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1.
Pemetrexed - First-Line Therapy for Non-Squamous Non-Small Cell Lung Cancer: A Review of Patent Literature.
Vora, PA, Patel, R, Dharamsi, A
Recent patents on anti-cancer drug discovery. 2021;(3):333-349
Abstract
BACKGROUND Pemetrexed is a folate analogue metabolic inhibitor for mammalian cells. Pemetrexed is toxic to several cancer cells by interfering with their new biosynthesis of nucleotides, thus causing cell apoptosis. Presently, Pemetrexed is given to patients with Non-Small Cell Lung Cancer (NSCLC). OBJECTIVE This review focuses on the recent patents of Pemetrexed. This assessment includes patents grouped in segments like crystalline form patent, composition related patents, product patents, as well as a method of treatment. The aim of this review is to simplify inventors with existing patents in a single place. METHODS Data were searched from several available databases, including paid databases which include Orbit® and SciFinder®. Free databases include Worldwide Espacenet® (EPO), Patentscope® (WIPO), InPASS (Indian patent database) and Google Patents. RESULTS Some new polymorph and composition-related inventions of Pemetrexed have been recently patented as its orange-book listed patents will soon expire in May 2022. Further, because of the problem of oxidation through the development and continuing storage of Pemetrexed composition, several excipients are experimented with within these patents to stabilize the same. Nevertheless, there is a need for further development of an improved composition of Pemetrexed with improved characteristics. CONCLUSION Wide research has been conducted on different processes for preparing Pemetrexed and formulation thereof. Such type of active research may clear the track for the generic companies in the United States, producing the formulation at low prices and providing universal health care at economical prices.
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2.
Metronomic therapy in advanced breast cancer and NSCLC: vinorelbine as a paradigm of recent progress.
Xu, B, Sun, T, Wang, S, Lin, Y
Expert review of anticancer therapy. 2021;(1):71-79
Abstract
INTRODUCTION Metronomic chemotherapy (MCT) is based on frequent dosing of the drug. . This leads to pharmacologically active but low plasma concentrations that reduce toxicity. MCT seems to work primarily via indirect effects on tumor cells and their microenvironment, rather than direct antitumor effects. Oral vinorelbine is one of the most widely studied MCT approaches in both advanced breast cancer and non-small cell lung cancer. EXPERT OPINION MCT with vinorelbine has proven efficacy, tolerability and quality of life benefits both as monotherapy and in combination with other MCTs or targeted agents, in first-line therapy and in previously treated patients. Key populations are emerging who may be particularly well suited to metronomic vinorelbine, including those with indolent disease, older individuals, and those with multiple comorbidities and/or bone metastases. Ongoing trials should help to further delineate these target groups. Additional work is needed to better understand the optimal vinorelbine regimen, particularly when used in combination or in non-Caucasian patients. Markers are also required to help identify individuals who are most likely to respond. Nonetheless, the efficacy and tolerability of MCT, allied to improved patient convenience, reduced need for medical engagement and lower cost, make it an appealing option - particular in resource-constrained healthcare environments.
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3.
Nutritional Support in Lung Cancer Patients: The State of the Art.
Mele, MC, Rinninella, E, Cintoni, M, Pulcini, G, Di Donato, A, Grassi, F, Trestini, I, Pozzo, C, Tortora, G, Gasbarrini, A, et al
Clinical lung cancer. 2021;(4):e584-e594
Abstract
Lung cancer (LC) represents the most commonly diagnosed neoplasm worldwide for both sexes and is the leading cause of cancer mortality. Malnutrition is a comorbidity frequently found in neoplastic patients, but it remains often underestimated and thus undertreated. In this review, we aimed to investigate the incidence of malnutrition among LC patients according to different screening and assessment tools, to evaluate the impact of weight loss and body composition on survival, and to analyze the efficacy of different nutritional interventions in this setting. Although malnutrition, weight loss, and body composition changes can affect survival and other clinical outcomes in LC patients, the role of nutritional interventions is not yet strongly proven, and further studies are recommended. Nevertheless, screening, assessing, and eventually treating malnutrition in LC patients are strongly recommended, according to the most recent nutritional intervention guidelines for oncology patients.
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4.
Sintilimab induced diabetic ketoacidosis in a patient with small cell lung cancer: A case report and literature review.
