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International Journal of Environmental... Jul 2022Despite substantially elevated risk of serious adverse events (SAEs) from targeted therapy in combination with chemotherapy, comprehensive pharmacovigilance research is... (Meta-Analysis)
Meta-Analysis
Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis.
Despite substantially elevated risk of serious adverse events (SAEs) from targeted therapy in combination with chemotherapy, comprehensive pharmacovigilance research is limited. This study aims to systematically assess SAE risks of commonly prescribed targeted agents (bevacizumab, cetuximab, and panitumumab) in patients with rat sarcoma viral oncogene homolog (RAS) wild-type metastatic colon cancer. Keyword searches of Cochrane Library, Clinical Key and MEDLINE were conducted per PRISMA-NMA guidelines. Frequentist network meta-analysis was performed with eight randomized controlled trials to compare relative risk (RR) of 21 SAE profiles. The risks of hematological, gastrointestinal, neurological SAE were insignificant among targeted agents (p > 0.05). The risk of serious hypertension was substantially elevated in bevacizumab-based chemotherapy (p < 0.05), whereas panitumumab-based chemotherapy had markedly elevated risk of serious thromboembolism (RR 3.65; 95% CI 1.30−10.26). Although both cetuximab and panitumumab demonstrated increased risk of serious dermatological and renal toxicities, panitumumab-based chemotherapy has relatively higher risk of skin toxicity (RR 15.22; 95% CI 7.17−32.35), mucositis (RR 3.18; 95% CI 1.52−6.65), hypomagnesemia (RR 20.10; 95% CI 5.92−68.21), and dehydration (RR 2.81; 95% CI 1.03−7.67) than cetuximab-based chemotherapy. Thus, further studies on risk stratification and SAE management are warranted for safe administration of targeted agents.
Topics: Antineoplastic Agents; Bevacizumab; Cetuximab; Colorectal Neoplasms; Humans; Network Meta-Analysis; Panitumumab
PubMed: 35954563
DOI: 10.3390/ijerph19159196 -
Immunopharmacology and Immunotoxicology Feb 2023Cetuximab and panitumumab are common antibodies against epidermal growth factor receptor (EGFR) that can be used in combination with chemotherapy for the treatment of... (Meta-Analysis)
Meta-Analysis
AIM
Cetuximab and panitumumab are common antibodies against epidermal growth factor receptor (EGFR) that can be used in combination with chemotherapy for the treatment of metastatic colorectal cancer (mCRC). Although these two drugs are considered to be very similar, differences in the efficacy and safety of cetuximab and panitumumab are still unclear. We conducted this meta-analysis to explore the effects and adverse reactions of cetuximab and panitumumab in the treatment of mCRC.
METHODS
We searched PubMed, the Cochrane Library, Embase, Web of Science, China national knowledge infrastructure (CNKI) and WanFang databases to identify records related to the efficacy and safety of cetuximab and panitumumab in the treatment of mCRC. The search terms were "cetuximab," "panitumumab," and "colorectal cancer." The deadline of searching was April 2022. Review manager 5.4 software was used to perform the statistical analysis for this meta-analysis. Pooled hazard ratio (HR) with 95% confidence intervals (CI) were calculated to evaluate the overall survival (OS) and progression free survival (PFS) of cetuximab and panitumumab in the treatment of mCRC.
RESULTS
There was no significant difference in OS, PFS, and response rate (RR) between cetuximab arm and panitumumab arm (OS: HR = 0.91, 95% CI = 0.81-1.03, = .14; PFS: HR = 0.92, 95% CI = 0.83-1.02, = .11; RR: OR = 1.22, 95% CI = 0.96-1.61, = .14). We also did not observe any statistical difference between both arms in incidence of acneiform rash, severe acneiform rash, diarrhea, and severe diarrhea (acneiform rash: OR = 1.09, 95% CI = 0.84-1.42, = .51; severe acneiform rash: OR = 1.50, 95% CI = 0.80-2.81, = .21; diarrhea: OR = 1.08, 95% CI = 0.82-1.42, = .58; severe diarrhea: OR = 0.90, 95% CI = 0.44-1.84, = .77). The incidence of paronychia was decreased in the panitumumab arm, but that of hypomagnesemia and severe hypomagnesemia were decreased in the cetuximab arm. (paronychia: OR = 0.74, 95% CI = 0.55-1.00, = .05; hypomagnesemia: OR = 1.85, 95% CI =1.41-2.41, .00001; severe hypomagnesemia: OR = 2.66, 95% CI = 1.52-4.67, .0006).
