-
1.
Efficacy and safety of apatinib alone or apatinib plus paclitaxel/docetaxel versus paclitaxel/docetaxel in the treatment of advanced non-small cell lung cancer: A meta-analysis.
Li, Z, Liu, Z, Wu, Y, Li, H, Sun, Z, Han, C, Zhang, X, Zhang, J
Thoracic cancer. 2021;(21):2838-2848
Abstract
BACKGROUND To investigate the efficacy and safety of apatinib alone or apatinib plus paclitaxel/docetaxel versus paclitaxel/docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC) through pooling of open published data. METHODS The electronic databases of Medline (1960-2021.5), Cochrane central register of controlled trials (CENTRAL), EMBASE(1980-2021.5) and Wan fang (1986-2021.5) were systematically searched by two reviewers to identify the relevant clinical trials related to the above subject. The objective response rate (ORR), disease control rate (DCR) and drug relevant adverse reactions were pooled and demonstrated by risk ratio (RR) and 95% confidence interval (95% CI). The statistical heterogeneity across studies was assessed by I-square test. The publication bias was evaluated by Egger's line regression test and demonstrated by Begg's funnel plot. RESULTS Eleven prospective studies were included in the meta-analysis. The pooled results indicated that the ORR (RR = 1.62, 95% CI: 1.32-2.00, p < 0.05) and DCR (RR = 1.29, 95% CI: 1.18-1.41, p < 0.05) of apatinib alone or apatinib plus paclitaxel/docetaxel was significantly higher than that of the paclitaxel/docetaxel group for advanced NSCLC, respectively. The drug-related adverse reaction was not statistically different between apatinib alone or apatinib plus paclitaxel/docetaxel with regard to the hand-foot syndrome, gastrointestinal reaction, thrombocytopenia, anemia and leukocytopenia (pall > 0.05) except for hypertension (RR = 3.60, 95% CI: 1.26-10.31, p < 0.05). Subgroup analysis also indicated that the hypertension and hand-foot syndrome in apatinib + paclitaxel/docetaxel were higher than that of the paclitaxel/docetaxel group with a statistical difference (p < 0.05). CONCLUSIONS Apatinib alone or apatinib plus paclitaxel/docetaxel was superior to paclitaxel/docetaxel for ORR and DCR. However, combined treatment with apatinib appears to increase the risk of a patient developing an adverse reaction, especially hypertension and hand-foot syndrome.
-
2.
Comparative efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy for active rheumatoid arthritis.
Ho Lee, Y, Gyu Song, G
Journal of clinical pharmacy and therapeutics. 2020;(4):674-681
Abstract
WHAT IS KNOWN AND OBJECTIVE Several clinical trials have attempted to evaluate the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy in patients with active rheumatoid arthritis (RA), but their relative efficacy and safety as monotherapy remain unclear due to the lack of data from head-to-head comparison trials. The relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy for rheumatoid arthritis (RA) were assessed. METHODS We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) and examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy relative to placebo in patients with RA. RESULTS AND DISCUSSION Five RCTs comprising 1547 patients met the inclusion criteria. Compared with placebo, tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy showed a significantly higher American College of Rheumatology 20% (ACR20) response rate. Peficitinib 150 mg monotherapy showed the highest ACR20 response rate (odds ratio, 17.24.39; 95% credible interval, 6.57-51.80). The ranking probability based on the surface under the cumulative ranking curve indicated that peficitinib 150 mg had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by peficitinib 100 mg, filgotinib 200 mg, filgotinib 100 mg, tofacitinib 5 mg, upadacitinib 15 mg, baricitinib 4 mg and placebo. However, the number of patients who experienced serious adverse events did not differ significantly between the JAK inhibitors, except for tofacitinib 5 mg, and placebo. WHAT IS NEW AND CONCLUSION All five JAK inhibitors-tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib-were efficacious monotherapy interventions for active RA, and differences were noted in their efficacy and safety in monotherapy.
-
3.
Cerivastatin for lowering lipids.
