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Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer.


  • 影响因子:0
  • DOI:10.1002/14651858.CD009256.pub3
  • 作者列表:"Vasconcellos VF","Marta GN","da Silva EM","Gois AF","de Castria TB","Riera R
  • 发表时间:2020-01-13

BACKGROUND:Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in both sexes worldwide. Approximately 50% of those diagnosed with lung cancer will have locally advanced or metastatic disease and will be treated in a palliative setting. Platinum-based combination chemotherapy has benefits in terms of survival and symptom control when compared with best supportive care. OBJECTIVES:To assess the effectiveness and safety of carboplatin-based chemotherapy when compared with cisplatin-based chemotherapy, both in combination with a third-generation drug, in people with advanced non-small cell lung cancer (NSCLC). To compare quality of life in people with advanced NSCLC receiving chemotherapy with cisplatin and carboplatin combined with a third-generation drug. SEARCH METHODS:We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 13 January 2019), MEDLINE (via PubMed) (1966 to 13 January 2019), and Embase (via Ovid) (1974 to 13 January 2019). In addition, we handsearched the proceedings of the American Society of Clinical Oncology Meetings (January 1990 to September 2018) and reference lists from relevant resources. SELECTION CRITERIA:Randomised clinical trials (RCTs) comparing regimens with carboplatin or cisplatin combined with a third-generation drug in people with locally advanced or metastatic NSCLC. We accepted any regimen and number of cycles that included these drugs, since there is no widely accepted standard regimen. DATA COLLECTION AND ANALYSIS:Two review authors independently assessed the search results, and a third review author resolved any disagreements. The primary outcomes were overall survival and health-related quality of life. The secondary outcomes were one-year survival rate, objective response rate and toxicity. MAIN RESULTS:In this updated review, we located one additional RCT, for a total of 11 included RCTs (5088 participants, 4046 of whom were available for meta-analysis). There was no difference in overall survival (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.82 to 1.20; 10 RCTs; 2515 participants; high-quality evidence); one-year survival rate (risk ratio (RR) 0.98, 95% CI 0.89 to 1.08; I2 = 17%; 4004 participants; all 11 RCTs; high-quality evidence); or response rate (RR 0.89, 95% CI 0.79 to 1.00; I2 = 12%; all 11 RCTs; 4020 participants; high-quality evidence). A subgroup analysis comparing carboplatin with different doses of cisplatin found an overall survival benefit in favour of carboplatin-based regimens when compared to cisplatin at lower doses (40 to 80 mg/m2) (HR 1.15, 95% CI 1.03 to 1.28; 6 RCTs; 2508 participants), although there was no overall survival benefit when carboplatin-based chemotherapy was compared to cisplatin at higher doses (80 to 100 mg/m2) (HR 0.93, 95% CI 0.83 to 1.04; I2 = 0%; 4 RCTs; 1823 participants). Carboplatin caused more thrombocytopenia (RR 2.46, 95% CI 1.49 to 4.04; I2 = 68%; 10 RCTs; 3670 participants) and was associated with more neurotoxicity (RR 1.42, 95% CI 0.91 to 2.23; I2 = 0%, 5 RCTs; 1489 participants), although we believe this last finding is probably related to a confounding factor (higher dose of paclitaxel in the carboplatin-containing treatment arm of a large study included in the analysis). There was no statistically significant difference in renal toxicity (RR 0.52, 95% CI 0.19 to 1.45; I2 = 3%; 3 RCTs; 1272 participants); alopecia (RR 1.11, 95% CI 0.73 to 1.68; I2 = 0%; 2 RCTs; 300 participants); anaemia (RR 1.37, 95% CI 0.79 to 2.38; I2 = 77%; 10 RCTs; 3857 participants); and neutropenia (RR 1.18, 95% CI 0.85 to 1.63; I2 = 94%; 10 RCTs; 3857 participants) between cisplatin-based chemotherapy and carboplatin-based chemotherapy regimens. Two RCTs performed a health-related quality of life analysis; however, as they used different methods of measurement we were unable to perform a meta-analysis. One RCT reported comparative health-related quality of life data between cisplatin and carboplatin-containing arms but found no significant differences in global indices of quality of life, including global health status or functional scales. In this Cochrane review, we found that the quality of evidence was high for overall survival, one-year survival rate and response rate but moderate quality evidence for the other outcomes measured. AUTHORS' CONCLUSIONS:Advanced NSCL patients treated with carboplatin or cisplatin doublet with third-generation chemotherapy drugs showed equivalent overall survival, one-year survival, and response rate. Regarding adverse events, carboplatin caused more thrombocytopenia, and cisplatin caused more nausea/vomiting. Therefore, in this palliative therapeutic intent, the choice of the platin compound should take into account the expected toxicity profile, patient's comorbidities and preferences.