CONCLUSION
There was no significant difference in OS, PFS and RR between the cetuximab arm and panitumumab arm in the treatment of mCRC. For adverse reactions, the incidence of paronychia was decreased in the panitumumab arm, and the incidence of hypomagnesemia was deceased in the cetuximab arm.
Topics: Humans; Panitumumab; Cetuximab; Antibodies, Monoclonal; Proto-Oncogene Proteins p21(ras); Colorectal Neoplasms; Paronychia; Colonic Neoplasms; Rectal Neoplasms; Exanthema; Antineoplastic Combined Chemotherapy Protocols
PubMed: 35950851
DOI: 10.1080/08923973.2022.2112222 -
Frontiers in Oncology 2021Systemic treatments, namely, either monotherapy or combination therapy, are commonly administered to patients with advanced or metastatic colorectal cancer (CRC). This...
BACKGROUND
Systemic treatments, namely, either monotherapy or combination therapy, are commonly administered to patients with advanced or metastatic colorectal cancer (CRC). This study aimed to provide the complete efficacy and safety profiles and ranking of systemic therapies for the treatment of unresectable advanced or metastatic CRC.
METHODS
We searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception until June 30, 2021, and also the bibliographies of relevant studies. Randomized controlled trials comparing two or more treatments, namely, at least capecitabine, 5-fluorouracil, leucovorin, irinotecan, bevacizumab, cetuximab, oxaliplatin, or panitumumab were investigated. A network meta-analysis using the Bayesian approach was performed to compare the efficacy and safety of treatments. The surface under the cumulative ranking curve (SUCRA) was calculated for the probability of each treatment as the most effective. The overall response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), adverse events (AEs) grade ≥3, and serious adverse events (SAEs) were evaluated.
RESULTS
One hundred two publications with 36,147 participants were assigned to 39 different treatments. Among 11 treatments with full information on six outcomes, FOLFIRI/FOLFOX/FOLFOXIRI + bevacizumab significantly improved both the ORR and DCR, compared to FOLFIRI. Although FOLFOX and FOLFIRI/FOLFOX + cetuximab significantly prolonged both OS and PFS, treatments were comparable in terms of AEs grade ≥3 and SAEs. The top highest SUCRA values were observed in the FOLFOXIRI + panitumumab group for ORR (96%) and DCR (99%), FOLFIRI + bevacizumab + panitumumab group for OS (62%) and PFS (54%), and FOLFOXIRI + bevacizumab group for AEs grade ≥3 (59%) and SAEs (59%) outcomes.
CONCLUSIONS
These findings suggest an available range of systemic treatment therapies with different efficacy and safety profiles with patients. Further investigations of the side effects and mutation status are required to confirm our findings.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42019127772.
