Epidermal growth factor receptor tyrosine kinase inhibitors

表皮生长因子受体酪氨酸激酶抑制剂
  • 文章类型: Case Reports
    背景:表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)可显著提高非小细胞肺癌(NSCLC)表皮生长因子受体(EGFR)敏感突变患者的生存率。
    方法:一名67岁女性晚期肺腺癌患者,在EGFR-TKIs治疗后出现耐药。继发性病理组织活检证实鳞状细胞癌(SCC)转化。患者在接受EGFR-TKIs治疗一定时间后不可避免地遇到耐药问题,而EGFR-TKIs可显著提高EGFR敏感突变NSCLC患者的生存率。值得注意的是,EGFR-TKIs耐药性包括原发性和获得性。病理转化是EGFR-TKIs获得性耐药的机制之一,SCC转化相对罕见。我们的结果提供了患者的诊断和治疗过程中关于肺腺癌EGFR-TKIs治疗后SCC转化的更详细的结果。
    结论:鳞状细胞癌转化是EGFR-TKIs在EGFR突变的晚期肺腺癌中的获得性耐药机制之一。
    BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly improve the survival of patients with Epidermal growth factor receptor (EGFR) sensitive mutations in non-small cell lung cancer (NSCLC).
    METHODS: A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment. Secondary pathological tissue biopsy confirmed squamous cell carcinoma (SCC) transformation. Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time, while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC. Notably, EGFR-TKIs resistance includes primary and acquired. Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs, with SCC transformation being relatively rare. Our results provide more detailed results of the patient\'s diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma.
    CONCLUSIONS: Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    靶向治疗大大改善了肺癌(LC)患者的临床结果,但是获得性耐药和疾病复发不可避免地发生。越来越多,表观遗传机制在驱动获得性耐药中的作用受到赞赏。特别是,N6-甲基腺苷(m6A),最普遍的RNA修饰之一,有几个调节RNA稳定性的作用,拼接,转录,翻译,和毁灭。大量研究表明,m6ARNA甲基化可以调节癌细胞的生长和侵袭,并有助于LC的靶向治疗抗性。在这项研究中,我们概述了已知的m6A在获得LC靶向治疗抵抗方面的功能.
    Targeted therapies have greatly improved clinical outcomes for patients with lung cancer (LC), but acquired drug resistance and disease relapse inevitably occur. Increasingly, the role of epigenetic mechanisms in driving acquired drug resistance is appreciated. In particular, N6-methyladenosine (m6A), one of the most prevalent RNA modifications, has several roles regulating RNA stability, splicing, transcription, translation, and destruction. Numerous studies have demonstrated that m6A RNA methylation can modulate the growth and invasion of cancer cells as well as contribute to targeted therapy resistance in LC. In this study, we outline what is known regarding the function of m6A in the acquisition of targeted therapy resistance in LC.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:在最近的研究中,表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)与抗血管内皮生长因子受体(VEGFR)药物的联合使用已显示出改善的生存结果。然而,其作为一线或二线药物以及基于世代的疗效与生存结局相关仍有待探索.这项研究估计了EGFR-TKIs联合抗VEGFR在确定的晚期非小细胞肺癌(NSCLC)患者人群中的生存结果,作为一线或二线治疗,以不同世代的EGFR-TKIs和EGFR-TKIs联合贝伐单抗为亚组。
    方法:使用PubMed进行了文献检索,Scopus,科克伦图书馆,和截至2023年6月的ClinicalTrials.gov数据库,以确定报告EGFR-TKIs联合抗VEGFR药物在晚期NSCLC患者中的生存结局的主要研究。单臂研究,以非英语语言出版,而缺失的生存结局数据被排除.进行荟萃分析,以产生总生存期(OS)和无进展生存期(PFS)的具有95%置信区间(CI)的合并风险比(HR)。研究中的方法学质量和偏倚风险使用Cochrane手册系统评价偏倚干预风险工具。
    结果:共20项随机对照试验纳入定性综合,11名(2182名参与者)纳入荟萃分析.患者的中位年龄为58至68岁;36%至70%的患者为女性;其中大多数患有IIIa/b至IV期癌症。在荟萃分析中,EGFR-TKIs+抗VEGFR组合导致PFS改善(HR,0.73;95%CI:0.61,0.86;p<0.00001)在晚期非小细胞肺癌患者中,但对OS无影响(HR,0.93;95%CI:0.79,1.10;p=0.41)。一线治疗和第一代EGFR-TKIs联合治疗也改善了PFS(HR,0.64;95%CI:0.57,0.71;p<0.00001;HR,0.63;95%CI:0.56,0.71;p<0.00001),然而,对操作系统没有影响。
    结论:我们的荟萃分析表明,EGFR-TKIs联合抗VEGFR不仅改善了总体PFS,而且与单独使用EGFR-TKI相比,与一线和第一代药物相似。
    BACKGROUND: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in combination with anti-vascular endothelial growth factor receptor (VEGFR) agents have shown improved survival outcomes in recent studies. However, its efficacy related to survival outcomes as a first- or second-line agent and based on generations remains to be explored. This study estimated the survival outcomes of EGFR-TKIs plus anti-VEGFR in combination in defined populations of advanced non-small cell lung cancer (NSCLC) patients overall, as a first- or second line of treatment, with different generations of EGFR-TKIs and EGFR-TKIs plus bevacizumab combination as a subgroup.