Adams, SP, Tiellet, N, Alaeiilkhchi, N, Wright, JM
The Cochrane database of systematic reviews. 2020;(1):CD012501
-
-
Free full text
-
Abstract
BACKGROUND Cerivastatin was the most potent statin until it was withdrawn from the market due to a number of fatalities due to rhabdomyolysis, however, the dose-related magnitude of effect of cerivastatin on blood lipids is not known. OBJECTIVES Primary objective To quantify the effects of various doses of cerivastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in children and adults with and without cardiovascular disease. The aim of this review is to examine the pharmacology of cerivastatin by characterizing the dose-related effect and variability of the effect of cerivastatin on surrogate markers. Secondary objectives To quantify the effect of various doses of cerivastatin compared to placebo on withdrawals due to adverse effects. To compare the relative potency of cerivastatin with respect to fluvastatin, atorvastatin and rosuvastatin for LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides. SEARCH METHODS The Cochrane Hypertension Information Specialist searched the following databases for RCTs up to March 2019: CENTRAL (2019, Issue 3), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov.We also searched the European Patent Office, FDA.gov, and ProQuest Dissertations & Theses, and contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA RCTs and controlled before-and-after studies evaluating the dose response of different fixed doses of cerivastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease. DATA COLLECTION AND ANALYSIS Two review authors independently assessed eligibility criteria for trials to be included and extracted data. We entered data from RCTs and controlled before-and-after studies into Review Manager 5 as continuous and generic inverse variance data respectively. We collected information on withdrawals due to adverse effects from the RCTs. We assessed all trials using the 'Risk of bias' tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases. MAIN RESULTS Fifty trials (19 RCTs and 31 before-and-after studies) evaluated the dose-related efficacy of cerivastatin in 12,877 participants who had their LDL cholesterol measured. The participants were of any age with and without cardiovascular disease and the trials studied cerivastatin effects within a treatment period of three to 12 weeks. Cerivastatin 0.025 mg/day to 0.8 mg/day caused LDL cholesterol decreases of 11.0% to 40.8%, total cholesterol decreases of 8.0% to 28.8% and triglyceride decreases of 9.0% to 21.4%. We judged the certainty of evidence for these effects to be high. Log dose-response data over doses of 2.5 mg to 80 mg revealed strong linear dose-related effects on LDL cholesterol, total cholesterol and triglycerides. When compared to fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250-fold more potent than fluvastatin, 20-fold more potent than atorvastatin and 5.5-fold more potent than rosuvastatin at reducing LDL cholesterol; 233-fold more potent than fluvastatin, 18-fold more potent than atorvastatin and six-fold more potent than rosuvastatin at reducing total cholesterol; and 125-fold more potent than fluvastatin, 11-fold more potent than atorvastatin and 13-fold more potent than rosuvastatin at reducing triglycerides. There was no dose-related effect of cerivastatin on HDL cholesterol, but overall cerivastatin increased HDL cholesterol by 5%. There was a high risk of bias for the outcome withdrawals due to adverse effects, but a low risk of bias for the lipid measurements. Withdrawals due to adverse effects were not different between cerivastatin and placebo in 11 of 19 of these short-term trials (risk ratio 1.09, 95% confidence interval 0.68 to 1.74). AUTHORS' CONCLUSIONS The LDL cholesterol, total cholesterol, and triglyceride lowering effect of cerivastatin was linearly dependent on dose. Cerivastatin log dose-response data were linear over the commonly prescribed dose range. Based on an informal comparison with fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250-fold more potent than fluvastatin, 20-fold more potent than atorvastatin and 5.5-fold more potent than rosuvastatin in reducing LDL cholesterol, and 233-fold greater potency than fluvastatin, 18-fold greater potency than atorvastatin and six-fold greater potency than rosuvastatin at reducing total cholesterol. This review did not provide a good estimate of the incidence of harms associated with cerivastatin because of the short duration of the trials and the lack of reporting of adverse effects in 42% of the RCTs.
-
4.
Safety and efficacy of vorapaxar in secondary prevention of atherosclerotic disease: A meta-analysis of randomized control trials.
