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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.
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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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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4.
Hydrogen bond analysis of the EGFR-ErbB3 heterodimer related to non-small cell lung cancer and drug resistance.
Ghosh, A, Yan, H
Journal of theoretical biology. 2019;:63-71
Abstract
Lung cancer is the predominant cause of cancer deaths on a worldwide scale. A mutation in the epidermal growth factor receptor (EGFR) can cause non-small cell lung cancer (NSCLC). The L858R one-point mutation in exon 21 in EGFR is the most prevalent in NSCLC. For over 60% of EGFR-muted NSCLC, another mutation T790M can cause drug resistance. In this paper, we consider EGFR and ErbB3 heterodimers involving three structures of EGFR, wild-type, with L858R mutation, and with L858R and T790M mutations. We perform molecular dynamics (MD) simulations to analyze hydrogen bonds in all three instances. The hydrogen bonds contribute to the conformational stability of the protein and molecular recognition. Several other parameters are also investigated in the present study, which reveals significant changes in the dimer at different levels of mutation. The knowledge and results obtained from this study lead to useful insight into the mechanism of NSCLC drug resistance.
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5.
Acquired haemophilia A in a patient with breast cancer and lung carcinoma: a case report and literature review.
Biesheuvel, V, Hiddema, SM, Levenga, H, Eikenboom, J, van der Deure, WM
The Netherlands journal of medicine. 2019;(4):153-155
Abstract
Acquired haemophilia A is a rare disorder caused by spontaneous formation of auto-antibodies (inhibitors) against coagulation factor VIII. This can lead tolife-threatening haemorrhages. Six to twenty-two percent of patients with acquired haemophilia have an underlying malignancy. We describe a 69-year-old woman with metastatic breast cancer and non-small cell lung carcinoma who presented at the emergency room with spontaneous bruising, and who was using a vitamin K antagonist. She had a prolonged activated partial thromboplastin time (aPTT) due to a coagulation factor VIII deficiency caused by factor VIII antibodies. She was treated with prednisone and cyclophosphamide.
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6.
Brigatinib: Novel ALK Inhibitor for Non-Small-Cell Lung Cancer.
Spencer, SA, Riley, AC, Matthew, A, Di Pasqua, AJ
The Annals of pharmacotherapy. 2019;(6):621-626
Abstract
OBJECTIVE We review here the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions and place in therapy of brigatinib for abnormal anaplastic lymphoma kinase (ALK) specific non-small-cell lung cancer (NSCLC). DATA SOURCES A literature search using PubMed was conducted using the terms brigatinib and ALK positive NSCLC from January 2013 to November 2018. STUDY SELECTION AND DATA EXTRACTION All English-language articles evaluating brigatinib were analyzed for this review. DATA SYNTHESIS Brigatinib was granted approval for the treatment of patients with metastatic ALK+ NSCLC who have progressed on or are intolerant to crizotinib. It is administered at a dose of 90 mg orally once daily for the first 7 days then, if tolerated, increased to a dose of 180 mg orally once daily. Common adverse effects include nausea, fatigue, diarrhea, increased creatine phosphokinase levels, headache, dyspnea, and hypertension. Serious treatment-emergent adverse effects were pulmonary related. Relevance to Patient Care and Clinical Practice: This article discusses the clinical trials that led to the accelerated approval of brigatinib for its ability to overcome crizotinib-resistant mutations and for its increased central nervous system penetration properties. CONCLUSION Brigatinib was granted accelerated approval for the treatment of patients with metastatic ALK+ NSCLC who have progressed on or are intolerant to crizotinib. In a subset of NSCLC patients, brigatinib increases survival for approximately 1 year; however, side effects were detected.
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7.
Pretreatment prognostic nutritional index as a prognostic factor in lung cancer: Review and meta-analysis.
Wang, Z, Wang, Y, Zhang, X, Zhang, T
Clinica chimica acta; international journal of clinical chemistry. 2018;:303-310
Abstract
BACKGROUND Numerous studies have explored the association between pretreatment prognostic nutritional index (PNI) and prognosis in lung cancer (LC), but the results are still inconclusive. We systematically evaluated the prognostic value of pretreatment PNI in LC patients by conducting a meta-analysis. METHODS A comprehensive literature search was performed by retrieving PubMed, EMBASE, and Web of Science, Wan Fang and CNKI databases. We used hazard ratios (HRs) and their 95% confidence intervals (CIs) to assess the associations of PNI with overall survival (OS), disease-free survival/recurrence-free survival (DFS/RFS) and progression-free survival (PFS) in LC patients. RESULTS A total of 21 studies were enrolled into this meta-analysis, with 17 about no-small cell lung cancer (NSCLC) and 4 about on small-cell lung cancer (SCLC). The results indicated that NSCLC patients with low PNI had shorter OS (HR: 1.59, 95% CI: 1.28-1.96, P = 0.001), DFS/RFS (HR = 1.74, 95% CI = 1.08-2.80, P = 0.017), and PFS (HR = 1.52, 95% CI = 1.26-1.83, P = 0.002) than patients with high PNI. The robustness of these pooled results were verified by our stratified analysis and sensitivity analysis. Besides, a pooled analysis of 4 studies about SCLC suggested that low PNI was closely associated with worse OS in SCLC patients as well. CONCLUSION Low PNI predicts poor survival in LC patients.
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8.
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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9.
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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Association between Retinoic acid receptor-β hypermethylation and NSCLC risk: a meta-analysis and literature review.
Li, Y, Lu, DG, Ma, YM, Liu, H
Oncotarget. 2017;(4):5814-5822
Abstract
Emerging evidence indicates that Retinoic acid receptor-β (RARβ) is a tumor suppressor in many types of tumor. However, whether or not RARβ is a risk factor and is correlated to clinicopathological characteristics of non-small cell lung cancer (NSCLC) remains unclear. In this report, we performed a meta-analysis to determine the effects of RARβ hypermethylation on the incidence of NSCLC and clinicopathological characteristics in human NSCLC patients. Final valuation and analysis of 1780 cancer patients from 16 eligible studies was performed. RARβ hypermethylation was found to be significantly higher in NSCLC than in normal lung tissue, the pooled OR from 7 studies including 646 NSCLC and 580 normal lung tissues, OR = 6.05, 95% CI = 3.56-10.25, p<0.00001. RARβ hypermethylation was significantly higher in adenocarcinoma (AC) compared to squamous cell carcinoma (SCC), pooled OR is 0.68 (95% CI = 0.52-0.89, p = 0.005). RARβ hypermethylation was also found to occur significantly higher in smoker (n = 232) than non-smoker (n = 213) (OR = 2.46, 95% CI = 1.54-3.93, p = 0.0002). Our results indicate that RARβ hypermethylation correlates well with an increased risk in NSCLC patients. RARβ geneinactivation caused by RARβ methylation contributes the NSCLC tumorigenesis and may serve as a potential risk factor, diagnostic marker and drug target of NSCLC.