PubMed: 35223449
DOI: 10.3389/fonc.2021.756214 -
Clinical Colorectal Cancer Sep 2022Few data from randomized clinical trials (RCTs) investigating the efficacy of post-induction strategies after the first-line treatment with anti-Epidermal Growth Factor... (Meta-Analysis)
Meta-Analysis Review
Few data from randomized clinical trials (RCTs) investigating the efficacy of post-induction strategies after the first-line treatment with anti-Epidermal Growth Factor Receptor (EGFR) in patients with metastatic colorectal cancer (mCRC) are available. A systematic review and metanalysis might therefore be useful to highlight and even strengthen these data. A literature search in Pubmed, Embase, American Society of Clinical Oncology (ASCO) Annual Meetings, ASCO Gastrointestinal Symposia, and European Society for Medical Oncology (ESMO) Congresses was performed. The search included RCTs of patients with mCRC treated with an initial period of cytotoxic chemotherapy (CT) in association with anti-EGFR (ie, panitumumab or cetuximab) as first-line regimen, and then switched to one of the following strategies: observation; maintenance with anti-EGFR, fluoropyrimidine (FP), or both; or continuing the induction regimen until disease progression or unacceptable toxicity. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the Mantel-Haenszel method fixed-effect model or the DerSimonian-Laird method random-effect model according to heterogeneity (I). Analysis was performed on June 9, 2021. 7 studies (all phase II trials), including 1038 patients, were considered eligible for the meta-analysis. In all studies, CT (induction or maintenance with FP) + anti-EGFR until disease progression or unacceptable toxicity prolonged OS (HR = 0.72 [95%CI 0.61-0.86]; P < .01) and PFS (HR = 0.76, 95%CI 0.68-0.85; P < .01) compared to other agents (FP ± bevacizumab) or observation. Subgroup analyses for OS and PFS were performed according to type of maintenance therapy (containing or not containing single-agent anti-EGFR). Within patients evaluable for OS, CT + anti-EGFR combinations continued until disease progression were able to decrease the risk of death by 32% (HR 0.68; 95% CI 0.56-0.84; P < .01) and the risk of progression by 25% (HR 0.75; 95% CI 0.65-0.85; P < .01) over no maintenance or maintenance with anti-EGFR alone. Conversely, combination of CT + anti-EGFR were no better over anti-EGFR with FP in term of OS (HR = 0.81 [95%CI 0.60-1.09]; P = .17) and PFS (HR = 0.81 [95% 0.64, 1.01]; P = .06). Maintenance treatment with anti-EGFR + FP might be regarded as the better option following anti-EGFR based induction treatment in RAS wild-type mCRC, in terms of efficacy. This effect might be particularly amplified in left-sided BRAF wild-type mCRC patients. A higher level of evidence coming from phase III trials is auspicable.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Disease Progression; Humans; Panitumumab
PubMed: 35184993
DOI: 10.1016/j.clcc.2021.12.005 -
Journal of the European Academy of... Apr 2022Long eyelashes have been popularized and many commercially available products exist to achieve eyelash growth as a desired cosmetic effect. Eyelash trichomegaly may be... (Review)
Review
Long eyelashes have been popularized and many commercially available products exist to achieve eyelash growth as a desired cosmetic effect. Eyelash trichomegaly may be induced by medications, procedures, or be related to medical conditions; however, the exact mechanisms that govern eyelash growth are not well elucidated. This study aims to identify and summarize aetiologies associated with eyelash trichomegaly. We report a systematic review of 148 clinical trials, prospective and retrospective studies, and case reports describing all evidence-based potential aetiologies of eyelash trichomegaly obtained from the Medline/PubMed and Cochrane Library through January 2021. Inclusion criteria were defined as (i) human studies involving congenital and acquired diseases in which eyelash trichomegaly is a characteristic or (ii) assessment of trichomegaly as an adverse or desired effect of a medication or procedure. Exclusion criteria included: animal studies, articles not available in English, outcomes unrelated to eyelash trichomegaly, and secondary review articles. Pharmacologic agents associated with eyelash trichomegaly included prostaglandin analogues (15-keto fluprostenol isopropyl ester, bimatoprost, latanoprost, and travoprost), epidermal growth factor receptor inhibitors (cetuximab, erlotinib, and panitumumab), interferon-alpha, and calcineurin inhibitors (tacrolimus and cyclosporine). Surgical procedures of the eyelid, as well as allergic rhinitis, atopic dermatitis, HIV, ichthyosis vulgaris (IV), uveitis, and vernal keratoconjunctivitis were also associated with increased eyelash growth. Congenital disorders associated with lengthened eyelashes included Cantú syndrome, CHOPS syndrome, Coffin-Siris syndrome, congenital heart disease, Cornelia de Lange syndrome, Costello syndrome, familial trichomegaly, Floating Harbor syndrome, Hermansky-Pudlak syndrome, Kabuki-Makeup syndrome, KBG syndrome, Oliver-McFarlane syndrome, Rubinstein-Taybi syndrome, and Smith-Magenis syndrome. While the most common cause of eyelash trichomegaly is topical bimatoprost use, better understanding of pathways implicated in eyelash trichomegaly may lead to the discovery of additional medications to stimulate eyelash growth and create avenues for future therapeutic interventions.
