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Medicine Aug 2020Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the primary treatment in treating with EGFR mutant nonsmall cell lung cancer (NSCLC). This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the primary treatment in treating with EGFR mutant nonsmall cell lung cancer (NSCLC). This systematic review and meta-analysis aimed to evaluate the efficacy and safety of the third-generation EGFR-TKI, osimertinib, and summarize the risk factors associating with outcome after osimertinib treatment.
METHOD
The Ovid Medline, Embase, Cochrane Library, and Pubmed were systematically searched due to December 10, 2019. All the studies that mentioned the overall survival (OS), progression-free survival (PFS), treatment response, and adverse events (AEs) of osimertinib were involved in our study. Hazard ratio (HR) with 95% confidence intervals was used for comparing OS and PFS.
RESULT
A total of 47 studies were included in the systematic review, of which 14 studies were used to compare the efficacy between osimertinib and other EGFR-TKI or chemotherapy. Patients treating with osimertinib favors a higher OS and PFS in all the patients (HR = 0.56 and 0.38, P < .001, respectively), and in subgroup analysis, compared with other treatments. Median 55% T790 mutant NSCLC patients might experience partial response, and 25% of patients remained as stable disease. The incidence of severe AE ranged from 0% to 5%, and the most common severe AE was pneumonia (3%). Patients with the T858R mutation may have a better OS than Del 19 mutation (HR = 0.55, P = .037), while patients who have a smoking history may have a higher risk of progression than never-smoker patients (HR = 1.47, P = .028).
CONCLUSION
Osimertinib has an impressive antitumor activity compared with prior EGFR-TKI and chemotherapy with an acceptable response and tolerable AEs. EGFR mutation type and smoking status were the risk factors for mortality and progression in NSCLC patients.
Topics: Acrylamides; Aniline Compounds; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cigarette Smoking; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Pneumonia; Progression-Free Survival; Survival Rate
PubMed: 32846826
DOI: 10.1097/MD.0000000000021826 -
Molecular Biology Reports Dec 2022L-asparaginases are mostly obtained from bacterial sources for their application in the therapy and food industry. Bacterial L-asparaginases are employed in the...
L-asparaginases are mostly obtained from bacterial sources for their application in the therapy and food industry. Bacterial L-asparaginases are employed in the treatment of Acute Lymphoblastic Leukemia (ALL) and its subtypes, a type of blood and bone marrow cancer that results in the overproduction of immature blood cells. It also plays a role in the food industry in reducing the acrylamide formed during baking, roasting, and frying starchy foods. This importance of the enzyme makes it to be of constant interest to the researchers to isolate novel sources. Presently L-asparaginases from E. coli native and PEGylated form, Dickeya chrysanthemi (Erwinia chrysanthemi) are in the treatment regime. In therapy, the intrinsic glutaminase activity of the enzyme is a major drawback as the patients in treatment experience side effects like fever, skin rashes, anaphylaxis, pancreatitis, steatosis in the liver, and many complications. Its significance in the food industry in mitigating acrylamide is also a major reason. Acrylamide, a potent carcinogen was formed when treating starchy foods at higher temperatures. Acrylamide content in food was analyzed and pre-treatment was considered a valuable option. Immobilization of the enzyme is an advancing and promising technique in the effective delivery of the enzyme than in free form. The concept of machine learning by employing the Artificial Network and Genetic Algorithm has paved the way to optimize the production of L-asparaginase from its sources. Gene-editing tools are gaining momentum in the study of several diseases and this review focuses on the CRISPR-Cas9 gene-editing tool in ALL.
Topics: Humans; Acrylamide; Asparaginase; Dickeya chrysanthemi; Escherichia coli; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 35816224
DOI: 10.1007/s11033-022-07688-4 -
Annals of Palliative Medicine Feb 2021Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been approved by the U.S. Food and Drug Administration in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been approved by the U.S. Food and Drug Administration in treating T790M mutationpositive advanced non-small cell lung cancer (NSCLC). A systematic review and meta-analysis was conducted to assess the efficacy and safety of osimertinib in treating advanced NSCLC patients with acquired T790M mutation.
METHODS
PubMed, EMBASE, Cochrane Library and Web of Science were searched to obtain the eligible studies following the "population, interventions, comparisons, outcomes, study design" (PICOS) criteria. The pooled analysis of objective response rate (ORR), disease controlled rate (DCR), progressionfree survival (PFS), overall survival (OS) and adverse events (AEs) were performed using STATA12.0 and RevMan5.0.
