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1.
Early-onset meningitis associated with atezolizumab treatment for non-small cell lung cancer: case report and literature review.
Ogawa, K, Kaneda, H, Kawamoto, T, Tani, Y, Izumi, M, Matsumoto, Y, Sawa, K, Suzumura, T, Watanabe, T, Mitsuoka, S, et al
Investigational new drugs. 2020;(6):1901-1905
Abstract
Immune checkpoint inhibitors (ICIs) have improved the overall survival of many patients with advanced cancers. However, unlike cytotoxic and targeted drugs, ICIs may cause various immune-related adverse events (irAEs). Among these irAEs, autoimmune meningitis is very rare. Here, we report a case of early-onset, atezolizumab-induced meningitis after administration of one dose of atezolizumab. A 56-year-old man with lung adenocarcinoma had received seventh-line treatment with atezolizumab when he experienced dysarthria. Blood examinations, including the measurement of electrolytes, glucose, and organ functions, were unremarkable, but enhanced head magnetic resonance imaging T1-weighted images showed meningeal enhancement. Although cerebral spinal fluid (CSF) examinations revealed elevated lymphocyte and protein levels, no cancer cells were detected in the CSF. CSF cultures and serological tests, including polymerase chain reaction for herpes simplex virus, were negative. The patient was therefore diagnosed with atezolizumab-triggered autoimmune meningitis. With steroid treatment, the patient's clinical and neurological state improved immediately and he recovered to baseline conditions. Prompt diagnosis and therapeutic intervention are essential for the effective treatment of autoimmune meningitis.
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2.
The evolving role of pemetrexed disodium for the treatment of non-small cell lung cancer.
Rossi, G, Alama, A, Genova, C, Rijavec, E, Tagliamento, M, Biello, F, Coco, S, Dal Bello, MG, Boccardo, S, Grossi, F
Expert opinion on pharmacotherapy. 2018;(17):1969-1976
Abstract
Non-small cell lung cancer (NSCLC) remains one of the big cancer killers, despite the introduction of a number of approved therapeutics in recent times. Pemetrexed is a multi-target folate inhibitor, which is currently available to patients affected by advanced non-squamous NSCLC in combination with a platinum derivate in first-line therapy and as a single agent in second-line therapy. Areas covered: This review covers presents the use pemetrexed in the management of NSCLC by exploring the data available from clinical trials and meta-analyses. Data from a phase III trial confirmed its role in the first-line setting in combination with immune checkpoint inhibitors (ICIs). Furthermore, data suggested a role for pemetrexed in local and advanced NSCLC. Expert opinion: To date, in spite of the introduction of novel anti-neoplastic agents, pemetrexed still represents a cornerstone in the management of non-squamous NSCLC. Furthermore, recently published data support its role in innovative combinations including together with chemotherapy and immunotherapy.
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3.
The Mevalonate Pathway and Innate Immune Hyper-Responsiveness in the Pathogenesis of COPD and Lung Cancer: Potential for Chemoprevention.
Young, RP, Hopkins, RJ
Current molecular pharmacology. 2017;(1):46-59
Abstract
Current evidence suggests that persisting and/or exaggerated inflammation in the lungs initiated by smoking, and up-regulated through genetic susceptibility, may result in lung remodelling and impaired repair. The mevalonate pathway, through its modifying effects on innate immune responsiveness, may be involved in these processes providing a plausible pathogenic link between the development of chronic obstructive pulmonary disease (COPD) and lung cancer. The mevalonate pathway, mediates these effects through important intra-cellular signalling molecules called guanine phosphate transferases (GTPases) such as Rho-A. Smoke exposure activates cell surface proteins which, through the mediating influence of GTPases, then modify the activation of NFkB and its downstream effects on genes underlying innate immunity, neutrophilic inflammation and carcinogenesis. The mevalonate pathway is readily and substantially modified by inhibition of the enzyme 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMGCo-A) reductase. This enzyme controls the rate limiting step of the mevalonate pathway and is subject to inhibition by statin drugs and small chain fatty acids derived from high dietary fibre intake. Thus inhibiting the mevelonate pathway, and dampening the innate immune response to smoking, may play a critical role in modifying pulmonary inflammation and lung remodelling. Such an action might slow the progression of COPD and reduce the tendency to the development of lung cancer. This review examines the pre-clinical and clinical data suggesting that HMGCoA-reductase inhibition and it's modification of the mevalonate pathway, may have a chemo-preventive effect on lung cancer, particularly in patients with COPD where pulmonary inflammation is increased and the risk of lung cancer is greatest.
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4.
Coexisting myasthenia gravis, myositis, and polyneuropathy induced by ipilimumab and nivolumab in a patient with non-small-cell lung cancer: A case report and literature review.