    METHODS: A literature search was conducted using PubMed, SCOPUS, Cochrane Library, and ClinicalTrials.gov databases through June 2023 to identify primary research reporting the survival outcomes of EGFR-TKIs in combination with anti-VEGFR agents in patients with advanced NSCLC. Studies that were single-arm, published in non-English languages, and had missing data on survival outcomes were excluded. A meta-analysis was conducted to generate pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS) and progression-free survival (PFS). Methodological quality and risk of bias in studies were assessed using the Cochrane Handbook for Systematic Reviews of Interventions risk of bias tool.
    RESULTS: A total of 20 randomized controlled trials were included in the qualitative synthesis, and 11 (2182 participants) were included in the meta-analysis. Patients\' median age ranged from 58 to 68 years; 36% to 70% of patients were female; most of them had IIIa/b to IV stage cancer. In meta-analyses, the EGFR-TKIs plus anti-VEGFR combination resulted in improved PFS (HR, 0.73; 95% CI: 0.61, 0.86; p < 0.00001) in patients with advanced NSCLC but had no impact on OS (HR, 0.93; 95% CI: 0.79, 1.10; p = 0.41). The first line of treatment and first-generation EGFR-TKIs with the combination also improved the PFS (HR, 0.64; 95% CI: 0.57, 0.71; p < 0.00001; HR, 0.63; 95% CI: 0.56, 0.71; p < 0.00001) respectively, however, had no impact on OS.
    CONCLUSIONS: Our meta-analysis indicated EGFR-TKIs with anti-VEGFR in combination not only improved overall PFS but also showed similar results to a first line and first-generation agent compared to EGFR-TKI alone.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    长链非编码RNAHOTAIR和Hedgehog-Gli1信号通路与多种肿瘤的发生和耐药密切相关。然而,它们在非小细胞癌EGFR-TKIs耐药中的具体作用尚不清楚.为了解决EGFR-TKIs耐药的问题,这项研究利用电喷雾方法制备了封装HOTAIRsiRNA(SA/HOTAIRsiRNA)的海藻酸钠微球,并研究了其对吉非替尼耐药细胞系PC9/GR中RNA干扰(RNAi)的影响。此外,这项研究探讨了HOTAIR是否可以通过Hedgehog-GLi1信号通路调节EGFR-TKIs耐药。结果表明,海藻酸钠(SA)微球具有良好的生物相容性,具有较高的包封率和载药能力,有效提高siRNA的沉默效率。HOTAIRsiRNA显著抑制细胞增殖,迁移,PC9/GR细胞在促进凋亡的同时具有侵袭能力。此外,HOTAIRsiRNA有效抑制肿瘤生长,下调Hedgehog-GLi1通路和抗凋亡蛋白,这在动物实验中得到了证实。此外,与单独使用HOTAIRsiRNA相比,SA/HOTAIRsiRNA表现出对细胞和肿瘤功能的优异抑制。临床研究结果表明,监测NSCLC患者接受EGFR-TKIs治疗前后血清和尿液中HOTAIR的表达水平,可以在一定程度上预测EGFR-TKIs的疗效。这项研究提供了证据,表明HOTAIRsiRNA通过抑制Hedgehog-GLi1途径有效缓解了对EGFR-TKIs的获得性抗性的发展。此外,它引入了一种可靠且持久的药物递送系统,以对抗EGFR-TKIs的获得性耐药。
    The long non-coding RNA HOTAIR and the Hedgehog-Gli1 signaling pathway are closely associated with tumor occurrence and drug resistance in various cancers. However, their specific roles in the development of EGFR-TKIs resistance in non-small cell carcinoma remain unclear. To address the issue of EGFR-TKIs resistance, this study utilized the electrospray method to prepare sodium alginate microspheres encapsulating HOTAIR siRNA (SA/HOTAIR siRNA) and investigated its effects on RNA interference (RNAi) in the gefitinib-resistant cell line PC9/GR. Furthermore, the