=0.0027 for interaction). In the per-protocol population, more patients on continuous than on intermittent treatment had grade 3 or worse haematological toxic effects (72 [15%] vs 60 [12%]), whereas nausea and vomiting were more common on intermittent treatment (11 [2%] vs 43 [8%]). Grade 3 or worse peripheral neuropathy (126 [27%] vs 25 [5%]) and hand-foot syndrome (21 [4%] vs 15 [3%]) were more frequent on continuous than on intermittent treatment.InterpretationAlthough this trial did not show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in terms of overall survival, chemotherapy-free intervals remain a treatment option for some patients with advanced colorectal cancer, offering reduced time on chemotherapy, reduced cumulative toxic effects, and improved quality of life. Subgroup analyses suggest that patients with normal baseline platelet counts could gain the benefits of intermittent chemotherapy without detriment in survival, whereas those with raised baseline platelet counts have impaired survival and quality of life with intermittent chemotherapy and should not receive a treatment break.FundingCancer Research UK.
| S-EPMC3159416 | biostudies-literature
Project description:Background and aimChinese herbal injection (CHI) is a widely used preparation for advanced non-small cell lung cancer (NSCLC) treatment to alleviate the adverse drug reactions and enhance the clinical efficacy of chemotherapy. However, its efficacy and safety in combination with platinum-based chemotherapy (PBC) remain poorly understood owing to the lack of high-level evidence in the face of a wide variety of CHIs. Therefore, in this study, we aimed to explore the efficacy and safety of CHIs in combination with PBC regimens in the treatment of mid- and advanced NSCLC.MethodsSystematic evaluation and meta-analysis were conducted as per the Preferred Reporting Project for Systematic Evaluation and Meta-Analysis Protocols (PRISMA-P). Seven databases were comprehensively searched for relevant randomized controlled trials (RCTs) through August 1, 2022. The quality of each study was evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. Statistical analysis was performed using Revman 5.3, with dichotomies expressed as risk ratio (RR) and 95% confidence interval (CI). Objective response rate (ORR) and disease control rate (DCR) were selected as the primary outcomes, with quality of life (QoL) and toxic side effects as secondary outcomes.ResultsA total of 140 RCTs were included in this study. The results of the meta-analysis suggested that, compared with PBC alone, PBC combined with CHIs significantly improved the ORR (RR=1.35, 95% CI: 1.30-1.41, P<0.001), DCR (RR=1.15, 95% CI: 1.13-1.18, P<0.001) and QoL (RR=1.29, 95% CI: 1.24-1.33, P<0.001). Moreover, the combination treatment reduced chemotherapy-induced leukopenia (RR=0.69, 95% CI: 0.64-0.75, P<0.001), anemia (RR=0.70, 95% CI: 0.62-0.79, P<0.001), thrombocytopenia (RR=0.68, 95% CI: 0.62-0.75, P<0.001), nausea and vomiting (RR=0.69, 95% CI: 0.63-0.76, P<0.001), diarrhea (RR=0.59, 95% CI: 0.48-0.73, P<0.001), and constipation (RR=0.68, 95% CI: 0.54-0.86, P=0.001).ConclusionAccording to the available evidence, CHIs in combination with PBC can improve clinical efficacy and reduce the toxic side effects in the treatment of advanced NSCLC. However, considering the study's limitations, more rigorous and high-quality studies are needed to further confirm the results.Systematic review registrationhttps://inplasy.com/inplasy-2022-1-0104/, identifier INPLASY202210104.