Chen, JH, Lee, KY, Hu, CJ, Chung, CC
Medicine. 2017;(50):e9262
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Abstract
RATIONALE Immune checkpoint inhibitors have led to the development of new approaches for cancer treatment with positive outcomes. However, checkpoint blockade is associated with a unique spectrum of immune-related adverse events (irAEs), which may cause irreversible neurological deficits and even death. PATIENT CONCERNS We presented a case of a 57-year-old man with non-small-cell lung cancer.who developed ptosis, dyspnea, and muscle weakness as initial symptoms with progression after the treatment with ipilimumab and nivolumab. DIAGNOSES Myasthenia gravis was confirmed by serum acetylcholine receptor antibody and single fiber electromyography. Myositis was identified by high level of serum creatine phosphokinase and electromyography. Polyneuropathy was identified by nerve conduction study. INTERVENTIONS The patient underwent treatment with steroid and pyridostigmine. Respiratory rehabilitation was also performed. OUTCOMES Dyspnea and muscle weakness improved gradually. Ipilimumab and nivolumab were permanently discontinued. LESSONS This case has increased the clinical awareness by indicating that the checkpoint inhibitors-related neurological irAEs could be complicated and simultaneously involve multiple neurological systems. Early recognition and complete evaluation are critical in clinical practice.
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Metronomic oral vinorelbine in advanced breast cancer and non-small-cell lung cancer: current status and future development.
Cazzaniga, ME, Camerini, A, Addeo, R, Nolè, F, Munzone, E, Collovà , E, Del Conte, A, Mencoboni, M, Papaldo, P, Pasini, F, et al
Future oncology (London, England). 2016;(3):373-87
Abstract
Metronomic chemotherapy (mCT), a frequent administration of low-dose chemotherapy, allows prolonged treatment duration and minimizes the toxicity of standard-dose chemotherapy. mCT has multiple actions against cancer cells including inhibition of angiogenesis and modulation of the immune system. A number of studies lend support to the clinical efficacy of mCT in advanced breast cancer and non-small-cell lung cancer. However, further evidence is necessary to describe the optimal use of mCT and to identify suitable patients. Oral vinorelbine has emerged as a promising metronomic treatment in patients with metastatic breast cancer and non-small-cell lung cancer and is the only orally available microtubule-targeting agent. This paper reviews current evidence on metronomic oral vinorelbine, discusses its management and defines a suitable patient profile on the basis of a workshop of Italian experts.
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Chemotherapy for Advanced Non-small Cell Lung Cancer.
Dietrich, MF, Gerber, DE
Cancer treatment and research. 2016;:119-49
Abstract
Non-small cell lung cancer has seen an unprecedented augmentation of therapeutic options over the last couple of years. Improved understanding of molecular drivers and the role of the immune system in cancer therapy have brought new drugs to the armamentarium. Despite these advances, cytotoxic chemotherapy remains a substantial part of therapy for most patients in locally advanced and metastatic stage. Initially thought to be a chemotherapy-resistant entity, meta-analyses in the mid-1990s demonstrated modest efficacy of platinum-based therapy. Further combination trials demonstrated enhanced efficacy for several regimen in first and second lines, including the introduction of antimetabolites, taxanes, and anti-angiogenic agents. Maintenance chemotherapy has been another novel, successful approach for management of metastatic disease. Herein, we summarize the current concepts of chemotherapy, its applicability to the different histologies, and novel concepts of therapy.
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[Research progress of nutrition support for patients with lung cancer during chemotherapy].
Luo, Y, Zhu, J
Zhongguo fei ai za zhi = Chinese journal of lung cancer. 2014;(12):865-9
Abstract
Primary lung cancer is one of the most common malignancies. Nowadays, both its morbidity and mortality rank first, patients with lung cancer are often goes with some affiliating symptoms such as malnutrition and weight loss. The side effects of cytotoxicity during chemotherapy may lead to further deteriorate of the nutritional status and worsen the anti-tumor therapy's efficacy and the patients' quality of life. With the development of palliative treatment and the higher request of patients for quality of life, nutritional support will be an important adjunctive treatment to maintain a good nutritional status and enhance the patients' immunity during chemotherapy. It will play an active role in improving tolerability of chemotherapy and prognosis for patients with lung cancer. Here is a review about research progress of nutrition support treatment during chemotherapy for the patients with lung cancer.
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The importance of matrix metalloproteinase-3 in respiratory disorders.
Yamashita, CM, Radisky, DC, Aschner, Y, Downey, GP
Expert review of respiratory medicine. 2014;(4):411-21
Abstract
The matrix metalloproteinases (MMPs) encompass a family of zinc-dependent endopeptidases that are secreted into the extracellular environment or remain bound to the cell surface. While MMPs were initially identified based on their ability to degrade collagen and other components of the extracellular matrix, recent studies indicate that their non-degradative functions are physiologically paramount. In particular, MMPs are now known to participate in diverse physiological processes that control key aspects of inflammatory and immune responses and neoplasia, in part by selective triggering of cellular signaling pathways via limited proteolytic processing of extracellular and membrane-associated proteins, including cytokines and cell surface receptors. Herein, we focus on the unique roles of MMP-3 (stromelysin-1) in acute lung injury and repair, pulmonary fibrosis, and lung cancer.