study explored whether HOTAIR could modulate EGFR-TKIs resistance through the Hedgehog-GLi1 signaling pathway. The experimental results showed that sodium alginate (SA) microspheres demonstrated excellent biocompatibility with high encapsulation efficiency and drug-loading capacity, effectively enhancing the silencing efficiency of siRNA. HOTAIR siRNA significantly inhibited the proliferation, migration, and invasion abilities of PC9/GR cells while promoting apoptosis. Additionally, HOTAIR siRNA effectively suppressed tumor growth and downregulated the Hedgehog-GLi1 pathway and anti-apoptotic proteins, which were confirmed in animal experiments. Moreover, SA/HOTAIR siRNA exhibited superior inhibition of cellular and tumor functions compared to using HOTAIR siRNA alone. Clinical research findings indicated that monitoring the expression level of HOTAIR in the serum and urine samples of NSCLC patients before and after receiving EGFR-TKIs treatment can predict the efficacy of EGFR-TKIs to a certain extent. This study provided evidence that HOTAIR siRNA effectively mitigated the development of acquired resistance to EGFR-TKIs by inhibiting the Hedgehog-GLi1 pathway. Furthermore, it introduced a reliable and long-lasting drug delivery system for combating acquired resistance to EGFR-TKIs.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    Non-small cell lung cancer (NSCLC) is one of the most devastating cancers with a high incidence and mortality rates of all cancers. Locally advanced or metastatic NSCLC patients can benefit from platinum-based chemotherapy and targeted therapy drugs. Nevertheless, primary or acquired drug resistance will result in ineffective treatment, leading to tumor progression. The detailed mechanism underlying drug resistance to NSCLC are complicated and result from various factor. Among them, long noncoding RNAs (lncRNAs) have been found to be critically involved in NSCLC development and play a vital role in mediating therapy resistance. In this review, we attempt to systematically summarize the mechanisms underlying the lncRNA-mediated resistance to chemotherapy agents and targeted therapy drugs against lung cancer.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    据报道,老年晚期非小细胞肺癌(NSCLC)患者使用奥希替尼后出现长QT综合征(LQTS),第三代表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKI)。然而,目前还没有关于这一主题的流行病学分析研究。我们旨在比较老年晚期NSCLC患者中奥希替尼和第一代/第二代EGFR-TKIs的LQTS风险。
    这项回顾性观察研究使用了2006-2019年的监测,流行病学,和最终结果(SEER)-Medicare数据,包括2007-2017年期间接受奥希替尼或第一代/第二代EGFR-TKIs治疗的老年晚期NSCLC患者。使用治疗权重的逆概率(IPTW)来平衡两组患者的社会经济和临床特征所估计的倾向评分。主要结局的粗发生率(IR)和调整后的风险比(HR),事件LQTS,估计。
    共有545名和1,135名患者被纳入奥希替尼和第一代/第二代EGFR-TKI组,分别增加到1,614和1,659,在IPTW之后。奥希替尼组的LQTSIR较高(2.62/100人年,95%CI2.03-3.38)与第一代/第二代EGFR-TKI组(每100人年1.33,95%CI0.92-1.92)。在调整协变量后,奥希替尼组的LQTS风险高于第一代/第二代EGFR-TKI组,HR为1.94(95%CI1.23-3.08)。奥希替尼组LQTS风险增加的女性甚至更高,白人和年龄≥75岁的患者。
    鉴于与奥希替尼使用者相关的LQTS风险升高,我们建议在EGFR-TKI开始治疗后密切监测高危患者的心律异常.