Sharma, A, Helft, G, Garg, A, Agrawal, S, Chatterjee, S, Lavie, CJ, Goel, S, Mukherjee, D, Marmur, JD
International journal of cardiology. 2017;:617-624
Abstract
OBJECTIVE To study the cumulative evidence for vorapaxar use in patients with atherosclerotic cardiovascular disease. METHODS A systematic review of randomized control trials in MEDLINE, EMBASE, EBSCO, CINAHL, Web of Science and Cochrane databases comparing vorapaxar with placebo was performed. Pre-specified efficacy endpoints were all-cause mortality, CV mortality, myocardial infarction (MI), ischemic stroke and repeat revascularization. The pre-specified safety endpoint was intracranial hemorrhage (ICH) and a composite of TIMI major and minor bleeding. Risk ratios were used as the metric of choice by applying random effects models. RESULTS Five randomized controlled trials with 40,630 patients were included in final analysis. Compared with placebo, vorapaxar led to a statistically non-significant reduction in risk of MI [RR 0.86; 95% CI 0.80-0.93, p=0.427] and ischemic stroke [RR 0.84; 95% CI 0.72-0.97, p=0.920]. No differences were observed between vorapaxar and placebo with respect to all-cause mortality [RR 0.99; 95% CI 0.90-1.08, p=0.620], cardiovascular mortality [RR 0.94; 95% CI 0.83-1.06, p=0.351], repeat revascularization [RR 0.97; 95% CI 0.82-1.15, p=0.236], and TIMI bleeding [RR 1.29; 95% CI 0.98-1.69, p=0.126]. Vorapaxar was associated with a statistically non-significant higher risk of ICH [RR 2.36; 95% CI 1.40-3.96, p=0.137] compared with placebo. CONCLUSION Addition of Vorapaxar to standard medical therapy in in patients with atherosclerotic disease led to a statistically non-significant reduction in the risk of MI and ischemic stroke at the cost of statistically non-significant increase in risk of ICH.
-
5.
Meta-analysis of dermatological toxicities associated with sorafenib.
Zhang, L, Zhou, Q, Ma, L, Wu, Z, Wang, Y
Clinical and experimental dermatology. 2011;(4):344-50
Abstract
A meta-analysis was performed to determine the type, incidence and risks of dermatological toxicities associated with the multikinase inhibitor sorafenib. A literature search was performed using the electronic databases PubMed and EMBASE, and conference abstracts published by the American Society of Clinical Oncology. Eligible studies included prospective phase II or III clinical trials, and expanded-access programmes (i.e. outside a clinical trial) of patients with solid tumours assigned sorafenib at a starting dose of 400 mg twice daily. The overall incidences and risk ratios of dermatological toxicities associated with sorafenib were analysed. For patients assigned sorafenib, the overall incidence of all-grade rash/desquamation was 35.4% (95% CI 0.29-0.43), hand-foot skin reaction (HFSR) 39.0% (95% CI 0.32-0.47), alopecia 25.5% (95% CI 0.18-0.35), pruritus 14.0% (95% CI 0.10-0.20) and dry skin 14.1% (95% CI 0.10-0.20). High-grade rash/desquamation events occurred in 5.0% (95% CI 0.04-0.07), HFSR in 9.0% (95% CI 0.082-0.098), alopecia in 4/1793, pruritus in 2/1265 and dry skin in 0/1689 of patients assigned sorafenib. Meta-analysis of risk ratio showed that sorafenib was associated with a significantly increased risk of rash/desquamation [risk ratio (RR) 2.73; 95% CI 1.66-4.49)], HFSR (RR 7.50; 95% CI 3.90-14.40) and alopecia (RR 7.55; 95% CI 5.26-10.84) in patients with solid tumours, but risk of pruritus (RR 1.80; 95% CI 0.77-4.22) or dry skin (RR 2.18; 95% CI 0.88-5.40) was not increased. In conclusion, the most frequent dermatological toxicities associated with sorafenib were HFSR, rash/desquamation, alopecia, pruritus and dry skin. There was a significantly increased risk of HFSR, rash/desquamation and alopecia with sorafenib compared with placebo. Skin toxicities were mainly mild or moderate in severity. Appropriate prevention and management are recommended.
-
6.
Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials.
