Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report

BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.

Missing the Target?—Targeted Therapy in Small Cell Lung Cancer

Small cell lung cancer [SCLC] is a devastating form of cancer, with most patients harbouring extensive disease at diagnosis and survival of less than 5% at five years. Progress in novel therapies has been limited. This specialist review explores current targeted therapy options and potential areas of development.

Advances in research on targeted therapy for small cell lung cancer

Small cell lung cancer (SCLC) is a kind of pulmonary neuroendocrine tumor with high malignancy,rapid progression and poor prognosis.It accounts for 15% to 20% of the total number of lung cancers.Although radiotherapy and chemotherapy are better for early treatment of small cell lung cancer,they are prone to cell resistance and are prone to metastasis.With the development of targeted therapies in medical history,targeted therapies for SCLC have also received increasing attention.This article summarizes the research progress of targeted therapy in small cell lung cancer in recent years.

Treatment of non-small cell lung cancer in the era of targeted therapy

Lung cancer, mostly non-small cell carcinoma (NSCLC), is still a major global problem with devastating outcomes. The majority presents at late stages, in which the chance of cure is minimal. With the better understanding of lung cancer biology, there have been several novel targeted approaches against NSCLC. Anti-angiogenesis has been proven to be an important approach in combination with systemic chemotherapy treatment in NSCLC at the first-line setting. The prototypic monoclonal antibody against vascular endothelial growth factor (VEGF), be- vacizumab, is now approved for clinical use in combination with platinum-based chemotherapy in first-line treatment of advanced non-squamous NSCLC, associated with improved response and survival compared with chemotherapy alone. The most notable example of targeted therapy for lung cancer is epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI). There have been extensive evidences supporting the superiority of EGFR TKI (like gefitinib or erlotinib) over standard platinum-based doublet chemotherapy in first-line treatment of advanced NSCLC carrying EGFR activating mutations. Almost following the same path as EGFR TKI, a novel target (anaplastic lymphoma kinase, ALK) has been identified recently with a very promising targeted agent (crizotinib) that has already been approved for clinical use in NSCLC carrying ALK rearrangements. Over the past decade, there have been undoubtedly growing armamentaria in the treatment of NSCLC, focusing on personalized and targeted approach.

Clinical characteristics and response to tyrosine kinase inhibitors of patients with non-small cell lung cancer harboring uncommon epidermal growth factor receptor mutations

Objective： To investigate the clinical features of patients with non-small cell lung cancer（NSCLC） harboring uncommon epidermal growth factor receptor（EGFR） mutations, and the treatment outcomes of EGFR tyrosine kinase inhibitors（TKIs） in these patients.Methods： We retrospectively analyzed the data of 128 NSCLC patients pathologically diagnosed with uncommon EGFR mutation in the Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences ＆ Peking Union Medical College and Beijing Hospital from January 2010 to December 2015, including 40 advanced patients who received EGFR-TKI.Results： Among the total 128 patients, 11 patients were non-adenocarcinoma, including squamous carcinoma（3.9%）, adenosquamous carcinoma（2.3%）, large cell carcinoma（0.8%）, and composite neuroendocrine carcinoma（1.6%）. Single mutations accounted for 75.0%（96/128）, including G719X（29.7%）, S768I（18.0%）, 20 exon insertion（13.3%）, L861Q（12.5%）, De novo T790M（0.8%）, and T725（0.8%）. Thirty-two patients harbored complex mutations. Forty advanced patients received EGFR-TKI, the objective response rate（ORR） was 20.0%,the disease control rate（DCR） was 85.0%, and the progression-free survival（PFS） was 6.4 [95% confidence interval（95% CI）, 4.8–7.9] months. The exploratory analysis of tumor response and PFS in 33 patients with G719X/S768I/L861 Q subtypes showed that ORR was 21.2%（7/33）, the DCR was 93.9%（31/33）, and PFS was 7.6（95% CI, 5.8–9.4） months. Patients with exon 20 insertion mutation and De novo T790 M experienced rapid disease progression with PFS no more than 2.7 months.Conclusions： Uncommon EGFR-mutant NSCLCs are heterogeneous, EGFR-TKIs can have different efficacy in this specific subtype, and thus further individual assessment is required for each case.

Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer

Objective： To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer （NSCLC）. Methods： A total of 89 patients with stage IIIB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. Results： A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate （RR） was 36.0% （32/89）, and the disease control rate （DCR） was 69.7% （62/89）. RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma （P〈0.05）. The symptom improvement rate was 57.3% （51/89）, and the main symptoms improved were cough, pain, chest distress, dyspnea, and Eastern Cooperative Oncology Group performance status. The main toxic effects were rash [30/89 （33.7%）] and diarrhea [15/89 （16.9%）]. The level of toxicity was typically low. Conclusions： The use of icofinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.

