Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer

Sano, Kazumi; Nakadate, Kazuhiko; Hanada, Kazuhiko

doi:10.21203/rs.2.20607/v2

Cited by 4 publications

(5 citation statements)

References 9 publications

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“…Meanwhile, patients with orally administered drugs stopped taking medication and reduced drug dosage, due to being unable to tolerate the ADRs. Therefore, the compliance of patients with orally targeted drugs decreased, while the incidence of missed dosages and not taking drugs on time increased, this was con rmed by Sano et al (12). In this study, 62.2% of patients stopped taking drugs and 62.8% did not take drugs on time due to adverse drug reactions.…”

Section: Discussionsupporting

confidence: 78%

“…In addition, gastrointestinal reactions, hypertension, coagulation disorders and cardiotoxicity were also common ADRs, which led to poor compliance, resulting in the negative impact on the QoL and daily activity of cancer patients (11). Some researches indicated that about 32% of the patients receiving targeted molecular treatment experience unplanned discontinuation due to adverse reactions, which lead to poor therapeutic effect, prognosis and even lead to cancer recurrence or progression (12).…”

Section: Introductionmentioning

confidence: 99%

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Adverse Reactions of Targeted Therapy in Cancer Patients: A Retrospective Study of Hospital Medical Data in China

Du¹,

Larcher

Tang³

et al. 2020

Preprint

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Background: The adverse reactions (ADR) of targeted therapy were closely related to the treatment efficacy, quality of life (QoL) and prognosis of cancer patients. However, few studies analyzed the ADR of targeted therapy and their effects on cancer patients. This study was conducted to describe the incidence and characteristics of ADR in cancer patients with targeted therapy and outcomes associated with ADR based on hospital medical data.Methods: A retrospective secondary data analysis was conducted using ADR data in hospital medical record collected from a cohort (n=2,703 with targeted therapy) in three hospitals of Henan, China from January 2018 to December 2019. The type, classification, occurrence time and duration of ADR, medication compliance and drug application, QoL, disease progress and survival of patients were analyzed.Results: A total of 485 patients met the inclusion criteria. 296 (61.0%) patients had ADR during target therapy. The top five ADR in this study were damage to skin, fatigue, mucosal damage, hypertension and gastrointestinal discomfort. 62.1% of the ADR were mild to moderate, more than half of the ADR occurred within one month, 68.6% ADR lasted more than one month. Older patients (P=0.022) and patients with lower education level (P=0.036), more than 2 comorbidities (P=0.021), longer medication time (P=0.022), drug combination (P=0.033) and intravenous administration (P=0.019) were more likely to have ADR. Those who had ADR were more likely to stop taking (P=0.025), change (P=0.010), adjust (P=0.019), or not take the medicine on time (P=0.022), or undergo cancer recurrence (P=0.027) and show higher rates of metastasis (P=0.009) .Conclusion: The incidence of ADR in cancer patients during targeted therapy was high. Age, education level, comorbidity and medication strategy can affect ADR. Furthermore, ADR would affect the treatment and prognosis of patients. We should pay more attention to these ADRs and develop effective management strategies.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Adverse Reactions of Targeted Therapy in Cancer Patients: A Retrospective Study of Hospital Medical Data in China

Du¹,

Larcher

Tang³

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Although these drugs or drug combinations are believed to prolong the lives of patients and improve their quality of life, there are still many shortcomings: (1) the sensitivity of patients to these antitumor drugs is purely individual [13][14][15]; (2) antitumor drug treatment is prone to drug resistance [13][14][15]; and (3) the side effects of antitumor drug treatment are very serious [16]. Small molecule inhibitors or therapeutic antibodies targeting the PD-1/PD-L1 pathway have been available for a short time, and the influencing factors or biomarkers that influence the efficacy of these drugs are not yet clear [17][18][19].…”