Je, Y, Schutz, FA, Choueiri, TK
The Lancet. Oncology. 2009;(10):967-74
Abstract
BACKGROUND Sunitinib and sorafenib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine-kinase inhibitors used in various cancers. Bleeding has been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to calculate the incidence and relative risk associated with use of sunitinib and sorafenib. METHODS We searched PubMed (from January, 1966, to April, 2009) and meeting proceedings of the American Society of Clinical Oncology and the European Society of Medical Oncology (2004-09) for relevant clinical trials. Eligible studies included phase 2 and 3 trials and expanded-access programmes. Statistical analyses were done to calculate summary incidences, relative risks, and 95% CI, using random-effects or fixed-effects models based on the heterogeneity of included studies. FINDINGS 23 trials were selected for the meta-analysis, yielding a total of 6779 patients. The incidence of bleeding events (all grades) was 16.7% (95% CI 12.7-21.5), and that of high-grade events was 2.4% (1.6-3.9). The relative risk of all-grade bleeding events associated with sunitinib and sorafenib (for randomised controlled trials only) was 2.0 (1.14-3.49; p=0.015). Our analysis was also stratified by underlying malignant disease (renal-cell carcinoma vs non-renal-cell carcinoma) and agent used, but no differences were recorded. INTERPRETATION Treatment with the VEGFR tyrosine-kinase inhibitors sunitinib and sorafenib is associated with a significant increase in risk of bleeding. FUNDING None.
-
7.
Risk of hand-foot skin reaction with sorafenib: a systematic review and meta-analysis.
Chu, D, Lacouture, ME, Fillos, T, Wu, S
Acta oncologica (Stockholm, Sweden). 2008;(2):176-86
Abstract
BACKGROUND Hand-foot skin reaction (HFSR) is a dose-limiting toxicity associated with sorafenib, an oral multi-kinase inhibitor with clinical activity against solid tumors. This study was conducted to determine the risk of developing HFSR among patients receiving sorafenib. PATIENTS AND METHODS Databases from Pubmed, Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through July, 2007 were searched to identify relevant studies. Eligible studies were prospective clinical trials using single agent sorafenib. The summary incidence rate and the relative risk (RR) were calculated using random-effects model. RESULTS A total of 4 883 patients in 11 trials with metastatic tumors were included for analysis. Among patients receiving sorafenib, the summary incidence of all-grade HFSR was 33.8% (95% CI: 24.5-44.7%) with significant difference between patients with RCC and non-RCC malignancy (RR 1.52, 95% CI: 1.32-1.75%, p<0.001). The incidence of high-grade HFSR was 8.9% (95% CI: 7.3-10.7%). In addition, sorafenib was associated with a significant increased risk of HFSR with RR of 6.6 (95% CI: 3.7 to 11.7, p<0.001) in comparison with controls. CONCLUSION There is a significant risk of HFSR associated with sorafenib. Proper management and further study are recommended to reduce the risk.
-
8.
Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis.
Wu, S, Chen, JJ, Kudelka, A, Lu, J, Zhu, X
The Lancet. Oncology. 2008;(2):117-23
Abstract
BACKGROUND Sorafenib is used in patients with advanced renal-cell carcinoma (RCC) or hepatocellular cancer, and its application in other types of cancers is also undergoing extensive clinical assessment. Hypertension is one of the major side-effects of this drug, and reported incidences vary substantially between clinical trials. We did a systematic review and meta-analysis of published clinical trials to establish the incidence of hypertension associated with sorafenib. The aim of this study is to gain a better understanding of the overall risk of hypertension in patients with cancer who receive sorafenib. METHODS Databases, including Medline (July, 1966, to July, 2007), and Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 to 2007 were searched to identify relevant studies. Eligible studies were prospective clinical trials of patients with cancer assigned single-drug sorafenib at 400 mg twice daily with data on hypertension available. Incidence and relative risk (RR) of hypertension were calculated using a random-effects or fixed-effects model, depending on the heterogeneity of the included studies. FINDINGS Nine studies published between January, 2006, and July, 2007, which included a total of 4599 patients with RCC or other solid tumours, were selected from 223 articles screened for analysis. For patients assigned sorafenib, the overall incidence of all-grade and high-grade (ie, grade 3 or 4) hypertension were 23.4% (95% CI 16.0-32.9%) and 5.7% (2.5-12.6%), respectively. No significant difference was noted between patients with RCC or a non-RCC malignancy (all grade: RR 1.03 [95% CI 0.73-1.45], p=0.89; high-grade: RR 1.23 [0.76-1.99], p=0.40) who were assigned sorafenib. Sorafenib was associated with a significantly increased risk of all-grade hypertension in patients with cancer with an RR of 6.11 (2.44-15.32], p<0.001) compared with controls. INTERPRETATION Patients with cancer assigned sorafenib have a significant risk of developing hypertension. Appropriate monitoring and treatment is strongly recommended to prevent cardiovascular complications.