Review of the current targeted therapies for non-small-cell lung cancer

The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer(NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor(EGFR), and crizotinib which targets anaplastic lymphoma kinase(ALK). We discuss the challenge of acquired resistance to these small-molecular tyrosine kinase inhibitors and review promising agents which may overcome resistance, including the EGFR T790 Mtargeted agents CO-1686 and AZD9291, and the ALKtargeted agents ceritinib(LDK378), AP26113, alectinib(CH/RO5424802), and others. Emerging therapies directed against other driver oncogenes in NSCLC including ROS1, HER2, and BRAF are covered as well. The identification of specific molecular targets in a significant fraction of NSCLC has led to the personalized deployment of many effective targeted therapies, with more to come.

Targeted therapies in epithelial ovarian cancer: Molecular mechanisms of action

Ovarian cancer is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage and have a poor prognosis.Currently, surgical tumor debulking, followed by platinum- and taxane-based chemotherapy is the standard treatment for advanced ovarian cancer. However, these patients are at great risk of recurrence and emerging drug resistance. Therefore, novel treatment strategies are required to improve outcomes for women with advanced ovarian cancer. A variety of molecular targeted agents, the majority of which are monoclonal antibodies and small-molecule protein-kinase inhibitors, have been explored in the management of ovarian cancer. The targets of these agents include angiogenesis, the human epidermal growth factor receptor family, ubiquitinproteasome pathway, epigenetic modulators, poly(ADPribose) polymerase (PARP), and mammalian target of rapamycin (mTOR) signaling pathway, which are aberrant in tumor tissue. The antiangiogenic agent, bevacizumab, has been reported as the most effective targeted agent and should be included in the standard chemotherapeutic regimen for advanced ovarian cancer. PARP inhibitors, which are mainly used in breast and ovarian cancer susceptibility gene-mutated patients, and mTOR inhibitors are also attractive treatment strategies, either alone or combination with chemotherapy, for ovarian cancer. Understanding the tumor molecular biology and identification of predictive biomarkers are essential steps for selection of the best treatment strategies. This article reviews the molecular mechanisms of the most promising targeted agents that are under early phase clinical evaluation for ovarian cancer.

Progress in the diagnosis and treatment of extensive-stage small cell lung cancer

Lung cancer, being the most common cancer type, accounts for 13% of all newly diagnosed malignant tumors globally each year. Small cell lung cancer(SCLC) accounts for approximately 15% of newly diagnosed lung cancers each year, but its annual death toll accounts for 25% of that of lung cancer. We summarized relevant clinical studies to elaborate the epidemiology, pathological and clinical characteristics and the treatment status of small cell lung cancer. This paper first described the epidemiology and the pathological and clinical characteristics of SCLC and the systematic treatment of extensive-stage SCLC and then introduced the current targeted therapy and immunotherapy for SCLC to provide clinicians and patients with a more systematic, comprehensive, and beneficial treatment regimen. We expect that these studies can provide clinicians with a clear direction in molecularly targeted therapy or immunotherapy, so that a treatment approach with better antitumor effects and longer-lasting clinical benefits can be provided to the patients.

Therapeutic management options for stage Ⅲ non-small cell lung cancer

Lung cancer is the leading cause of cancer death worldwide.Majority of newly diagnosed lung cancers are non-small cell lung cancer(NSCLC), of which up to half are considered locally advanced at the time of diagnosis.Patients with locally advanced stage Ⅲ NSCLC consists of a heterogeneous population, making management for these patients complex.Surgery has long been the preferred local treatment for patients with resectable disease.For select patients, multimodality therapy involving systemic and radiation therapies in addition to surgery improves treatment outcomes compared to surgery alone.For patients with unresectable disease, concurrent chemoradiation is the preferred treatment.More recently, research into different chemotherapy agents, targeted therapies, radiation fractionation schedules, intensity-modulated radiotherapy, and proton therapy have shown promise to improve treatment outcomes and quality of life.The array of treatment approaches for locally advanced NSCLC is large and constantly evolving.An updated review of past and current literature for the roles of surgery, chemotherapeutic agents, radiation therapy, and targeted therapy for stage Ⅲ NSCLC patients are presented.

New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers

Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy,including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemoresistance and serious adverse effects. Advances in our understanding of changes affecting the interactome in advanced and chemoresistant breast tumors have provided novel therapeutic targets, including, cyclin dependent kinases, mammalian target of rapamycin,Notch, Wnt and Shh. Inhibitors of these molecules recently entered clinical trials in mono- and combination therapy in metastatic and chemo-resistant breast cancers. Anticancer epigenetic drugs, mainly histone deacetylase inhibitors and DNA methyltransferase inhibitors, also entered clinical trials. Because of the complexity and heterogeneity of breast cancer, the future in therapy lies in the application of individualized tailored regimens. Emerging therapeutic targets and the implications for personalized-based therapy development in breast cancer are herein discussed.

