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Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials.

ABSTRACT: Osteosarcoma is the most common malignant bone tumour. Due to the high metastasis rate and drug resistance of this disease, multi-drug regimens are necessary to control tumour cells at various stages of the cell cycle, eliminate local or distant micrometastases, and reduce the emergence of drug-resistant cells. Many adjuvant chemotherapy protocols have shown different efficacies and controversial results. Therefore, we classified the types of drugs used for adjuvant chemotherapy and evaluated the differences between single- and multi-drug chemotherapy regimens using network meta-analysis.We searched electronic databases, including PubMed (MEDLINE), EmBase, and the Cochrane Library, through November 2016 using the keywords "osteosarcoma", "osteogenic sarcoma", "chemotherapy", and "random*" without language restrictions. The major outcome in the present analysis was progression-free survival (PFS), and the secondary outcome was overall survival (OS). We used a random effect network meta-analysis for mixed multiple treatment comparisons.We included 23 articles assessing a total of 5742 patients in the present systematic review. The analysis of PFS indicated that the T12 protocol (including adriamycin, bleomycin, cyclophosphamide, dactinomycin, methotrexate, cisplatin) plays a more critical role in osteosarcoma treatment (surface under the cumulative ranking (SUCRA) probability 76.9%), with a better effect on prolonging the PFS of patients when combined with ifosfamide (94.1%) or vincristine (81.9%). For the analysis of OS, we separated the regimens to two groups, reflecting the disconnection. The T12 protocol plus vincristine (94.7%) or the removal of cisplatinum (89.4%) is most likely the best regimen.We concluded that multi-drug regimens have a better effect on prolonging the PFS and OS of osteosarcoma patients, and the T12 protocol has a better effect on prolonging the PFS of osteosarcoma patients, particularly in combination with ifosfamide or vincristine. The OS analysis showed that the T12 protocol plus vincristine or the T12 protocol with the removal of cisplatinum might be a better regimen for improving the OS of patients. However, well-designed randomized controlled trials of chemotherapeutic protocols are still necessary.

SUBMITTER: Wang X

PROVIDER: S-EPMC5372345 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials.

Wang Xiaojie X Zheng Hong H Shou Tao T Tang Chunming C Miao Kun K Wang Ping P

Journal of orthopaedic surgery and research 20170329 1

<h4>Background</h4>Osteosarcoma is the most common malignant bone tumour. Due to the high metastasis rate and drug resistance of this disease, multi-drug regimens are necessary to control tumour cells at various stages of the cell cycle, eliminate local or distant micrometastases, and reduce the emergence of drug-resistant cells. Many adjuvant chemotherapy protocols have shown different efficacies and controversial results. Therefore, we classified the types of drugs used for adjuvant chemothera ...[more]

PMID: 28356114

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Project description:Different adjuvant chemotherapy regimens are available for early-stage breast cancer. Because conventional meta-analysis does not allow comparing all regimens, we performed a network meta-analysis to identify the most effective adjuvant chemotherapy regimen.To find the most effective adjuvant therapy regimen for early-stage breast cancer.We searched MEDLINE, Embase, and the Cochrane Library for articles published before June 2015; the American Society of Clinical Oncology annual meeting abstracts from January 1983 through December 2014; and the American Association for Cancer Research annual meeting abstracts from January 1916 through December 2014. Additionally, we manually searched bibliographies for related references.We included randomized clinical trials of adjuvant treatments for early-stage breast cancer that compared 2 or more of the following: no adjuvant chemotherapy; sequential anthracycline-cyclophosphamide and taxane (AC-T); concurrent anthracycline-cyclophosphamide and taxane (ACT); anthracycline-cyclophosphamide without taxane (AC); docetaxel and cyclophosphamide (TC); cyclophosphamide, methotrexate, and fluorouracil (CMF); and platinum-containing regimens.We followed the PRISMA guidelines. Two investigators independently selected the articles and extracted information. Disagreements were resolved by discussion with another author. Quality was assessed by Cochrane risk-of-bias method. Data were pooled using random-effects models.We used network meta-analysis to test the most effective adjuvant therapy regimen in terms of overall survival (OS) by comparing regimens listed in the National Comprehensive Cancer Network guidelines and platinum-containing regimens.We identified 24 trials. The TC and platinum-containing regimens had OS benefit similar to that of sequential AC-T (TC hazard ratio [HR], 0.93; 95% CI, 0.62-1.40; and platinum HR, 0.93; 95% CI, 0.66-1.31). Patients treated with CMF or AC had significantly worse OS than those treated with sequential AC-T (CMF HR, 1.56; 95% CI, 1.32-1.85; and AC HR, 1.22; 95% CI, 1.10-1.37). Platinum-containing regimens tended to be more toxic than sequential AC-T. The toxicity of TC was similar to or less than that of sequential AC-T. Meta-regression analysis showed that hormone receptor status did not impact the HRs for OS for any regimen.Sequential AC-T is likely to be the most effective adjuvant therapy regimen for early-stage breast cancer regardless of hormone receptor status.