    长QT综合征(LQTS)表示QT间期延长的心跳障碍。有报道称,接受奥希替尼治疗的老年晚期非小细胞肺癌(NSCLC)患者存在LQTS,第三代表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKI)。我们进行了一项回顾性研究,使用监测,流行病学,和最终结果(SEER)-医疗保险数据库,包括接受EGFR-TKIs治疗的年龄≥65岁的晚期NSCLC患者。我们的结果显示,使用奥希替尼后LQTS的发生率高于第一代/第二代EGFR-TKIs。在调整了可能影响LQTS发生率的患者特征后,奥希替尼使用者的LQTS风险显著高于前一代EGFR-TKI使用者.雌性,白人,年龄≥75岁的患者接受奥希替尼治疗时,LQTS的风险更高.建议密切监测奥希替尼开始后高危患者的心律异常。
    UNASSIGNED: Long QT syndrome (LQTS) has been reported in older patients with advanced non-small cell lung cancer (NSCLC) following the use of osimertinib, the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). However, there have not been analytic epidemiology studies on this topic. We aimed to compare the risk of LQTS between osimertinib and first/second-generation EGFR-TKIs in older patients with advanced NSCLC.
    UNASSIGNED: This retrospective observational study used the 2006-2019 Surveillance, Epidemiology, and End Results (SEER)-Medicare data and included older patients with advanced NSCLC who were treated with either osimertinib or first/second-generation EGFR-TKIs during 2007-2017. Inverse probability of treatment weighting (IPTW) was used to balance the two groups with propensity scores estimated based on the patients\' socioeconomic and clinical characteristics. Crude incidence rate (IR) and adjusted hazard ratio (HR) of the primary outcome, incident LQTS, were estimated.
    UNASSIGNED: A total of 545 and 1,135 patients were included in the osimertinib and first/second-generation EGFR-TKI groups, which increased to 1,614 and 1,659, respectively, after IPTW. The osimertinib group had a higher IR of LQTS (2.62 per 100 person-years, 95% CI 2.03-3.38) compared to the first/second-generation EGFR-TKI group (1.33 per 100 person-years, 95% CI 0.92-1.92). After adjusting for covariates, the osimertinib group had a higher risk of LQTS than the first/second-generation EGFR-TKI group, with an HR of 1.94 (95% CI 1.23-3.08). The increased LQTS risk in the osimertinib group was even higher in females, whites and patients aged ≥ 75.
    UNASSIGNED: Given the elevated risk of LQTS associated with osimertinib user, close monitoring for cardiac rhythm irregularities of high-risk patients following initiation of EGFR-TKI is recommended.
    Long QT syndrome (LQTS) indicates a disorder of heart beats with prolonged QT intervals. There have been reports of LQTS in older patients with advanced non-small cell lung cancer (NSCLC) who were treated with osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). We conducted a retrospective study using Surveillance, Epidemiology, and End Results (SEER)-Medicare database, including older patients aged ≥ 65 with advanced NSCLC who were treated with EGFR-TKIs. Our results show higher incidence of LQTS after using osimertinib than first/second-generation EGFR-TKIs. After adjusting for patients’ characteristics that might have affected the incidence of LQTS, the risk of LQTS was significantly higher in osimertinib users than in earlier generation EGFR-TKI users. Females, whites, and patients aged ≥ 75 had an even higher risk of LQTS when treated with osimertinib. Close monitoring for cardiac rhythm irregularities in high-risk patients after osimertinib initiation is recommended.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Meta-Analysis
    背景:对于新诊断的EGFR突变的非小细胞肺癌脑转移瘤(BMs),前期脑放疗(RT)联合表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)的一线治疗是否优于单独的EGFR-TKIs。因此,我们进行了荟萃分析来解决这个问题.