RESULTS
A total of 1,050 patients were included in the meta-analysis. The combined osimertinib ORR was 0.64 (95% CI, 0.60-0.69), the ORR of central nervous system (CNS) was 0.54 (95% CI, 0.37-0.71), DCR was 0.89 (95% CI, 0.86-0.92), PFS at six months (PFS-6m) rate was 0.69 (95% CI, 0.58-0.79), PFS at one year (PFS-1y) rate was 0.33 (95% CI, 0.20-0.46), OS at one year (OS-1y) rate was 0.69 (95% CI, 0.55-0.84). The pooled incidence rate of the AEs of grade ≥ III was 0.25 (95% CI, 0.09-0.40). The results from Begg's and Egger's tests presented no publication bias in the included studies.
CONCLUSIONS
Osimertinib demonstrated a superior therapeutic benefit with high efficacy and low toxicity for T790M-positive advanced NSCLC patients who were treated with early-generation EGFR-TKIs. Meanwhile, osimertinib showed promising for the treatment of advanced patients with CNS metastases.
Topics: Acrylamides; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors
PubMed: 33474947
DOI: 10.21037/apm-20-1357 -
BMC Cancer Jul 2020Between 30 and 50% of colon tumors have mutations in the Kirsten-ras (KRAS) gene, which have a large nutritional attributable risk. Despite its high frequency in...
BACKGROUND
Between 30 and 50% of colon tumors have mutations in the Kirsten-ras (KRAS) gene, which have a large nutritional attributable risk. Despite its high frequency in colorectal cancer (CRC), data to support specific associations between KRAS mutations in CRC and diet are sparse. Here, we conducted a systematic review to summarize the current epidemiological evidence on the association between various dietary factors and KRAS mutations.
METHODS
PubMed, Science Direct, and Cochrane databases were searched for relevant studies published until December 31, 2019, using inclusion and exclusion criteria in accordance with PRISMA guidelines. We analyzed the studies to find associations between nutritional factors and CRC tumors with KRAS mutations in humans.
RESULTS
We identified 28 relevant studies to include in this systematic review. In-depth analyses showed unclear associations between nutritional factors and KRAS mutations in CRC. Most epidemiological studies in the same nutrient or food often reported conflicting and/or inconclusive findings, whereas for some dietary factors, the results were homogeneous.
CONCLUSIONS
Further research using a more robust prospective cohort study is needed to lend more credence to the epidemiological associations found between KRAS mutations and dietary factors.
Topics: Acrylamide; Beverages; Colorectal Neoplasms; Dairy Products; Diet; Dietary Fats; Dietary Fiber; Dietary Proteins; Food; Fruit; Genes, ras; Humans; Mutation; Nutrients; Vegetables
PubMed: 32723394
DOI: 10.1186/s12885-020-07189-2 -
Annals of Palliative Medicine Sep 2020Osimertinib, a third-generation tyrosine kinase inhibitor (TKI), is the only Food and Drug Administration-approved third-generation epidermal growth factor receptor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osimertinib, a third-generation tyrosine kinase inhibitor (TKI), is the only Food and Drug Administration-approved third-generation epidermal growth factor receptor (EGFR)TKI. Osimertinib is a cancer medicine that interferes with the growth and spread of cancer cells in the body. Osimertinib is used to treat a certain type of non-small cell lung cancer. We review some of the main challenges in targeting EGFR, including lack of central nervous system penetration with most tyrosine kinase inhibitors, activity of osimertinib penetrating blood-brain barrier and the efficacy of osimertinib.
METHODS
Guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, we conducted a systematic literature search in the databases PubMed, EMBASE, ISI Web of Science database on January 30, 2020, searching for studies investigating the osimertinib efficacy on patients with CNS metastases in EGFR-mutant non-small cell lung cancer (NSCLC). And Newcastle-Ottawa Scale (NOS) was used to assess the certainty in the evidence.
RESULTS
The pooled results showed that the overall response rate (ORR) and disease control rate (DCR) were 70% and 92%, respectively, in patients with T790M mutations. The efficacy of osimertinib was confirmed by the median progression free survival (PFS). In untreated advanced EGFR-mutated NSCLC with CNS metastases patients, the pooled ORR and DCR of osimertinib were 71% and 93%, respectively. And the combined median PFS, achieved by osimertinib, was 12.21 months. Above data proved that osimertinib has well activity in disease control, especially in first line.
CONCLUSIONS
This meta-analysis confirmed that in treatment-naive advanced NSCLC CNS metastases harboring EGFR-TKI-sensitizing mutations, Osimertinib showed impressive antitumor activity.