Topics: Abnormalities, Multiple; Animals; Bone Diseases, Developmental; Facies; Humans; Intellectual Disability; Prospective Studies; Retrospective Studies; Tooth Abnormalities
PubMed: 34919300
DOI: 10.1111/jdv.17877 -
Molecular Diagnosis & Therapy Nov 2021Colorectal cancer (CRC) is one of the major causes of mortality and morbidity worldwide. The median overall survival (OS) of patients with metastatic CRC (mCRC) has...
INTRODUCTION
Colorectal cancer (CRC) is one of the major causes of mortality and morbidity worldwide. The median overall survival (OS) of patients with metastatic CRC (mCRC) has doubled over the last 20 years partly due to the introduction of advanced biologic therapies. However, these treatment modalities bear significant costs on healthcare systems globally, and may jeopardize their fiscal sustainability. The aim of this systematic review was to critically appraise the economic evaluations of monoclonal antibodies in mCRC.
METHODOLOGY
A literature search was performed in the electronic databases of: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, EMBASE, EMBASE Alert, PUBMED, NHS Economic Evaluation and Health Technology Assessment Database for full articles published from 1 January 2013 to 31 December 2020.
RESULTS
Twenty economic analyses were identified in the literature that fulfilled the inclusion criteria and evaluated the cost-effectiveness of (a) bevacizumab as first-line treatment for mCRC and as maintenance treatment, (b) cetuximab as first-line treatment, (c) panitumumab versus bevacizumab and cetuximab versus bevacizumab as first-line treatment, (d) aflibercept and ramucirumab as second-line treatment, (e) cetuximab and panitumumab as third-line treatment, (f) cetuximab versus panitumumab as later lines of treatment, and (g) RAS testing prior to anti-epidermal growth factor receptor (EGFR) treatment.
CONCLUSIONS
Bevacizumab in combination with chemotherapy is cost-effective as neither first-line treatment nor maintenance treatment. Sequential treatment with bevacizumab in first-line and second-line treatment was also not cost-effective. Testing for KRAS and extended RAS mutations is cost-effective and should be performed prior to anti-EGFR treatment. In the RAS wild-type subgroup of mCRCs the use of anti-EGFR (panitumumab or cetuximab) in first-line treatment leads to a more favorable cost-effectiveness profile than the corresponding anti-VEGF (bevacizumab). Cetuximab is not cost-effective as a first-line treatment. Anti-EGFR administration is not a cost-effective strategy in third-line treatment, even for RAS wild-type mCRCs, compared to best supportive care. Aflibercept was superior to ramucirumab and costed less, but neither were cost-effective compared to standard care.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Bevacizumab; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Cost-Benefit Analysis; Humans; Panitumumab
PubMed: 34816395
DOI: 10.1007/s40291-021-00560-4 -
Advances in Therapy Oct 2020Although various therapies are available for the treatment of metastatic colorectal cancer (mCRC), there is lack of head-to-head evidence. Recent studies have... (Meta-Analysis)
Meta-Analysis
Efficacy and Safety of Regorafenib in Combination with Chemotherapy as Second-Line Treatment in Patients with Metastatic Colorectal Cancer: A Network Meta-Analysis and Systematic Literature Review.
INTRODUCTION
Although various therapies are available for the treatment of metastatic colorectal cancer (mCRC), there is lack of head-to-head evidence. Recent studies have demonstrated the efficacy of chemotherapy in combination with different biological agents including regorafenib in second-line therapy in patients with mCRC. We conducted a network meta-analysis (NMA) to estimate the relative efficacy and safety of regorafenib in combination with chemotherapy compared to other biological agents with chemotherapy combinations.