Huang, X, Yang, M, Wang, L, Li, L, Zhong, X
Medicine. 2021;(19):e25795
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Abstract
RATIONALE Sintilimab is a novel programmed cell death receptor-1 (PD-1) inhibitor approved in the treatment of classical Hodgkin's lymphoma and undergoing clinical trials for various malignancies. As a PD-1 inhibitor, sintilimab is known to cause autoimmune adverse events similar to other PD-1 inhibitors. Diabetic ketoacidosis (DKA) is a rare but severe adverse event of this therapy. PATIENT CONCERNS We report a case of a 59-year-old man who developed DKA after 5 doses of sintilimab for small cell lung cancer. His fasting glycemia level was 14.07 mmol/L, urine ketone bodies were 4+, arterial blood pH was 7.271, bicarbonate was 12.3 mmol/L, and glycated hemoglobin (HbA1c) was 7.4%. Extended investigations revealed that fasting C-peptide was undetectable (<0.003 nmol/L). DIAGNOSIS These laboratory investigations supported the diagnosis of fulminant type 1 diabetes mellitus, but no β-cell related antibodies were positive. INTERVENTIONS After remission of DKA, he was treated with insulin therapy to acquire a normalization of glycemia and the disappearance of symptoms. OUTCOMES Sintilimab was withheld after 6 cycles and was converted to durvalumab to sustain the therapeutic effect. LESSONS This case and associated literature review illustrate the importance of educating and monitoring patients who start PD-1 inhibitor therapy regarding this potentially life-threatening complication.
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5.
Exercise prehabilitation in lung cancer: Getting stronger to recover faster.
Avancini, A, Cavallo, A, Trestini, I, Tregnago, D, Belluomini, L, Crisafulli, E, Micheletto, C, Milella, M, Pilotto, S, Lanza, M, et al
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2021;(8):1847-1855
Abstract
Despite several recent advances, lung cancer surgery is still associated with potentially severe postoperative complications. It has been suggested that preoperative exercise training could render patients with borderline functional parameters eligible for surgery, improve perioperative outcomes and that these benefits might reduce healthcare costs. Nevertheless, given the substantial heterogeneity of the available studies, no specific guidelines for preoperative exercise training have been released so far. This narrative review aims to provide an overview of the potential benefits of exercise training in the preoperative period as a central intervention for lung cancer patients. In detail, the effects of exercise (with different regimens) were evaluated in terms of physical functions, patients' eligibility for curative surgery, postoperative complications and length of stay, with an exploratory focus on healthcare costs and long-term outcomes. Furthermore, a feasible approach for every-day clinical practice is proposed in order to increase the expected benefit deriving from a more extensive and methodical application of prehabilitation exercise, ideally in the context of a comprehensive approach to lung cancer patients, including nutritional and psychological support.
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6.
Salivary Biomarkers in Lung Cancer.
Skallevold, HE, Vallenari, EM, Sapkota, D
Mediators of inflammation. 2021;:6019791
Abstract
A very low percentage of lung cancer (LC) cases are discovered at an early and treatable stage of the disease, leading to an abysmally low 5-year survival rate. This underscores the immediate necessity for improved diagnostic, prognostic, and predictive biomarkers for LC. Biopsied lung tissue, blood, and plasma are common sources used for LC diagnosis and monitoring of the disease. A growing number of studies have reported saliva to be a useful biological sample for early and noninvasive detection of oral and systemic diseases. Nevertheless, salivary biomarker discovery remains underresearched. Here, we have compiled the available literature to provide an overview of the current understanding of salivary markers for LC detection and provided perspectives for future clinical significance. Valuable markers with diagnostic and prognostic potentials in LC have been discovered in saliva, including metabolic (catalase activity, triene conjugates, and Schiff bases), inflammatory (interleukin 10, C-X-C motif chemokine ligand 10), proteomic (haptoglobin, zinc-α-2-glycoprotein, and calprotectin), genomic (epidermal growth factor receptor), and microbial candidates (Veillonella and Streptococcus). In combination, with each other and with other established screening methods, these salivary markers could be useful for improving early detection of the disease and ultimately improve the survival odds of LC patients. The existing literature suggests that saliva is a promising biological sample for identification and validation of biomarkers in LC, but how saliva can be utilized most effectively in a clinical setting for LC management is still under investigation.
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7.
Cancer genomics of lung cancer including malignant mesothelioma: A brief overview of current status and future prospects.
