ZD1839（Iressa）在晚期非小细胞肺癌治疗中的应用

目的　探讨表皮生长因子受体酪氨酸激酶抑制剂———ZD183 9(Iressa)治疗晚期非小细胞肺癌的疗效和毒副反应。方法　分析 2 0 0 2年 12月至 2 0 0 3年 8月期间我院 3 9例晚期非小细胞肺癌患者经ZD183 92 5 0mg/d口服治疗的情况。应用 χ2 检验、t检验、Kaplan Meier进行统计分析。并采用欧洲癌症研究和治疗组织 (EuropeanOrganizationforResearchandTreatmentofCancer ,EORTC)简体中文版的生活质量调查核心问卷QLQ C3 0和肺癌专用问卷QLQ LC13对患者的生活质量进行评价。结果　全组患者有效率 (完全缓解 +部分缓解 )为 2 8.2 %,疾病控制率 (有效 +稳定 )为 5 9.0 %。疗效与患者性别和病理类型有密切关系。综合生活质量改善率为 3 4.8%,功能状态改善率为 65 .2 %,临床症状缓解率为 73 .9%。全组无疾病进展时间为 6.6月± 1.6月 ( 95 %CI为 3 .4～ 9.7) ,到截尾时间 5 6.4%( 2 2 /3 9)的患者仍存活 ,1年生存率为 5 4.3 %( 19/3 5 )。毒副反应主要为Ⅰ、Ⅱ度皮疹和腹泻 ,经对症处理可缓解。结论　ZD183 9治疗晚期非小细胞肺癌疗效确切 ,同时可改善生活质量     

Nouvelle perspective de traitement dans le cancer bronchique non à petites cellules (CBNPC). Place de l’afatinib : un inhibiteur oral et irréversible de la famille ErbB

Tyrosine kinase inhibitors (TKI) that block epidermal growth factor receptor (EGFR) pathway have demonstrated a clinical benefit for patients with non-small-cell lung cancer (NSCLC) harboring EGFR mutations. The currently available TKI (gefitinib and erlotinib) are EGFR reversible inhibitors. Afatinib is an oral, irreversible ErbB family blocker that covalently binds and blocks signaling from EGFR (ErbB1), HER2 (ErbB2) and ErbB4. The compound inhibits also the transphosphorylation of ErbB3. With this mode of action, afatinib is thought to have a mechanistic advantage over EGFR blockade alone, in that it provides a sustained, covalent inhibition of ErbB homo- and hetero-dimers. In the pivotal LUX-Lung 3 study, afatinib demonstrated a prolonged progression free survival over standard pemetrexed plus cisplatin chemotherapy (11.1 versus 6.9 months; HR = 0.58, 95% CI: 0.43–0.78; P = 0.001) in EGFR mutation positive NSCLC patients. The compound has recently been granted a marketing authorization (MA) for the treatment of patients with locally advanced or metastatic NSCLC with activating EGFR mutation(s) and EGFR TKI-naive. In this paper are summarized the efficacy and safety data in this indication.     

Progrès dans les traitements des cancers du rein

Partial nephrectomy is the gold standard for the renal tumours less than 7 to 10 cm whenever feasible in order to preserve renal function. The extension of nephron-sparing surgery using a mini-invasive approach is possible by robotic surgery. Radical nephrectomy is mandatory in the other situations and especially in case of locally advanced renal carcinoma. The place of cytoreductive nephrectomy in metastatic renal cell carcinoma is the purpose of the CARMENA trial. Tyrosine kinase inhibitors are currently the first line treatment; but in the near future new immunotherapy by checkpoints molecules could crucially change the treatment of metastatic renal cell carcinoma. Numerous trials in a neoadjuvant or adjuvant settings are ongoing.     

The second annual symposium on the future of lung cancer: a translational focus

Lung cancer continues to be a leading cause of death in the US, and in its most advanced stages remains incurable. Cytotoxic chemotherapies have been the standard of care for the treatment of unresectable disease. However, recent advances in the development of epidermal growth factor receptor (EGFR) inhibitors have led the way to a new generation of targeted biological agents. During the second annual symposium entitled ‘the future of lung cancer: a translational focus’, which was sponsored by the Physician´s Education Resource, new strategies for the treatment of lung cancer were discussed. Besides the role of EGFR inhibitors, potential targets include the angiogenesis pathway; other growth factor pathways, such as phosphoinositol-3 kinase/Akt and Raf-MEK; the 26S proteasome, the histone deacetylase mechanism; and the TNF-related apoptosis-inducing factor receptors. Agents that are directed against these targets are all in varying stages of clinical development. As more is learned about their mechanisms of action and clinical spectrum of activity, the author anticipates their incorporation into novel regimens with enhanced activity against lung cancer.     

Anlotinib,a novel TKI,as a third-line or further-line treatment in patients with advanced non-small cell lung cancer in China: A systemic review and meta-analysis of its efficacy and safety

Purpose:In this meta-analysis and systemic review, we focused on the effectiveness and safety of anlotinib in patients with advanced non-small cell lung cancer(NSCLC).Methods:The databases of PubMed, EMBASE, Cochrane Library, CNKI, Wanfang, and CBM were searched by 2 investigators up to April 2020. Titles and abstracts of all records were screened and eligible publications were retrieved in full. Review Manager (version 5.2, Cochrane Library) was used for data analysis. The outcomes of interest were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse event (TRAE). Data was pooled for quantitative analysis and the effect size was reported as hazard ratio for survival outcomes and odds ratio (OR) for safety outcomes, both with a random-effects model.Results:A sum of 1480 patients were included in 11 trials ranging from 2018 to 2020. Substantial improvements of PFS, OS, and DCR were observed in patients treated with anlotinib alone or in combination with other conventional treatment. Accompanied TRAE included statistically significant higher risk for hypertension (OR = 11.05, 95% confidence interval [CI] = 7.85–15.55, P < .001), hepatic dysfunction (OR = 1.96, 95% CI = 1.29–2.68, P < .001), diarrhea (OR = 2.20, 95% CI = 1.17–4.16, P < .05), and hemoptysis (OR = 2.59, 95% CI = 1.71–3.93, P < .01).Conclusions:Our study suggested that anlotinib as maintenance therapy for advanced NSCLC patients is associated with prolonged PFS and OS as well as DCR improvement, but it was accompanied by increased risk of TRAE, such as hypertension, hepatic dysfunction, diarrhea and hemoptysis. Although much effort has been made to clinical trials of anlotinib, further studies are warranted to provide more convincing evidence.     

A comprehensive review on Brigatinib – A wonder drug for targeted cancer therapy in non-small cell lung cancer

The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90?mg of brigatinib for 7?days and then 180?mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need.     

Targeting PI3K/AKT/mTOR pathway in non small cell lung cancer

While PI3K/AKT/mTOR pathway is altered in a variety of cancers including non small cell lung cancer, abnormalities in this pathway are more common in squamous cell lung carcinoma than in adenocarcinoma of the lung. Moreover, aberrant activation of PI3K/AKT/mTOR pathway is one of the mechanisms of acquired resistance to EGFR-TK inhibitors in patients with adenocarcinoma carrying EGFR activating mutations.