Project description:BackgroundChemotherapy-induced peripheral neurotoxicity (CIPN) is the most common adverse effect in patients undergoing chemotherapy, and no effective interventions are currently available for its prevention and treatment. Non-pharmacological therapies appear to be beneficial for the prevention and treatment of CIPN, but it remains unclear which therapy is most effective. The aim of this study was to identify the most effective non-pharmacological therapy for CIPN patients.MethodsPubMed, Web of Science, Embase, and Cochrane Library were searched for randomized controlled trials on non-pharmacological therapies for CIPN. The primary outcomes included pain and peripheral neuropathological symptoms, and the secondary outcomes included quality of life, sensory and motor symptoms. The pairwise analysis and a network meta-analysis were performed using a random effects model.ResultsA total of 46 articles were included in this study, involving 2,878 participants. Our study showed that massage was more effective in pain-alleviating compared with acupuncture [SMD = 0.81, 95%CI (0.04, 1.57)], vitamin and gabapentin [SMD = 2.56, 95%CI (1.39, 3.74)], and usual care and placebo [SMD = 0.9, 95%CI (0.31, 1.49)]. As for attenuating peripheral neuropathological symptoms, massage was more effective than usual care and placebo [SMD = 0.75, 95%CI (0.33, 1.17)], sensorimotor training [SMD = 1.17, 95%CI (0.24, 2.10)], electrostimulation [SMD=-1.18, 95%CI (-2.14, -0.21)], multimodal exercise [SMD=-0.82, 95%CI (-1.57, -0.08)], and resistance training [SMD = 1.03, 95%CI (0.11, 1.95)]. Massage was also more effective than other non-pharmacological therapies in improving quality of life, sensory and motor symptoms.ConclusionsAccording to our study, massage has advantages in alleviating pain, improving quality of life, and improving peripheral neuropathological symptoms and has better effect than other non-pharmacological interventions, representing certain clinical significance. However, the results of this study should be interpreted with caution due to the limitations of the included studies. In the future, more high-quality multi arm randomized controlled trials can be attempted to provide direct comparisons of the relative effects of non-pharmacological interventions.

Project description:BackgroundInduction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) for non-metastatic locoregionally advanced nasopharyngeal carcinoma (NPC) has gained considerable attention. However, the most efficacious IC regimens remain investigational. We aimed to compare the survival benefits of all available IC regimens followed by CCRT in this network meta-analysis.MethodsAll randomized-controlled trials of CCRT with or without IC in non-metastatic locoregionally advanced NPC were included, with an overall nine trials of 2,705 patients counted in the analysis. CCRT alone was the reference category. Eight IC regimens followed by CCRT were analyzed: docetaxel + cisplatin (DC), gemcitabine + carboplatin + paclitaxel (GCP), gemcitabine + cisplatin (GP), mitomycin + epirubicin + cisplatin + fluorouracil + leucovorin (MEPFL), cisplatin + epirubicin + paclitaxel (PET), cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX) and cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX). Fixed-effects frequentist network meta-analysis models was applied and P-score was used to rank the treatments.ResultsDC, GP, and PX were the top three IC regimens with the highest probability of benefit on overall survival (OS). Their corresponding hazard ratios (HRs) (95% CIs) compared with CCRT alone were of 0.24 (0.08-0.73), 0.43 (0.24-0.77), and 0.54 (0.27-1.09) and the respective P-scores were 94%, 82%, and 68%. The first three IC regimens showing significantly improved progression-free survival (PFS) were PX, followed by GP and DC with respective HRs of 0.46 (0.24-0.88), 0.51 (0.34-0.77), and 0.49 (0.20-1.20), and P-scores of 82%, 78%, and 74%. Among the studies in the intensity-modulated radiation therapy (IMRT) era, GP and PX were the best performed IC regimens, whilst DC performed the best among non-IMRT studies. Doublet and gemcitabine-based IC regimens had better survival benefits compared to triplet and taxane-based IC regimens, respectively.ConclusionsGiven its consistent superiority in both OS and PFS, DC, GP, and PX ranked among the three most efficacious IC regimens in both the overall and subgroup analysis of IMRT or non-IMRT studies. Exploratory analyses suggested that doublet and gemcitabine-based IC regimens showed better survival performance.