    方法:我们搜索了PubMed,Embase,科克伦图书馆,和WebofScience数据库,用于在2023年2月28日之前发布的合格研究。感兴趣的主要结果是总生存期(OS)和颅内无进展生存期(iPFS),报告为风险比(HR)和95%置信区间(CI)。
    结果:纳入了24项回顾性研究,共3184例患者。在每个研究中使用第一代或第二代EGFR-TKIs。与单独使用EGFR-TKIs相比,前期脑RT加EGFR-TKIs显着延长OS(HR=0.75,95%CI:0.64-0.88)和iPFS(HR=0.61,95%CI:0.52-0.72)。在无症状和有症状患者之间,联合治疗的OS和iPFS获益没有显着差异。有外显子19和21突变的患者,1-3和>3个BMs的患者,男性和女性,分别(HR相互作用,各亚组比较P>0.05)。
    结论:一线治疗前脑RT+EGFR-TKIs可能比单独使用EGFR-TKIs更有效。联合治疗的益处似乎没有受到BM相关症状的显著影响,EGFR突变亚型,BMS的数量,或性。
    BACKGROUND: It remains uncertain whether first-line treatment with upfront brain radiotherapy (RT) in combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is superior to EGFR-TKIs alone for EGFR-mutated non-small cell lung cancer with newly diagnosed brain metastases (BMs). Therefore, we performed a meta-analysis to address this issue.
    METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science databases for eligible studies published until February 28, 2023. The primary outcomes of interest were overall survival (OS) and intracranial progression-free survival (iPFS), reported as hazard ratios (HRs) and 95% confidence intervals (CIs).
    RESULTS: Twenty-four retrospective studies with 3184 patients were included. First- or second-generation EGFR-TKIs were used in each study. Upfront brain RT plus EGFR-TKIs significantly prolonged OS (HR = 0.75, 95% CI: 0.64-0.88) and iPFS (HR = 0.61, 95% CI: 0.52-0.72) compared to EGFR-TKIs alone. There were no significant differences in OS and iPFS benefits from the combination therapy between asymptomatic and symptomatic patients, patients with exon 19 and 21 mutations, patients with 1-3 and > 3 BMs, and males and females, respectively (HRs interaction, P > 0.05 for each subgroup comparison).
    CONCLUSIONS: First-line treatment with upfront brain RT plus EGFR-TKIs is likely to be more effective than EGFR-TKIs alone. The benefits of combination therapy did not appear to be significantly affected by BM-related symptoms, EGFR mutation subtype, number of BMs, or sex.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    严重腹泻是表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)的常见副作用。我们旨在使用人和猴隐窝来源的肠干细胞的球体评估EGFR-TKI诱导的腹泻的风险。肠球体对EGFR-TKIs的毒性敏感性高于Caco-2细胞。随着EGFR-TKIs浓度的增加,细胞ATP首先相对于对照条件降低,其次是LDH释放的增加,与它们与传统细胞毒性抗癌药物的同时变化相反。球体对各种EGFR-TKIs的毒性敏感性与临床腹泻发生率相对应。阿法替尼,第二代EGFR-TKI,与第一代相比,表现出更高的毒性敏感性,与阿法替尼引起的腹泻几乎不可避免且严重的临床证据相对应。相比之下,第三代奥希替尼,这降低了腹泻的风险,与阿法替尼相比,细胞毒性减轻。对于不可逆的EGFR-TKIs,与可逆药物相比,药物去除后降低的ATP水平恢复不佳或延迟。此外,阿法替尼在球体中的药物累积量最高(TKIsphoides)和对EGFR的抑制效力最高(TKIsphoides/Ki).该系统将有助于预测EGFR-TKI引起的腹泻的风险;此外,针对肠干细胞的靶向细胞毒性可能导致临床观察到的腹泻。
    Severe diarrhea is a common side effect of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). We aimed to evaluate the risk of EGFR-TKI-induced diarrhea using spheroids of human and monkey crypt-derived intestinal stem cells. Intestinal spheroids exhibited higher toxic susceptibility to EGFR-TKIs than Caco-2 cells. As concentration of EGFR-TKIs increased, cellular ATP first decreased relative to the control condition, followed by an increase in LDH release, in contrast with their simultaneous changes with traditional cytotoxic anticancer drugs. The toxic sensitivity of spheroids to various EGFR-TKIs corresponded to clinical diarrhea incidence. Afatinib, a second-generation EGFR-TKI, exhibited higher toxic sensitivity