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https://www.readbyqxmd.com/read/28814805/intercalating-and-maintenance-gefitinib-plus-chemotherapy-versus-chemotherapy-alone-in-selected-advanced-non-small-cell-lung-cancer-with-unknown-egfr-status
#1
Hong Jian, Wei Li, Zhiyong Ma, Jianjin Huang, Jifeng Feng, Yong Song, Beili Gao, Huili Zhu, Min Tao, Chong Bai, Shenglin Ma, Hongming Pan, Shukui Qin, Dong Hua, Yongfeng Yu, Shun Lu
Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) are standard treatment for advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation. However, EGFR mutation testing is not attainable in approximately 20% of patients. The current study examined intercalating and maintaining gefitinib treatment in stage IIIB/IV non-squamous NSCLC, never or former light smoking patients with unknown EGFR mutation status. Briefly, 219 patients who achieved stable disease (SD) with gemcitabine (1250 mg/m(2)) plus carboplatin (5 AUC) were randomized at 1:1 ratio to continue chemotherapy (n = 110) or intercalating gefitinib (250 mg/day on days 15-25 of each cycle until disease progress (n = 109)...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28809468/construction-of-supramolecular-drug-drug-delivery-system-for-non-small-cell-lung-cancer-therapy
#2
Zhihao Zhang, Leilei Shi, Chenwei Wu, Yue Su, Jiwen Qian, Hongping Deng, Xinyuan Zhu
Nanoscale drug delivery systems (DDSs) are generally considered to be an effective alternative to small molecular chemotherapeutics due to the improved accumulation in tumor site and enhanced retention in blood. Nevertheless, most of DDSs have low loading efficiency or even pose high threat to normal organs caused by severe side effects. Ideally, supramolecular drug-drug delivery system (SDDDS) made up of pure drugs via supramolecular interaction provides a hopeful solution for cancer treatment. Herein, we put forward a facile method to construct SDDDS via co-assembly of Gefitinib (GEF) and tripeptide tyroservatide (YSV), two kinds of chemotherapeutic pharmaceuticals for non-small cell lung cancer (NSCLC), via multiple intermolecular interactions, including hydrogen bond and π-π stacking...
August 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28795387/gefitinib-plus-fuzheng-kang-ai-formula-in-patients-with-advanced-non-small-cell-lung-cancer-with-epidermal-growth-factor-receptor-mutation-a-randomized-controlled-trial
#3
Xiao-Bing Yang, Xiao-Shu Chai, Wan-Yin Wu, Shun-Qin Long, Hong Deng, Zong-Qi Pan, Wen-Feng He, Yu-Shu Zhou, Gui-Ya Liao, Shu-Jing Xiao
OBJECTIVE: To evaluate the effect of Fuzheng Kang'ai Formula (, FZKA) plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations. METHODS: A randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage IIIB/IV non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefifitinib (250 mg/day orally) plus FZKA (250 mL, twice per day, orally); 35 cases] or G group (gefifitinib 250 mg/day orally; 35 cases) according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities...
August 9, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28794650/treating-egfr-mutation-resistance-in-non-small-cell-lung-cancer-role-of-osimertinib
#4
REVIEW
Valentina Mazza, Federico Cappuzzo
The discovery of mutations in EGFR significantly changed the treatment paradigm of patients with EGFR-mutant non-small cell lung cancer (NSCLC), a particular group of patients with different clinical characteristics and outcome to EGFR-wild-type patients. In these patients, the treatment of choice as first-line therapy is first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, or afatinib. Inevitably, after the initial response, all patients become refractory to these drugs...
2017: Application of Clinical Genetics
https://www.readbyqxmd.com/read/28781781/responses-to-crizotinib-and-chemotherapy-in-patients-with-lung-adenocarcinoma-harboring-a-concomitant-egfr-mutation-and-alk-gene-rearrangement-a-case-report-and-review-of-the-literature
#5
Yuping Li, Shanshan Su, Guoping Cai, Quan Lin, Ying Zhou, Jinsheng Ouyang, Bicheng Chen, Junru Ye, Xiuling Wu, Chengshui Chen
Previous studies have indicated that, in lung cancers, the gene rearrangement of ALK is mutually exclusive with mutations in the epidermal growth factor receptor (EGFR) gene. However, the coexistence of EML4-ALK fusions and EGFR mutations (double positive) has been occasionally reported, with frequencies ranging from 0-8%. Currently, no consensus standard therapy exists for tumors with double positive mutations. In the present case report, the case is described of a 53-year-old woman with stage IV lung adenocarcinoma, harboring a concomitant EGFR mutation and ALK gene rearrangement, who was refractory to gefitinib administration but demonstrated a good response to crizotinib and pemetrexed chemotherapy...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28761738/results-of-the-safety-run-in-part-of-the-metal-metformin-in-advanced-lung-cancer-study-a-multicentre-open-label-phase-i-ii-study-of-metformin-with-erlotinib-in-second-line-therapy-of-patients-with-stage-iv-non-small-cell-lung-cancer
#6
Floriana Morgillo, Morena Fasano, Carminia Maria Della Corte, Ferdinando Carlo Sasso, Federica Papaccio, Giuseppe Viscardi, Giovanna Esposito, Raimondo Di Liello, Nicola Normanno, Annalisa Capuano, Liberato Berrino, Giovanni Vicidomini, Alfonso Fiorelli, Mario Santini, Fortunato Ciardiello
PURPOSE: Our previous works demonstrated the ability of metformin to revert resistance to gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in non-small-cell lung cancer (NSCLC) EGFR/LKB1 wild-type (WT) cell lines. However, the optimal dose of metformin to be used in non-diabetic patients still remains to be defined. The phase I-II trial METformin in Advanced Lung cancer (METAL) was designed to identify the maximum tolerated dose and to evaluate safety and activity of metformin combined with erlotinib in second-line treatment of patients with stage IV NSCLC, whose tumours harbour the WT EGFR gene...