Project description:ObjectivesAlthough many trials have assessed the effect of acupuncture on knee osteoarthritis (KOA), its efficacy remains controversial. Sham acupuncture techniques are regarded as representative control interventions in acupuncture trials and sometimes incorporate the use of sham devices (base units) to support a non-penetrating needle. To achieve successful blinding, these trials also use acupuncture base units in the verum acupuncture group. Base units are not used in real-world clinical settings. We aimed to assess the effect sizes of verum and sham acupuncture for KOA in sham-controlled trials with or without base units.MethodsA total of 10 electronic databases for randomized controlled trials (RCTs) comparing the efficacy of verum manual acupuncture and sham acupuncture for the treatment of KOA were searched for articles published before April 12, 2022. The primary outcome was pain intensity, and the secondary outcomes included physical function. The first assessment after the end of treatment was chosen for analysis. Effect sizes are reported as standardized mean differences (SMDs) with 95% confidence intervals (95% CIs). The risk of bias was assessed using the Cochrane risk of bias tool, and publication bias was evaluated using a funnel plot and Egger's test. The quality of evidence for estimates was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach.ResultsFifteen RCTs were included. There was generally a low risk of bias except for the difficulty in blinding acupuncture therapists (performance bias). Compared to verum acupuncture in sham-controlled trials using base units, verum acupuncture in sham-controlled trials without base units was more effective for improving pain (SMD -0.56, 95% CI -1.09 to -0.03) and function (SMD -0.73, 95% CI -1.36 to -0.10) in KOA. The quality of evidence for network estimates was moderate to low due to the risk of bias and imprecision.ConclusionThese findings suggest that verum acupuncture in different types of sham-controlled trials has different effect sizes for KOA. Because base units are not used in clinical settings, the results of verum acupuncture in sham-controlled trials with base units need to be interpreted carefully.Systematic review registrationhttps://www.researchregistry.com/browse-the-registry#registryofsystematicreviewsmeta-analyses/registryofsystematicreviewsmeta-analysesdetails/6269f962606c5e001fd8790c/, identifier reviewregistry1351.

Project description:Background: Hyperuricemia is very common in patients with chronic kidney disease (CKD); the role of hyperuricemia in the occurrence and progression of kidney disease remains an interesting and unresolved issue for nephrologists, and whether urate-lowering therapy (ULT) is warranted in CKD patients is still in controversy. To summarize and compare the clinical outcomes and adverse events (AEs) of three common ULT drugs, we performed a systematic review and network meta-analysis of randomized clinical trials (RCTs). Method: PubMed, MEDLINE, Clinical Trials.gov, EMBASE, and the Cochrane Central Register of Controlled Trials electronic databases were searched. The network meta-analysis was performed using the "gemtc 0.8-7" and its dependent packages in R software. The primary outcome was the change of renal function and uric acid; creatinine, proteinuria, blood pressure, and adverse events were assessed as the secondary outcomes. Results: 16 RCTs involving 1,943 patients were included in the final network analysis. Febuxostat, allopurinol, and benzbromarone were not found to exert superior effects over placebo upon renoprotective effect. With respect to lowering urate, the three drugs showed to be statistically superior to placebo, while febuxostat could better lower urate than allopurinol (MD: -1.547; 95% CrI: -2.473 to -0.626). It is also indicated that febuxostat was superior to placebo at controlling blood pressure, while no differences were observed when allopurinol and benzbromarone were compared to placebo. These results are stable in subgroup analysis. Conclusion: There is insufficient evidence to support the renoprotective effects of the three urate-lowering agents in CKD patients with hyperuricemia; febuxostat shows a tendency to be superior to allopurinol on lowering the decline of eGFR and increment of proteinturia, but the difference does not reach a statistical significance. Regarding its urate-lowering effect, febuxostat appears to be a satisfactory alternative to allopurinol and benzbromarone, and can control blood pressure better.

Project description:BackgroundVarious enhanced patient instructions (EPIs) have been used for bowel preparation (BP) and our previous meta-analysis also demonstrated the efficacy of EPIs in increasing the colonic polyp and adenoma detection rates; however, the optimal method for adequate BP has not yet been developed.ObjectiveWe performed a network meta-analysis to determine the optimal instructions.MethodsWe searched for randomized controlled trials (RCTs) comparing the effectiveness of EPIs with each other or standard patient instructions (SPIs) for BP. We performed direct and Bayesian network meta-analyses for all instructions and used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria to appraise the quality of evidence.ResultsWe included 23 RCTs (7969 patients) comparing 10 different instructions. In direct meta-analyses, most of the EPIs, except visual aids and mobile apps, increased the adequate preparation rate (APR). Network meta-analyses showed that additional explanations were superior to visual aids (odds ratio [OR] 0.35, 95% CI 0.19-0.59), telephone calls (OR 0.62, 95% CI 0.37-0.99), educational videos (OR 0.79, 95% CI 0.5-0.77), and mobile apps (OR 0.33, 95% CI 0.14-0.68) with low-to-high-quality evidence; newly designed booklets (OR 3.28, 95% CI 1.59-6.16), SMS text messaging (OR 2.33, 95% CI 1.28-3.91), telephone calls (OR 1.86, 95% CI 1.03-1.78), educational videos (OR 2.33, 95% CI 1.40-3.65), and social media applications (OR 2.42, 95% CI 1.4-3.93) were superior to visual aids and mobile apps with low-to-high-quality evidence. SMS text messaging, telephone calls, and social media applications increase adherence to and satisfaction with the BP regime. Social media applications reduce the risk of adverse events (AEs). Telephone calls and social media applications increase the polyp detection rate (PDR).ConclusionsNewly designed booklets, telephone calls, educational videos, and social media applications can improve the quality of BP. Telephone calls and social media applications improve adherence to and satisfaction with the BP regime, reduce the risk of AEs, and increase the PDR.Trial registrationINPLASY (International Platform of Registered Systematic Review and Meta-analysis Protocols) INPLASY2020120103; https://inplasy.com/inplasy-2020-12-0103/.

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Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials.

Publications

Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials.

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