METHODS
A literature search was conducted in PubMed, Embase, and Cochrane databases to identify all randomized controlled trials (RCTs) evaluating the efficacy and safety of bevacizumab, regorafenib, panitumumab, cetuximab, ramucirumab, conatumumab, ganitumab, and aflibercept in combination with chemotherapy against chemotherapy alone as second-line setting from inception to 7 February 2019 in patients with mCRC. The survival outcomes were analyzed by the frequentist statistical approach (R software, netmeta package) while the level of individual treatment arms was assessed using the Bayesian method (R software, gemtc package).
RESULTS
We identified 12 articles involving eight RCTs studies analyzing 6805 patients. The studies compared bevacizumab (3), regorafenib (1), panitumumab (2), cetuximab (3), ramucirumab (1), conatumumab (1), ganitumab (1), and aflibercept (1) against chemotherapy alone as comparator. The progression-free survival (PFS) revealed that regorafenib performed better than aflibercept (HR 0.9631, 95% CI 0.6785-1.367), ganitumab (HR 0.7228, 95% CI 0.3985-1.3109), panitumumab (HR 0.9653, 95% CI 0.6781-1.3742), and ramucirumab (HR 0.9206, 95% CI 0.6504-1.303). Regorafenib performed better than bevacizumab (OR 0.797, 95% CI 0.328-1.88) in terms of tumor response. Safety analysis showed that regorafenib performed better in reducing grade ≥ 3 adverse events (AE) than cetuximab and conatumumab, neutropenia than conatumumab, and fatigue than cetuximab.
CONCLUSIONS
Regorafenib combined with chemotherapy might be a potential alternative to conventional therapeutic options in second-line treatment of patients with metastatic colorectal cancer and could be considered as the best option for treating patients with KRAS and BRAF mutated mCRC. However future RCTs are needed to confirm these results.
Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Disease-Free Survival; Humans; Network Meta-Analysis; Phenylurea Compounds; Pyridines
PubMed: 32770529
DOI: 10.1007/s12325-020-01447-2 -
Medicine Jul 2020Test on the KRAS somatic mutation status is necessary before cetuximab and panitumumab treatments are given to colorectal cancer patients. Metastatic colorectal cancer... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Test on the KRAS somatic mutation status is necessary before cetuximab and panitumumab treatments are given to colorectal cancer patients. Metastatic colorectal cancer patients sometimes lack tumor tissue samples, and the testing of KRAS mutation in plasma samples requires highly sensitive methods.
OBJECTIVES
The aim of this study was to evaluate the accuracy of digital PCR in detecting KRAS mutation in plasma samples of colorectal cancer patients.
DATA SOURCES
Literature research was conducted in Pubmed, Embase, and Cochrane Library.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
Database searching found 188 relevant studies. After removing duplicates, eligible studies were selected from 151 publications using the following exclusion criteria: STUDY APPRAISAL AND SYNTHESIS METHODS:: Data were extracted from the eligible studies by 2 independent researchers. Pooled accuracy parameters were calculated from those extracted data using Meta-DiSc and STATA software.
RESULTS
Twelve eligible studies were selected for the systematic review and meta-analysis. After calculation, the pooled sensitivity and specificity were 0.83 (95% CI: 0.79-0.86) and 0.91 (95%CI: 0.88-0.93), respectively. Pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 7.30 (95%CI: 4.78-11.17), 0.22 (95%CI: 0.15-0.32), and 41.00 (95%CI: 21.07-79.78), respectively. Area under curve of the summarized ROC curve was 0.9322.
LIMITATIONS
Although no significant bias was identified, number of included studies was still quite small, especially in subgroup analysis.
CONCLUSIONS AND IMPLICATION OF KEY FINDINGS
Digital PCR showed high accuracy and could be a reliable detection method for KRAS mutation in plasma samples. Large-cohort prospective study is required to further confirm the usefulness of digital PCR in KRAS mutation detection.