Section: Ivyspring International Publishermentioning

confidence: 99%

miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway

Meng

Wang

et al. 2022

J. Cancer

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Background:The Notch pathway, which is related to the drug-resistance of lung adenocarcinoma (LUAD) type of non-small cell lung cancer (NSCLC) cells, is activated by cleavage of Notch proteins mediated by ADAMs, ADAM10 or ADAM17. Methods: In the present study, our results demonstrated that of these two ADAMs, the expression of ADAM10 in clinical samples of the LUAD type of NSCLC was much higher than that of ADAM17, while miR-140-3p -an miRNA that could target ADAM10 -was identified by an online tool: miRDB (miRNA database). The detail function and mechanism of miR-140-3p in regulating the sensitivity of NSCLC cells to antitumor drugs was systematically explored in vitro and in vivo. Results: In A549, a typical NSCLC LUAD cell line, miR-140-3p decreased ADAM10 expression and repressed activation of the Notch pathway by repressing cleavage of Notch proteins. The expression of miR-140-3p was negatively related to ADAM10 in clinical specimens. Nucleocytoplasmic separation/ subfraction assays showed that miR-140-3p was able to inhibit the cleavage of Notch protein, and led to the accumulation of Notch intracellular domains (NICD) in the nucleus. Overexpression of miR-140-3p enhanced the sensitivity of A549 cells to antitumor agents by targeting the 3'UTR region of ADAM10 mRNA in both cultured cells and in vivo models. Conclusion: ADAM10 plays a major role in LUAD, and miR-140-3p acts on ADAM10 and inhibits its expression and the cleavage of Notch protein, leading to the inhibition the activity of the Notch pathway, and ultimately upregulating LUAD cell sensitivity to anti-tumor drugs.

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“…Afatinib, a second-generation tyrosine kinase inhibitor, is an oral irreversible blocker of epidermal growth factor receptor (EGFR) signaling. Preclinical studies show that it is highly selective, irreversibly inhibiting the signaling from several ErbBs, including ErbB1, ErbB2, ErbB3, and ErbB4 [1, 2]. Afatinib is a novel aniline-quinazoline derivative, developed by Boehringer Ingelheim (Ingelheim am Rhein, Germany).…”

Section: Introductionmentioning

confidence: 99%

Determination of Afatinib in Human Plasma by 2-Dimensional Liquid Chromatography

et al. 2022

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Introduction: A simple, sensitive, rapid, and practical 2-dimensional liquid chromatography (2D-LC) method was developed and validated for the quantification of a 500-μL afatinib sample extracted from human plasma. Methods: The plasma samples were pretreated with acetonitrile for protein precipitation. The mobile phase consisted of a first-dimensional mobile phase (acetonitrile, methanol, and 25 mmol/L ammonium phosphate in a ratio of 25:25:50, V/V/V) and a second-dimensional mobile phase (acetonitrile and 10 mmol/L ammonium phosphate in a ratio of 25:75, V/V). The average recovery of the plasma samples was stable and reproducible (98.56%–100.02%). Results: The analyte was sufficiently stable for handling and analysis. The calibration curve was linear, ranging from 10.93 to 277.25 ng/mL with regression equation y = 804.60 x – 4,169.87 (R2 = 0.999). The relative standard deviations for accuracy and precision studies were within ±2.30% and <3.41%, respectively (intra- and interday). Finally, the validated method was successfully employed to determine the drug levels in plasma from the patients treated with afatinib. In clinical assessment, the patients with gastric cancer were orally administered with 30 or 40 mg per day of afatinib, which resulted in large plasma concentrations, ranging from 5.52 to 45.16 ng/mL. Conclusion: The results indicated that this method was useful for the therapeutic drug monitoring of afatinib and suitable for the assessment of the risks and benefits of chemotherapy in patients with non-small cell lung cancer.

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Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer

Cited by 4 publications

References 9 publications

Adverse Reactions of Targeted Therapy in Cancer Patients: A Retrospective Study of Hospital Medical Data in China

Adverse Reactions of Targeted Therapy in Cancer Patients: A Retrospective Study of Hospital Medical Data in China

miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway

Determination of Afatinib in Human Plasma by 2-Dimensional Liquid Chromatography

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