EGFR inhibitors sensitize non-small cell lung cancer cells to TRAIL-induced apoptosis

Apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) can be regulated by the epidermal growth factor(EGF) signaling pathway.In this study,recombinant adenoviral vectors that encode TRAIL gene from the hTERT/RGD promoter(AdTRAIL) was combined with drugs including gefitinib,elotinib,and cetuximab that inhibit EGFR and the EGF signaling pathway in non-small cell lung cancer(NSCLC) cell lines to investigate their antitumor activity.In vitro,compared to single reagent,AdTRAIL combined with EGFR inhibitors reduced proliferation and enhanced apoptosis in H460,A549,and SW1573 cell lines.Western blot results suggested that these effects were relative to up-regulation of pro-apoptosis protein BAX and down-regulation of p-AKT.In vivo,AdTRAIL combined with cetuximab resulted in a significant growth reduction in H460 xenografts without damage to the main organs of nude mice.Histological examination and TUNEL analyses of xenografts showed that cetuximab enhanced cell apoptosis induced by AdTRAIL.These results indicate that EGFR inhibitors enhanced AdTRAIL anti-tumor activity in NSCLC cell lines and that inhibiting the AKT pathway played an important role in this enhancement.

Molecularly targeted therapies for advanced or metastatic non-small-cell lung carcinoma

Non-small-cell lung cancer(NSCLC)remains the leading cause of cancer-related death in both men and women in the United States.Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease.Improvements in overall survival and quality of life have been modest.Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics,thus changing the treatment paradigm for many NSCLC patients.In this review,we present a summary of many of the currently investigated biologic targets in NSCLC,discuss their current clinical trial status,and also discuss the potential for development of other targeted agents.

Targeted therapies for patients with advanced NSCLC harboring wild-type EGFR:what's new and what's enough

Historically,non-small cell lung cancer(NSCLC) is divided into squamous and nonsquamous subtypes based on histologic features.With a growing number of oncogenic drivers being identified in squamous and nonsquamous NSCLC,this malignancy has been recently divided into several distinct subtypes according to the specific molecular alterations.This new paradigm has substantially highlighted the treatment of advanced NSCLC,shifting it from standard chemotherapy according to specific histologic subtypes to targeted therapy according to specific oncogenic drivers.The application of epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs) in NSCLC patients harboring activating EGFR mutations has been a representative model of precise medicine in the treatment of NSCLC.As the role of EGFR-TKIs in routine management of patients with advanced NSCLC has been well established,this review provides an overview of alternative targeted therapy in the treatment of NSCLC,including EGFR-TKIs for patients with wild-type EGFR NSCLC,as well as other targeted agents either clinical available or in early- to late-stage development.

Monoclonal Antibodies: An Emerging Class of Therapeutics in Non Small Cell Lung Cancer

Lung cancer is the leading cause of cancer-related deaths in industrialized countries and non small cell lung cancer (NSCLC) accounts for 85% of all lung cancers. Cisplatin doublet based chemotherapy, which is the recommended regimen in first line therapy in advanced or metastatic NSCLC, improves survival but in low proportion. Monoclonal antibodies (mAbs) are a novel promising therapeutic class used with great results in inflammatory diseases such as rheumatoid arthritis. Antibodies are natural proteins with modular structure, specific pharmacodynamics and pharmacokinetics and possibly produced against any antigens, thus giving them several advantages over small drug therapeutics. In solid tumors, therapeutic mAbs improved progression free survival (PFS) and overall survival (OS) of patients with breast and colon cancers and had considerably changed the treatment in clinical practice. In NSCLC, bevacizumab, an anti-VEGF mAb, and cetuximab, an anti-EGFR mAb, are the most studied antibodies. Bevacizumab acts on angiognenesis and improved PFS of non squamous NSCLC but in low proportion as shown in two large phase III trials. It was approved by European Medicines Agency (EMEA) and Food and Drug administration (FDA) as a first line therapy in combination with cisplatin doublet chemotherapy. Cetuximab slightly enhanced OS but did not improve PFS in two large phase III trials. These results added to high adverse effect lead to cetuximab refusal by EMEA and FDA in NSCLC. At first glance, the results of mAbs in NSCLC are somewhat disappointing, in contrast to the benefits obtained with mAb treatments in other solid tumors. However, many other mAbs directed against novel targets, such as IGF1-R or CTLA-4, and new mAbs targeting VEGFR and EGFR pathways with different pharmacodymamical and pharmacokinetic properties are under evaluation and may change our vision of taking care of patients with NSCLC. In conclusion, it seems that mAbs therapy in NSCLC clearly marks the start of a new era in NSCLC treatment, with promises in improving patient survival and quality of life.