compared with the first-generation ones, corresponding to the clinical evidence that afatinib-induced diarrhea is almost inevitable and severe. By contrast, the third-generation osimertinib, which reduces the risk of diarrhea, showed mitigated cytotoxicity compared with afatinib. For irreversible EGFR-TKIs, the decreased ATP level persisted or its recovery was delayed even after drug removal compared with reversible ones. Furthermore, the highest drug accumulation in spheroids (TKIspheroids) and inhibition potency against EGFR (TKIspheroids/Ki) were observed for afatinib. This system would be useful for predicting the risk of EGFR-TKI-induced diarrhea; moreover, on-target cytotoxicity against intestinal stem cells might contribute to clinically observed diarrhea.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    暂无摘要。
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    非癌性药物目前正被重新用于癌症治疗。越来越多的证据强调了钙通道对肿瘤发生和进展的影响。因此,抑制钙信号可能是一种有前途的癌症治疗策略。
    在这项研究中,我们旨在研究钙通道阻滞剂(CCBs)是否影响表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)治疗非小细胞肺癌(NSCLC)的疗效.
    我们进行了回顾性分析。
    在这项研究中,2009年1月至2021年6月,接受厄洛替尼治疗的NSCLC患者,或吉非替尼至少1周,分为2组:CCBS-/EGFR-TKIs+和CCBs+/EGFR-TKIs+,取决于他们是否接受CCB治疗。无进展生存期(PFS)和总生存期(OS)被确定为主要和次要终点,分别。
    结果::CCBS-/EGFR-TKIs+组的估计中位PFS和OS分别为7.70和12.17个月,分别,它们与CCBs+/EGFR-TKIs+组(10.43和18.07个月,分别)。CCB使用与改善的PFS(调整后的风险比[HR]0.77,95%置信区间[CI]:0.61-0.98;P=0.035)和OS(调整后的HR0.66,95%CI:0.51-0.84;P<.001)相关。
    钙通道与癌症的发病机制有关。我们的发现揭示了CCB与EGFR-TKIs同时使用时的潜在累加抗癌作用。然而,研究局限性,包括回顾性和少数患者,有必要对CCB作为EGFR-TKIs辅助治疗NSCLC患者的治疗潜力进行大规模前瞻性研究。
    Non-cancer drugs are currently being repurposed for cancer treatment. Mounting evidence highlights the influence of calcium channels on tumorigenesis and progression. Hence, inhibition of calcium signaling may be a promising cancer treatment strategy.
    In this study, we aimed to examine whether calcium channel blockers (CCBs) affect the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung cancer (NSCLC).
    We conducted a retrospective analysis.
    In this study, conducted between January 2009 and June 2021, patients with NSCLC treated with erlotinib, or gefitinib for at least 1 week were enrolled and divided into 2 groups: CCBs-/EGFR-TKIs+ and CCBs+/EGFR-TKIs+, depending on whether they received CCB therapy. Progression-free survival (PFS) and overall survival (OS) were determined as the primary and secondary endpoints, respectively.
    : The estimated median PFS and OS for the CCBs-/EGFR-TKIs+group were 7.70 and 12.17 months, respectively, and they were significantly different from those of the CCBs+/EGFR-TKIs+ group (10.43 and 18.07 months, respectively). CCB use was associated with improved PFS (adjusted hazard ratios [HR] 0.77, 95% confidence interval [CI]: 0.61-0.98; P = .035) and OS (adjusted HR 0.66, 95% CI: 0.51-0.84; P < .001).
    Calcium channels have been implicated in cancer pathogenesis. Our findings revealed the potential additive anticancer effects of CCBs when used concomitantly with EGFR-TKIs. However, study limitations, including the retrospective nature and small number of patients, necessitate large-scale prospective studies on the therapeutic potential of CCB as an adjunctive therapy with EGFR-TKIs in patients with NSCLC.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

公众号