Topics: Acrylamides; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; Central Nervous System; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors
PubMed: 32954743
DOI: 10.21037/apm-20-605 -
International Journal of Cancer Jul 2019Osimertinib is the only Food and Drug Administration-approved third-generation epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI). A meta-analysis... (Meta-Analysis)
Meta-Analysis
Osimertinib is the only Food and Drug Administration-approved third-generation epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI). A meta-analysis was performed to aggregate the mixed results of published clinical trials to assess the efficacy and safety of osimertinib. A systematic search of the PubMed, Web of Science, and Cochrane Library electronic databases was performed to identify eligible literature. The primary endpoints were overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and adverse events (AEs). A total of 3,086 advanced nonsmall cell lung cancer (NSCLC) patients from 11 studies have been identified. The aggregate efficacy parameters for treatment-naïve patients with EGFR-TKI-sensitizing mutations are as follows: ORR 79% (95% CI 75-84%), DCR 97% (95% CI 95-99%), 6-month PFS 83% (95% CI 80-87%), and 12-month PFS 64% (95% CI 59-69%). The aggregate efficacy parameters for advanced NSCLC harboring T790M mutations after earlier-generation EGFR-TKI therapy are as follows: ORR 58% (95% CI 46-71%), DCR 80% (95% CI 63-98%), 6-month PFS 63% (95% CI 58-69%), and 12-month PFS 32% (95% CI 17-47%). EGFR-TKI-naïve patients with EGFR-positive mutations tend to have longer median PFS than EGFR-TKI-pretreated counterparts (19.17 vs. 10.58 months). The most common AEs were diarrhea and rash, of which the pooled incidences were 44 and 42%, respectively. Generally, osimertinib is a favorable treatment option for previously treated T790M mutation-positive advanced NSCLC as well as a preferable therapy for untreated EGFR mutation-positive advanced NSCLC. Additionally, osimertinib is well tolerated by most patients.
Topics: Acrylamides; Aniline Compounds; Animals; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic
PubMed: 30613959
DOI: 10.1002/ijc.32097 -
Expert Review of Pharmacoeconomics &... Jun 2022The most common type of lung cancer is advanced and mutant non-small cell lung cancer (NSCLC). Although targeted tyrosine kinase inhibitors (TKIs) have reconstructed the...
BACKGROUND
The most common type of lung cancer is advanced and mutant non-small cell lung cancer (NSCLC). Although targeted tyrosine kinase inhibitors (TKIs) have reconstructed the care of these patients, the resistance of TKIs to the secondary EGFR-T790M mutation in advanced or metastatic NSCLC led to the introduction of the third generation of them, like osimertinib. Osimertinib has represented a remarkable increase in progression-free survival (PFS) and a decrease in death and hazard ratios in patients with required T790 mutation and sensitizing EGFR mutation without T790M. We aimed to evaluate the cost-effectiveness of osimertinib for the treatment of these patients compared to chemotherapy or immunotherapy with the last generations of EGFR-TKIs.
AREAS COVERED
Electronic searches were conducted on PubMed, Embase, Science Direct, Scopus, , Web of Knowledge, NHSEED, NHS Health Technology assessment (CRD), and Cost-Effectiveness Analysis Registry databases. Related articles were reviewed from January 2015 to the end of August 2020. Out of 2708 initial studies, 10 articles had the inclusion criteria.
EXPERT OPINION
Although osimertinib improves the quality of life and PFS for the mentioned patients based on its greater efficacy compared to standard EGFR-TKIs and chemotherapy, its high cost prevents considering it a cost-effective option. And, since most entered studies have been done in developed countries, it certainly does not true to extend these results to low-income and developing countries. Therefore, further studies in those countries are needed to evaluate the cost-effectiveness of osimertinib for sensitizing EGFR mutation without T790M and required T790M in advanced or metastatic NSCLC.
Topics: Acrylamides; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; Cost-Benefit Analysis; ErbB Receptors; Humans; Indoles; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Pyrimidines; Quality of Life
PubMed: 34846235
DOI: 10.1080/14737167.2022.2011721 -
Critical Reviews in Food Science and... 2024Acrylamide (AA) is a toxic substance formed in many carbohydrate-rich food products, whose formation can be reduced by adding some additives. Furthermore, the type of...
Acrylamide (AA) is a toxic substance formed in many carbohydrate-rich food products, whose formation can be reduced by adding some additives. Furthermore, the type of food consumed determines the AA intake. According to the compiled information, the first route causing AA formation is the Maillard reaction. Some interventions, such as reducing AA precursors in raw materials, (i.e., asparagine), reducing sugars, or decreasing temperature and processing time can be applied to limit AA formation in food products. The L-asparaginase is more widely used in potato products. Also, coatings loaded with proteins, enzymes, and phenolic compounds are new techniques for reducing AA content. Enzymes have a reducing effect on AA formation by acting on asparagine; proteins by competing with amino acids to participate in Maillard, and phenolic compounds through their radical scavenging activity. On the other hand, some synthetic and natural additives increase the formation of AA. Due to the high exposure to AA and its toxic effects, it is essential to recognize suitable food additives to reduce the health risks for consumers. In this sense, this study focuses on different additives that are proven to be effective in the reduction or formation of AA in food products.