2017: ESMO Open
https://www.readbyqxmd.com/read/28761735/phase-iii-study-of-gefitinib-or-pemetrexed-with-carboplatin-in-egfr-mutated-advanced-lung-adenocarcinoma
#7
Vijay Maruti Patil, Vanita Noronha, Amit Joshi, Anuradha Bharat Choughule, Atanu Bhattacharjee, Rajiv Kumar, Supriya Goud, Sucheta More, Anant Ramaswamy, Ashay Karpe, Nikhil Pande, Arun Chandrasekharan, Alok Goel, Vikas Talreja, Abhishek Mahajan, Amit Janu, Nilendu Purandare, Kumar Prabhash
OBJECTIVE: Oral tyrosine kinase inhibitor has been shown to prolong progression-free survival (PFS) in estimated glomerular filtration rate (EGFR) mutation positive adenocarcinoma; however, the comparator arm has not included the current standard adenocarcinoma regimen (pemetrexed carboplatin induction followed by maintenance pemetrexed) and patients from Indian subcontinent. Hence, this study was carried out in Indian patients to compare gefitinib with the above-mentioned chemotherapy regimen...
2017: ESMO Open
https://www.readbyqxmd.com/read/28758931/tumor-stroma-crosstalk-in-bone-tissue-the-osteoclastogenic-potential-of-a-breast-cancer-cell-line-in-a-co-culture-system-and-the-role-of-egfr-inhibition
#8
Laura Mercatali, Federico La Manna, Giacomo Miserocchi, Chiara Liverani, Alessandro De Vita, Chiara Spadazzi, Alberto Bongiovanni, Federica Recine, Dino Amadori, Martina Ghetti, Toni Ibrahim
Although bone metastases represent a major challenge in the natural history of breast cancer (BC), the complex interactions involved have hindered the development of robust in vitro models. The aim of this work is the development of a preclinical model of cancer and bone stromal cells to mimic the bone microenvironment. We studied the effects on osteoclastogenesis of BC cells and Mesenchymal stem cells (MSC) cultured alone or in combination. We also analyzed: (a) whether the blockade of the Epithelial Growth Factor Receptor (EGFR) pathway modified their influence on monocytes towards differentiation, and (b) the efficacy of bone-targeted therapy on osteoclasts...
July 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28757192/delivery-of-epidermalgrowthfactor-receptor-inhibitor-via-a-customized-collagen-scaffold-promotes-meniscal-defect-regeneration-in-a-rabbit-model
#9
Zongyou Pan, Yan Wu, Xiaolei Zhang, Qianbao Fu, Jun Li, Yang Yang, Dongsheng Yu, Yuzi Xu, Xiaolang Lu, Heng Sun, Xianzhu Zhang, Boon Chin Heng, Varitsara Bunpetch, Shufang Zhang, Hongwei Ouyang
Meniscal injury is one of the most common knee joint injuries, which remains an intractable challenge in clinical practice to date. Aberrant epidermalgrowthfactor receptor (EGFR) activation levels in both human and mice menisci following injury, prompted us to investigate the functional role of EGFR by utilizing an inducible cartilage-specific EGFR-deficient mouse model. We demonstrated that conditional EGFR deletion in mice resulted in increased partial meniscectomy-induced ECM production within the meniscus, which is comparable to utilization of the small molecule EGFR inhibitor, gefitinib, to block EGFR activity...
July 27, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28757172/polyphyllin-vii-increases-sensitivity-to-gefitinib-by-modulating-the-elevation-of-p21-in-acquired-gefitinib-resistant-non-small-cell-lung-cancer
#10
Honggang Wang, Zhenghua Fei, Hao Jiang
Blockade of EGFR with reversible EGFR tyrosine kinase inhibitors (TKIs) is considered the frontline strategy for advanced NSCLC with EGFR mutations. However, acquired resistance to EGFR-TKI has been observed, resulting in disease progression and limited clinical benefit. Polyphyllin VII is the main member of polyphyllin family, which has been demonstrated to show strong anticancer activity against carcinomas. The sensitizing effect and underlying mechanism of Polyphyllin VII against acquired EGFR-TKI resistant NSCLC are still unexplored...