| S-EPMC10869539 | biostudies-literature
Project description:BackgroundThe addition of oxaliplatin to adjuvant 5-fluorouracil (5-FU) improves survival of patients with stage III colon cancer in randomized clinical trials (RCTs). However, RCT participants are younger, healthier, and less racially diverse than the general cancer population. Thus, the benefit of oxaliplatin outside RCTs is uncertain.Subjects and methodsPatients younger than 75 years with stage III colon cancer who received chemotherapy within 120 days of surgical resection were identified from five observational data sources-the Surveillance, Epidemiology, and End Results registry linked to Medicare claims (SEER-Medicare), the New York State Cancer Registry (NYSCR) linked to Medicaid and Medicare claims, the National Comprehensive Cancer Network (NCCN) Outcomes Database, and the Cancer Care Outcomes Research & Surveillance Consortium (CanCORS). Overall survival (OS) was compared among patients treated with oxaliplatin vs non-oxaliplatin-containing adjuvant chemotherapy. Overall survival for 4060 patients diagnosed during 2004-2009 was compared with pooled data from five RCTs (the Adjuvant Colon Cancer ENdpoinTs [ACCENT] group, n = 8292). Datasets were juxtaposed but not combined using Kaplan-Meier curves. Covariate and propensity score adjusted proportional hazards models were used to calculate adjusted survival hazard ratios (HR). Stratified analyses examined effect modifiers. All statistical tests were two-sided.ResultsThe survival advantage associated with the addition of oxaliplatin to adjuvant 5-FU was evident across diverse practice settings (3-year OS: RCTs, 86% [n = 1273]; SEER-Medicare, 80% [n = 1152]; CanCORS, 88% [n = 129]; NYSCR-Medicaid, 82% [n = 54]; NYSCR-Medicare, 79% [n = 180]; and NCCN, 86% [n = 438]). A statistically significant improvement in 3-year overall survival was seen in the largest cohort, SEER-Medicare, and in the NYSCR-Medicare cohort (non-oxaliplatin-containing vs oxaliplatin-containing adjuvant therapy, adjusted HR of death: pooled RCTs: HR = 0.80, 95% CI = 0.70 to 0.92, P = .002; SEER-Medicare: HR = 0.70, 95% CI = 0.60 to 0.82, P < .001; NYSCR-Medicare patients aged ?65 years: HR = 0.58, 95% CI = 0.38 to 0.90, P = .02). The association between oxaliplatin treatment and better survival was maintained in older and minority group patients, as well as those with higher comorbidity.ConclusionThe addition of oxaliplatin to 5-FU appears to be associated with better survival among patients receiving adjuvant colon cancer treatment in the community.
| S-EPMC3274510 | biostudies-literature
Project description:What is known and objectiveAn increasing macrolide resistance leads to complex clinical treatment schemes in mycoplasma pneumonia in children. Chinese herbal injection (CHI) is widely used to treat it and may provide a new treatment regimen. This study was conducted to systematically evaluate the efficacy of CHIs combined with azithromycin for treating mycoplasma pneumonia in children by Bayesian network meta-analysis.MethodsRandomized controlled trials (RCTs) of CHIs combined with azithromycin for mycoplasma pneumonia in children were searched in electronic databases and related references from initiation to 30 October 2018. Two researchers conducted data extraction and risk of bias assessment. WinBUGS software and STATA software were adopted to analyse the data.ResultsA total of 167 RCTs were included with 5 CHIs involving 16 144 patients. All CHIs combined with azithromycin had superior effects than azithromycin only among overall outcomes. Yanhuning injection combined with azithromycin ranked highest in four different outcomes and second in two based on surface under the cumulative ranking probabilities (SUCRA). Meanwhile, the results of MD and 95% CIs of concerned outcomes indicated that only Yanhuning injection combined with azithromycin had better response than other CHIs combined with azithromycin. Moreover, cluster analysis results revealed Reduning injection combined with azithromycin was associated with a positive effect on the three group outcomes. Similarly, it was found to be the top three ranking in all outcomes based on SUCRA.What is new and conclusionYanhuning injection combined with azithromycin and Reduning injection combined with azithromycin were found to be preferable treatments based on the data of this study.
| S-EPMC6852301 | biostudies-literature
Project description:BackgroundAlthough the prognostic biomarkers associated with colorectal cancer (CRC) survival are well known, there are limited data on the association between the molecular characteristics and survival after recurrence (SAR). The purpose of this study was to assess the association between pathway mutations and SAR.MethodsOf the 516 patients with stage III or high risk stage II CRC patients treated with surgery and adjuvant chemotherapy, 87 who had distant recurrence were included in the present study. We analyzed the association between SAR and mutations of 40 genes included in the five critical pathways of CRC (WNT, P53, RTK-RAS, TGF-β, and PI3K).ResultsMutation of genes within the WNT, P53, RTK-RAS, TGF-β, and PI3K pathways were shown in 69(79.3%), 60(69.0%), 57(65.5%), 21(24.1%), and 19(21.8%) patients, respectively. Patients with TGF-β pathway mutation were younger and had higher incidence of mucinous adenocarcinoma (MAC) histology and microsatellite instability-high. TGF-β pathway mutation (median SAR of 21.6 vs. 44.4 months, p = 0.021) and MAC (20.0 vs. 44.4 months, p = 0.003) were associated with poor SAR, and receiving curative resection after recurrence was associated with favorable SAR (Not reached vs. 23.6 months, p < 0.001). Mutations in genes within other critical pathways were not associated with SAR. When MAC was excluded as a covariate, multivariate analysis revealed TGF-β pathway mutation and curative resection after distant recurrence as an independent prognostic factor for SAR. The impact of TGF-β pathway mutations were predicted using the PROVEAN, SIFT, and PolyPhen-2. Among 25 mutations, 23(92.0%)-24(96.0%) mutations were predicted to be damaging mutation.ConclusionsMutation in genes within TGF-β pathway may have negative prognostic role for SAR in CRC. Other pathway mutations were not associated with SAR.