2023年度非小细胞肺癌外科治疗进展

肺癌是当前世界各地最普遍和最致命的癌症,严重威胁人们的生命健康。外科手术切除是最早治疗肺癌的手段,也是目前肺癌最主要的治疗手段。随着医学技术的进步,外科手术方法和辅助治疗策略不断革新,这为肺癌患者带来了新的希望。因此总结肺癌外科治疗领域的最新研究进展具有重要意义。本文旨在综述2023年度非小细胞肺癌(non-small cell lung cancer,NSCLC)外科治疗的主要进展,包括手术技术的创新、微创手术、辅助分子靶向治疗及免疫治疗在NSCLC围手术期的应用等。

系统性硬皮病靶向治疗研究进展

系统性硬皮病(SSc)作为一种免疫介导的慢性结缔组织疾病,以皮肤、肺等多器官纤维化为主要临床表现,属于罕见病范畴,但发病率和死亡率在风湿免疫性疾病中均排在前列。目前尚无有效的治疗药物。近年来研究发现,T/B淋巴细胞、成纤维细胞、内皮细胞等相互作用及各种促炎促纤维化信号分子激活在其发生发展中起着关键性作用,在此基础上正在研发系列靶向药物。其中靶向B细胞耗竭的CD20单克隆抗体(利妥昔单抗)、IL-6受体拮抗剂(托珠单抗)、多靶点酪氨酸激酶抑制剂(尼达尼布)等在国际上已被批准用于SSc或系统性硬化病相关间质肺疾病(SSc-ILD)治疗;其他靶向药物如Janus激酶抑制剂、多种白介素抑制剂等在临床试验阶段,部分展现初步应用前景。本文从靶向B淋巴细胞、T淋巴细胞、血管内皮细胞及促炎促纤维化信号分子4个方面综合最新证据,就靶向疗法在SSc中的研究进展进行综述。

放射治疗联合靶向疗法对非小细胞肺癌晚期患者临床有效性研究

目的 研究放射治疗联合靶向疗法对非小细胞肺癌(Non-Small Cell Lung Cancer, NSCLC)晚期患者的临床有效性。方法 方便选取2022年6月—2023年6月山东省淄博市中心医院收治的96例非小细胞肺癌晚期患者为研究对象,采用随机数表法分为对照组和观察组,每组48例。对照组采用放射治疗,观察组采用放射治疗联合靶向疗法。比较两组疗效、肿瘤标志物、免疫功能、不良反应发生率。结果 观察组缓解率(56.25%)和疾病控制率(87.50%)高于对照组(35.42%、68.75%),差异有统计学意义(χ^(2)=4.196、4.937,P均<0.05)。治疗后,观察组细胞角蛋白19片段、癌胚抗原、糖类抗原199、CD8^(+)水平均低于对照组,CD4^(+)、CD3^(+)水平高于对照组,差异有统计学意义(P均<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论 放射治疗联合靶向疗法对非小细胞肺癌晚期患者治疗效果高,可获得更高的控制率,能有效下调细胞角蛋白19片段、癌胚抗原、糖类抗原199水平,调节免疫,且不增加不良反应。

奥希替尼靶向治疗晚期非小细胞肺癌临床研究

目的探讨奥希替尼靶向治疗晚期非小细胞肺癌(NSCLC)的临床疗效。方法选取医院肿瘤科2021年1月至2022年12月收治的晚期NSCLC患者113例,根据治疗方案的不同分为化学药物治疗(简称化疗)组(54例)和靶向治疗(简称靶向)组(59例)。化疗组患者予注射用培美曲塞二钠+注射用顺铂静脉滴注,靶向组患者口服甲磺酸奥希替尼片。结果靶向组疾病控制率为93.22%,显著高于化疗组的74.07%(P<0.05)。两组患者治疗后的血清癌胚抗原、鳞状上皮细胞癌抗原、细胞角蛋白19片段抗原21-1水平均显著降低(P<0.05),且靶向组患者改善幅度显著大于化疗组(P<0.05)。靶向组患者治疗后的T淋巴细胞亚群CD_(4)^(+)水平显著升高,CD_(8)^(+)水平显著降低,CD_(4)^(+)/CD_(8)^(+)显著升高(P<0.05)。靶向组不良反应发生率为11.86%,显著低于化疗组的29.63%(P<0.05)。结论奥希替尼靶向治疗晚期NSCLC,可降低患者的血清肿瘤细胞因子水平,且对免疫功能影响轻微。