Topics: Adult; Aged; Colorectal Neoplasms; Female; Humans; Male; Middle Aged; Mutation; Polymerase Chain Reaction; Proto-Oncogene Proteins p21(ras); ROC Curve; Reproducibility of Results; Sensitivity and Specificity
PubMed: 32664155
DOI: 10.1097/MD.0000000000021171 -
Critical Reviews in Oncology/hematology Sep 2020The most effective regimen is unclear for patients with recurrent or metastatic head and neck squamous cell carcinomas (R/M HNSCC). We performed a systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The most effective regimen is unclear for patients with recurrent or metastatic head and neck squamous cell carcinomas (R/M HNSCC). We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating only systemic therapy for R/M HNSCC.
METHODS
This systematic review followed PRISMA and the Cochrane Collaboration Handbook for Systematic Reviews of Interventions. Endpoints included overall survival (OS), progression-free survival (PFS) and overall response rates (ORR).
RESULTS
55 RCTs from 1990-November 2019 qualified for review (n=12132). Only PD-1/PDL-1 inhibitors increased OS in R/M HNSCC platinum-resistant disease against their control (HR = 0·79, 95%CI 0·70-0.90, p<0·001), especially for PD-L1 ≥ 1% expressing tumours (HR = 0·72, 95%CI 0·60-0·86, p<0·001). PFS was prolonged for anti-EGFR agents against methotrexate when used in a second line setting (HR = 0·74, 95 %CI 0·62-0·87, p=0·001), and when cetuximab (HR = 0·60, 95%CI 0·49-0·72, p<0·0001) and panitumumab (HR = 0·76, 95%CI 0·65-0·89, p=0·001) were introduced to platinum-based regimens for first-line treatment.
CONCLUSIONS
PD-1/PD-L1 inhibitors may represent the future of R/M HNSCC treatment. However, EGFR inhibitors may still play improve clinical outcomes.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Head and Neck Neoplasms; Humans; Methotrexate; Neoplasm Recurrence, Local; Squamous Cell Carcinoma of Head and Neck
PubMed: 32569853
DOI: 10.1016/j.critrevonc.2020.102984 -
Frontiers in Pharmacology 2020Patients with locally advanced rectal cancer (LARC) are at higher risk of local and distant recurrence and are thus more vulnerable to metastatic diseases. Neoadjuvant...
BACKGROUND
Patients with locally advanced rectal cancer (LARC) are at higher risk of local and distant recurrence and are thus more vulnerable to metastatic diseases. Neoadjuvant chemoradiotherapy (nCRT) and subsequent curative resection with total mesorectal excision (TME) followed by adjuvant chemotherapy have been recommended by the National Comprehensive Cancer Network (NCCN) guidelines as standard of care for LARC patients. However, the efficacy of the addition of epidermal growth factor receptor (EGFR) inhibitors in kirsten rat sarcoma viral oncogene (KRAS)-wild type LARC patients remains uncertain.
MATERIALS
PubMed, Embase, and Web of Science were searched to retrieve records on the application of EGFR inhibitors in a neoadjuvant setting for LARC patients. pCR was used as surrogate endpoint to perform data synthesis in a single-arm setting.
RESULTS
Ten cohorts covering 540 subjects were eligible in this systematic review. The pooled pCR rate for EGFR inhibitors was 15% (95% confidence interval (95% CI), 11-20%; I = 55.2%); the pooled estimates of Grade 3/4 diarrhea, Grade 3/4 hand-foot syndrome, Grade 3/4 acneiform rash were 17% (95% CI, 4-34%; I = 93.3%), 2% (95% CI, 0-5%; I = 13.7%), and 15% (95% CI, 9-22%; I = 65.4%), respectively.
CONCLUSION
The addition of EGFR inhibitors in the nCRT for KRAS-wild type LARC patients provides comparable efficacy and acceptable safety. However, the results should be interpreted cautiously due to the small amount of relevant data and need further confirmation by more future studies.
PubMed: 32499700
DOI: 10.3389/fphar.2020.00706