背景: 肺癌是世界上最常见的癌症,也是两性癌症死亡的主要原因。大约 50% 被诊断患有肺癌的患者将具有局部晚期或转移性疾病,并且将在姑息性环境中治疗。与最佳支持治疗相比,基于铂的联合化疗在生存和症状控制方面具有益处。 目的: 评估以卡铂为基础的化疗与以顺铂为基础的化疗相比的有效性和安全性,在晚期非小细胞肺癌 (NSCLC) 患者中。比较接受顺铂和卡铂联合第三代药物化疗的晚期NSCLC患者的生活质量。 检索方法: 我们检索了以下电子数据库: Cochrane中央对照试验注册中心 (Central; 2019 年 1 月 13 日),MEDLINE (通过PubMed) (1966 至 2019 年 1 月 13 日),和Embase (通过Ovid) (1974 至 2019 年 1 月 13 日)。此外,我们还手工检索了美国临床肿瘤学会会议记录 (1990 年 1 月至 2018 年 9 月) 和相关资源的参考文献。 选择标准: 比较卡铂或顺铂联合第三代药物治疗局部晚期或转移性NSCLC患者的随机临床试验 (RCTs)。我们接受包括这些药物的任何方案和周期数,因为没有广泛接受的标准方案。 数据收集和分析: 两位评论作者独立评估了搜索结果,第三位评论作者解决了任何分歧。主要结局为总生存期和健康相关生活质量。次要结局为 1 年生存率、客观缓解率和毒性反应。 主要结果: 在这篇更新的综述中,我们找到了一个额外的RCT,总共 11 个纳入的RCT (5088 名参与者,其中 4046 名可用于荟萃分析)。总生存期无差异 (风险比 (HR) 0.99,95% 置信区间 (CI) 0.82 至 1.20; 10 个rct; 2515 名参与者; 高质量证据); 1 年生存率 (风险比 (RR) 0.98,95% CI 0.89 至 1.08; I2 = 17%; 4004 参与者;所有 11 项rct; 高质量证据); or缓解率 (RR 0.89,95% CI 0.79 至 1.00; I2 = 12%; 所有 11 项rct; 4020 名参与者; 高质量证据)。比较卡铂与不同剂量顺铂的亚组分析发现,与低剂量顺铂 (40 至 80 mg/m2) 相比,卡铂为基础的方案总体生存获益 (HR 1.15,95% CI 1.03 to 1.28; 6 个rct; 2508 名参与者),尽管以卡铂为基础的化疗与顺铂高剂量 (80 ~ 100 mg/m2) 相比没有总体生存获益 (HR 0.93,95% CI 0.83 ~ 1.04); i2 = 0%; 4 个rct; 1823 名参与者)。卡铂导致更多的血小板减少症 (RR 2.46,95% CI 1.49 至 4.04; I2 = 68%; 10 个rct; 3670 名参与者),并与更多的神经毒性相关 (RR 1.42,95% CI 0.91 至 2.23; i2 = 0%,5 个rct; 1489 名参与者),虽然我们认为这最后的发现可能与一个混杂因素有关 (一项大型研究中包含卡铂的治疗组中较高剂量的紫杉醇)。肾毒性差异无统计学意义 (RR 0.52,95% CI 0.19 ~ 1.45; I2 = 3%; 3 个rct; 1272 名参与者); 脱发 (RR 1.11,95% CI 0.73 至 1.68; I2 = 0%; 2 个rct; 300 名参与者); 贫血 (RR 1.37,95% CI 0.79 至 2.38; I2 = 77%; 10 个rct; 3857 名参与者); 和中性粒细胞减少症 (RR 1.18,95% CI 0.85 至 1.63; I2 = 94%; 10 个rct; 3857 名参与者) 基于顺铂的化疗方案和基于卡铂的化疗方案之间。两项rct进行了健康相关的生活质量分析; 然而,由于他们使用不同的测量方法,我们无法进行荟萃分析。一项RCT报告了顺铂和含卡铂武器之间的健康相关生活质量比较数据,但发现全球生活质量指数 (包括全球健康状况或功能量表) 没有显著差异。在这项Cochrane综述中,我们发现总体生存率、 1 年生存率和缓解率的证据质量很高,但其他测量结果的证据质量适中。 作者的结论: 晚期NSCL患者接受卡铂或顺铂双重第三代化疗药物治疗显示了相当的总生存率,一年生存率和缓解率。关于不良事件,卡铂引起更多的血小板减少,顺铂引起更多的恶心/呕吐。因此,在这种姑息治疗意图中,铂化合物的选择应考虑预期的毒性特征、患者的合并症和偏好。



作者列表:["Mammana M","Zuin A","Serra E","Bellini A","Rea F"]

METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.

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作者列表:["Hata A","Nakajima T","Matsusaka K","Fukuyo M","Morimoto J","Yamamoto T","Sakairi Y","Rahmutulla B","Ota S","Wada H","Suzuki H","Matsubara H","Yoshino I","Kaneda A"]

METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.

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作者列表:["Zhang L","Yang Y","Chai L","Bu H","Yang Y","Huang H","Ran J","Zhu Y","Li L","Chen F","Li W"]

METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.

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