Topics: Asparagine; Acrylamide; Hot Temperature; Carbohydrates; Asparaginase; Maillard Reaction
PubMed: 36194060
DOI: 10.1080/10408398.2022.2126428 -
Phytotherapy Research : PTR Jan 2020Quercetin is one of the most abundant flavonoids in human diet that has been reported to exhibit a wide range of pharmacological properties. The biochemical and...
Quercetin is one of the most abundant flavonoids in human diet that has been reported to exhibit a wide range of pharmacological properties. The biochemical and molecular mechanisms involved in the hepatoprotective activity of quercetin were discussed in this review. Quercetin exhibited hepatoprotective activity against 2-butoxyethanol, acrylamide, acrylonitrile, aflatoxin B1, aroclor-1254, arsenic, sodium arsenite, azathioprine, cadmium chloride, carbon tetrachloride, chlorpyrifos, cyclosporine A, diazinon, dimethylnitrosamine, doxorubicin, epirubicin, ethanol, fenvalerate, isoniazide, rifampicin, lead acetate, lindane, D-galactosamine, methotrexate, methylmercury, nickel sulfate, paracetamol, perfluorooctanoic acid, polychlorinated biphenyls, pyrrolizidine alkaloid clivorine, rotenone, sodium fluoride, streptazotocin, tert-butyl hydroperoxide, thioacetamide, titanium dioxide, tumor necrosis factor-α, tripterygium glycoside, triptolide, ultraviolet A light, concavalin A, bisphenol, and ischemia-induced hepatotoxicity in various animal models due to its antioxidant, free radical-scavenging,anti-inflammatory, antiapoptotic, and cytochrome P450 2E1 (CYP2E1) inhibitory activities. In this review, we provide an overview of the possible mechanisms by which quercetin reduced the hepatotoxicity of different hepatotoxicants. This will help the toxicologists, pharmacologists, and chemists to develop new safer pharmaceutical products with quercetin and other hepatotoxicants.
Topics: Animals; Antioxidants; Humans; Liver; Male; Quercetin; Rats; Rats, Sprague-Dawley; Rats, Wistar
PubMed: 31617262
DOI: 10.1002/ptr.6503 -
BMC Cancer Jan 2019Osimertinib, the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has become the standard treatment in cases where rebiopsy...
Impact on prognosis of rebiopsy in advanced non-small cell lung cancer patients after epidermal growth factor receptor-tyrosine kinase inhibitor treatment: a systematic review.
BACKGROUND
Osimertinib, the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has become the standard treatment in cases where rebiopsy reveals T790M mutation after the first-line EGFR-TKI treatment. However, the prognosis of patients after rebiopsy, the most important outcome for cancer patients, has not been described sufficiently. This systematic review aimed to clarify whether rebiopsy contributes to improved prognosis in the first- or second-generation EGFR-TKI refractory patients.
METHODS
Using free word and control terms related to "non-small cell lung cancer" and "rebiopsy," we searched studies from Medical Literature Analysis and Retrieval System Online via PubMed, Embase, Cochrane Central Register of Controlled Trials, and World Health Organization International Clinical Trials Registry Platform. We included cohort studies and case reports written in English and judged whether each study answers our research questions.
RESULTS
Of the 144 studies included, only one reported the prognosis of patients with/without rebiopsy showing that in EGFR-TKI refractory non-small cell lung cancer patients, the post-progression survival (PPS) was significantly longer in patients who received rebiopsy and treatment based on a resistant mechanism (median PPS 24.2 months) than those who received rebiopsy and salvage regimen (median PPS 15.2 months, p = 0.002) and who did not receive rebiopsy (median PPS 9.7 months, p < 0.001). Most of the other studies reported the detection rate of T790M mutation or rebiopsy procedure.
CONCLUSIONS
Only a few previous studies have investigated the effectiveness of rebiopsy. Hence, further study is needed to determine the prognosis or adverse events of rebiopsy.
Topics: Acrylamides; Aniline Compounds; Antineoplastic Agents; Biopsy; Carcinoma, Non-Small-Cell Lung; Disease Progression; Drug Resistance, Neoplasm; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Piperazines; Prognosis; Protein Kinase Inhibitors; Survival Analysis
PubMed: 30683066
DOI: 10.1186/s12885-019-5309-x