Jhanwar, SC, Xu, XL, Elahi, AH, Abramson, DH
Advances in biological regulation. 2020;:100723
Abstract
Cancer as a genetic disease is by now well recognized. Genomic analysis of cancer cells, therefore, has greatly enhanced our ability to identify genetic alterations associated with various cancer types, including both lympho-hematopoietic as well as solid tumors. Chronic myeloid leukemia (CML), based on the specific diagnostic genetic abnormality has served as a prototype disease to clearly demonstrate the significance of the genomic analysis of cancer in identifying targeted therapy. Such a success has provided extra ordinary opportunities to investigate the role of genetic abnormalities and the pathways amenable to targeted therapy, not only in blood cancers but solid tumors such as Lung, Brain, Colon, Renal, Breast cancers as well as other epithelial and mesenchymal tumors. The main focus of this presentation is to illustrate the role of genomic analysis in targeting lung cancer, based on abnormalities or the pathways deregulated in tumor cells from individual patients. Lung cancer is one of the most common epithelial cancers associated with chronic inflammation due to cigarette smoking and other environmental carcinogens, and includes four distinct histologic type; non-small cell lung cancer (NSCLC); small cell lung cancer (SCLC) and squamous cell lung cancer. According to current estimates, 1.3 million cases of lung cancer are expected to be diagnosed worldwide annually, resulting in one million deaths. Since the discovery that patient's tumors with specific mutations in the EGFR may be sensitive to targeted therapeutic approach and the subsequent realization that the such mutations in the gene are not as prevalent, several cancer centers including ours initiated intense efforts to find other mutations or genomic alterations, which may serve as targets of specific therapy. Such efforts have successfully resulted in a battery of genes such as KRAS, ALK, C-MET, HER-2/neu, ROS1, etc., which have helped oncologists to triage the patients for personalized therapies. A significant proportion of patients with lung cancer, however, do not show any of the above genetic abnormalities. Approximately 90% of lung cancers exhibit RB1 mutation/deletion and or KRAS mutations, therefore, the signaling pathways, which regulate multistep tumorigenesis in lung cancer, are important for the treatment of histologic subtypes of lung cancer, which includes NSCLC & SCLC. Equally important was the findings that similar signaling pathways are also shared by other solid tumor types. We have investigated the role of these pathways to target these cancers and develop new strategies to treat lung, brain and related cancers. In addition, our translational studies in other tumor types such as NF2 related malignancies, specifically, Malignant Mesothelioma (MM), in which NF2 related pathway amenable to targeted therapies was identified. Selected examples representing experimental approaches will be discussed to illustrate the critical role of translational research in developing novel therapeutics for the successful and durable responses in some of these cancer types.
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8.
Autophagy-related MicroRNAs in chronic lung diseases and lung cancer.
Rezaei, S, Mahjoubin-Tehran, M, Aghaee-Bakhtiari, SH, Jalili, A, Movahedpour, A, Khan, H, Moghoofei, M, Shojaei, Z, R Hamblin, M, Mirzaei, H
Critical reviews in oncology/hematology. 2020;:103063
Abstract
Chronic lung disease has become a leading cause of death in recent years. Despite several attempts to discover and develop new therapeutic approaches, patients often suffer a poor quality of life, and are faced with an increased risk of developing lung cancer. Lung cancer often occurs as an end-stage after years of chronic lung disease. An increased understanding of the pathophysiology of chronic lung disease may be obtained from studying the role of autophagy in its initiation and progression. MicroRNAs (miRNAs) play a critical role in the modulation of autophagy, and their deregulation could be associated with the initiation and progression of several chronic lung diseases. Herein, we documented that up/down regulation of miRNAs can activate or inhibit autophagy in chronic lung diseases including lung cancer. Therefore, theses miRNAs could be a promising therapeutic tool for lung cancer specially in drug-resistance lung cancer cells.
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9.
Are segmentectomy and lobectomy comparable in terms of curative intent for early stage non-small cell lung cancer?
Mimae, T, Okada, M
General thoracic and cardiovascular surgery. 2020;(7):703-706
Abstract
In 1995, Ginsberg et al. compared lobectomy with limited resection including segmentectomy and wide-wedge resection for stage I lung cancer in a randomized controlled trial and found that limited resection should not be applied to otherwise healthy patients with clinical stage IA lung cancer who can tolerate lobectomy. However, recent advances in diagnostic technology have improved the precision of detecting early-stage and small lung cancers. Therefore, whether radical segmentectomy, anatomical segmentectomy with hilar and mediastinal lymph node dissection (that is more valuable than wedge resection in terms of oncological aspects) and lobectomy are comparable in terms of curative intent for patients with early-stage non-small cell lung cancer (NSCLC) remains controversial. The role of segmentectomy differs according to tumor or patient characteristics. High resolution computed tomography findings of tumor size, location, and the presence or ratio of a ground glass opacity (GGO) component and the maximum of standardized uptake value on fluorine-18-2-deoxy-D-glucose positron emission tomography are important for selecting surgical procedures because the malignant potential of even early-stage NSCLC is variable. The ongoing JCOG0802/WJOG4607L, JCOG1211, and CALGB140503 trials will disclose the influence of segmentectomy for patients with early-staged NSCLCs that are small peripheral tumors based on preoperative high-resolution computed tomography findings about preserved pulmonary function and long-term prognosis. Segmentectomy is a key surgical procedure that general thoracic surgeons will need to master considering that it can be converted to lobectomy if the surgical margin is insufficient or lymph node metastasis is intraoperatively confirmed.
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10.
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.