| S-EPMC6501409 | biostudies-literature
Project description:BackgroundAlthough treatment of localized anal cancer (AC) is well established, very little evidence is available to inform the management of advanced tumors, and the prognosis of these patients remains poor. We have analyzed treatment pathways and outcomes of a single-institution series of advanced AC patients in order to provide insight into the management of this rare condition.Materials and methodsInclusion criteria included epidermoid histology, inoperable locally recurrent or metastatic disease, and availability of full medical records. The primary objective was overall survival (OS). Prognostic factors were analyzed in univariate models.ResultsSixty-four patients (1997-2014) were included: 16 (25.0%) with inoperable locally advanced and 48 (75.0%) with metastatic tumors. Fifty-one (79.7%) received at least one line of chemotherapy; of these, 37% underwent multimodality treatment. A combination of a platinum agent plus a fluoropyrimidine was the most common first-line regimen (74.5%), with an objective response rate (ORR) of 34.4% (95% confidence interval [CI], 18.6%-53.2%). Paclitaxel-based chemotherapy was used in 15 patients as front-line or salvage treatment, and the overall ORR was 53.3% (95% CI, 26.6%-78.7%). Median progression-free survival (PFS) after first- and second-line chemotherapy was 5.8 (interquartile range [IQR], 2.8-7.6) and 3.2 (IQR, 2.5-7.1) months, respectively. Five-year OS in the overall population was 15% (95% CI, 7.0%-25.0%). Age ≤65 years and liver metastases were predictive of better PFS (hazard ratio [HR], 0.39; 95% CI, 0.16-0.97; p = .04) and worse OS (HR, 2.25; 95% CI, 1.25-4.03; p = .01), respectively.ConclusionA platinum agent plus a fluoropyrimidine and paclitaxel-based chemotherapy are active regimens for advanced AC. Clinical trials are needed to standardize treatment pathways, investigate the potential of novel therapeutics, and improve the poor prognosis of this rare condition. The Oncologist 2017;22:402-408Implications for Practice: Because of the lack of randomized trials, the optimal management of advanced anal cancer is uncertain. Despite its retrospective analysis and relatively small sample size, this is the second largest study ever conducted in this setting, and, as such, it has the potential to serve as a valuable source of information for everyday clinical practice. These findings suggest that chemotherapy with a platinum agent plus a fluoropyrimidine or paclitaxel-containing regimens are reasonable treatment options for patients with inoperable locally recurrent or metastatic anal carcinoma.
| S-EPMC5388368 | biostudies-literature
Project description:ObjectivesFluoropyrimidine-based regimens have been investigated as the second line chemotherapy in patients with advanced pancreatic cancer refractory to gemcitabine. We conducted this systematic review and meta-analysis to evaluate the efficacy and safety profile of fluoropyrimidine combination therapy versus fluoropyrimidine monotherapy in such patients.MethodsThe databases of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ASCO Abstracts and ESMO Abstracts were systematically searched. Randomized controlled trials (RCTs) that compared fluoropyrimidine combination therapy versus fluoropyrimidine monotherapy in patients with gemcitabine-refractory advanced pancreatic cancer were included. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate (ORR) and serious toxicities. Statistical analyses were performed by using Review Manager 5.3. Egger's test was performed to assess the statistical evidence of publication bias by using stata 12.0.ResultsA total of 1183 patients from six randomized controlled trials were included for this analysis. Fluoropyrimidine combination therapy increased ORR [RR 2.82 (1.83-4.33), p<0.00001] and PFS [HR 0.71 (0.62-0.82), p<0.00001], without significant heterogeneity. Fluoropyrimidine combination therapy improved OS [HR 0.82 (0.71-0.94), p = 0.006], with significant heterogeneity (I2 = 76%, p = 0.0009). The significant heterogeneity might have been caused by the different administration regimens and baseline characteristics. Peripheral neuropathy and diarrhea were more common in the regimens containing oxaliplatin and irinotecan, respectively. No publication bias was detected by Egger's tests.ConclusionsCompared with fluoropyrimidine monotherapy, fluoropyrimidine combination therapy had a higher response rate and longer PFS in patients with gemcitabine-refractory advanced pancreatic cancer. Fluoropyrimidine combination therapy could be recommended in the second line setting. However, due to concerns about toxicities, the dose intensities of chemotherapy drugs should be carefully considered in patients with weakness.
| S-EPMC9980826 | biostudies-literature