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Effect of injection of brucea javanica oil emulsion plus chemoradiotherapy for lung cancer: a review of clinical evidence.
Nie, YL, Liu, KX, Mao, XY, Li, YL, Li, J, Zhang, MM
Journal of evidence-based medicine. 2012;(4):216-25
Abstract
OBJECTIVE Injection of brucea javanica oil emulsion (IBJOE), one of Chinese patent drugs has been widely used for lung cancer (LC) in China, and is known to provide some favorable outcomes, in particular when it combined with conventional treatment. However, little available best evidence is known about its effect and safety. This paper aims to evaluate the effectiveness and safety of IBJOE plus chemoradiotherapy to alleviate symptoms of LC patients. METHODS A complete literature searching was conducted in databases including Chinese Biomedical Literature Database, China Academic Journals Full-text Database, Chinese Scientific Journals Database, the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE to identify randomized controlled trials (RCTs) of IBJOE with chemoradiotherapy versus chemoradiotherapy alone for LC patients regardless of blinding, duration of treatment or duration of follow-up. All searching dates were from the beginning to December 2011. Quality of the included studies was assessed using the method by Cochrane Reviewer Handbook, and data analysis was performed using RevMan 5.10 software developed by The Cochrane Collaboration. RESULTS The searching yielded over 1371 relevant citations, most of which did not meet the inclusion criteria. Finally, only 21 RCTs involving 1619 patients were included, and all the studies were of poor quality. Pooled analyses were performed to reveal that compared with chemoradiotherapy alone, IBJOE plus chemoradiotherapy had a better complete response rate (relative risk (RR) = 1.42; 95% CI 1.05 to 1.92; P = 0.02) and improved quality of life (RR = 1.83; 95% CI 1.63 to 2.07; P < 0.00001) measured by Karnofsky Performance Status scale. In addition, there was a significant difference on the outcome of long-term survival rate, level of immune function, and some incidences of adverse effects. CONCLUSIONS IBJOE plus chemoradiotherapy may have positive effects on LC patients in response rate, improvement of quality of life, and reducing incidences of some adverse effects compared with chemoradiotherapy alone. However, the results need to be viewed with caution because of low quality of the included studies.
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10.
[Aidi Injection as an adjunct therapy for non-small cell lung cancer: a systematic review].
Ma, WH, Duan, KN, Feng, M, She, B, Chen, Y, Zhang, RM
Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine. 2009;(4):315-24
Abstract
OBJECTIVE To assess methodological quality of clinical studies using Aidi Injection as an adjunct therapy for non-small cell lung cancer (NSCLC) and to evaluate the effects of Aidi Injection. METHODS PubMed (1980-2008), Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2008), EMBASE (1984-2008), CancerLit (1996-2003), CBMdisc (1980-2008), CNKI database (1980-2008), Wanfang database (1980-2008), and Chongqing VIP database (1980-2008) were searched. The authors also hand-searched Chinese periodicals potentially related to the question. All randomized controlled trials comparing Aidi Injection with other treatment methods of NSCLC were included. Two reviewers selected studies, assessed the quality of studies, and extracted the data independently. The included studies were appraised and analyzed by Cochrane Collaboration Review Manager 5.0. RESULTS Fourteen randomized controlled trials were included in the meta-analysis, but the quality of reports of the 14 included studies was poor. Aidi Injection combined with cobalt-60 or navelbine and platinol (NP) showed statistically significant differences in improving the response rate as compared with single use of cobalt-60 (P=0.000 2) or NP (P=0.04), and the relative risk (RR) and 95% confidence interval (CI) were 1.93 [1.36, 2.72] and 1.18 [1.00, 1.38], respectively. However, Aidi Injection combined with etoposide and platinol (EP), taxinol and platinol (TP) or gamma knife showed no significant differences as compared with single use of EP (P=0.60), TP (P=0.16) or gamma knife (P=0.34), respectively. The RR and 95% CI of EP, TP and gamma knife were 1.17 [0.65, 2.09], 1.27 [0.91, 1.78] and 1.08 [0.92, 1.26] respectively. Six studies indicated that Aidi Injection combined with NP or gamma knife could improve the quality of life.Six studies showed that Aidi Injection combined with NP or TP could improve the bone marrow hematopoietic function.Three studies indicated that Aidi Injection combined with NP could improve the immune function. Three studies showed that the combined therapy could not improve 1-, 2-, and 3-year survival rates. CONCLUSION The results of meta-analysis indicate that Aidi Injection may have adjuvant therapeutic effects in treatment of NSCLC patients, but the sample size is too small and with poor quality, and the existence of publication bias is found.The effects of Aidi Injection need to be confirmed by large multicenter randomized controlled trials.