June 30, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28756224/treatment-with-a-programmed-cell-death-1-specific-antibody-has-little-effect-on-afatinib-and-naphthalene-induced-acute-pneumonitis-in-mice
#11
Naoki Hamada, Toyoshi Yanagihara, Kunihiro Suzuki, Saiko Ogata-Suetsugu, Eiji Harada, Hironori Mikumo, Masako Arimura-Omori, Yoichi Nakanishi
Although several antibodies developed to target programmed cell death-1 (PD-1) and its ligand (PD-L1) have demonstrated great promise for the treatment of non-small cell lung cancer (NSCLC), and other malignancies, these therapeutic antibodies can cause pneumonitis. Furthermore, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-induced pneumonitis was reported after treatment with anti PD-1 antibodies. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis through a neutrophil-dependent mechanism...
July 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28754471/how-to-train-your-inhibitor-design-strategies-to-overcome-resistance-to-epidermal-growth-factor-receptor-inhibitors
#12
REVIEW
Sandra N Milik, Deena S Lasheen, Rabah A T Serya, Khaled A M Abouzid
Epidermal Growth Factor Receptor (EGFR) stands out as a key player in the development of many cancers. Its dysregulation is associated with a vast number of tumors such as non-small-cell lung cancer, colon cancer, head-and-neck cancer, breast and ovarian cancer. Being implicated in the development of a number of the most lethal cancers worldwide, EGFR has long been considered as a focal target for cancer therapies, ever since the FDA approval of "Gefitinib" in 2003 and up to the last FDA approved small molecule EGFR kinase inhibitor "Osimertinib" in 2015...
July 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28753272/colony-lysate-arrays-for-proteomic-profiling-of-drug-tolerant-persisters-of-cancer-cell
#13
Kohei Kume, Satoshi S Nishizuka
Functional heterogeneity of cancer cells is one of the key properties to understanding relapse after drug treatment. Hence, clarification is needed with regard to which types of subgroups of cancer cells dominantly contribute to the initiation of relapse. Recently, we established the colony lysate array (CoLA), which is a method that allows comparison of individual colonies at the protein level to assess the initiation of anticancer drug-tolerant persisters (DTPs) based on the reverse-phase protein array (RPPA) system...
August 11, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28751244/cost-effectiveness-analysis-of-afatinib-versus-gefitinib-for-first-line-treatment-of-advanced-egfr-mutated-advanced-non-small-cell-lung-cancers
#14
Christos Chouaid, Laura Luciani, Katell LeLay, Pascal Do, Jaafar Bennouna, Maurice Perol, Denis Moro-Sibilot, Alain Vergnengre, Gérard de Pouvourville
BACKGROUND: The irreversible ErbB-family-blocker afatinib and the reversible EGFR tyrosine-kinase-inhibitor gefitinib were compared in the multicenter, international, randomized, head-to-head phase-2b LUX-Lung 7 trial for first-line treatment of advanced EGFR-mutation-positive non-small-cell lung cancers (EGFRm+ NSCLCs). Afatinib and gefitinib costs and patients' outcomes in France were assessed. METHODS: A partitioned survival model was designed to assess the cost-effectiveness of afatinib vs...
July 24, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28749011/simultaneous-quantification-of-volitinib-and-gefitinib-in-rat-plasma-by-hplc-ms-ms-for-application-to-a-pharmacokinetic-study-in-rats
#15
Chi-Kyoung Noh, Jong-Hwa Lee, Min-Soo Kim, Han-Joo Maeng, Suk-Jae Chung
A rapid, simple and accurate procedure was developed and validated for the simultaneous quantification of two anticancer agents, volitinib and gefitinib in rat plasma by high-performance liquid chromatography with tandem mass spectrometry. The samples were separated by gradient elution from a CN column within five minutes, using 0.1% formic acid in acetonitrile and 10 mM ammonium formate solution (pH 3.0) as mobile phase. When plasma samples were deproteinated by adding methanol, the analytes in the extract were detected in the positive ionization mode with the tracer ion mass of 346...
July 27, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28748556/systemic-therapy-treatment-patterns-in-patients-with-advanced-non-small-cell-lung-cancer-nsclc-pivotal-study
#16
J de Castro, P Tagliaferri, V C C de Lima, S Ng, M Thomas, A Arunachalam, X Cao, S Kothari, T Burke, H Myeong, A Grattan, D H Lee
The aim of this multinational retrospective cohort study, conducted at academic and community oncology centres, was to describe real-world treatment patterns for patients with a confirmed diagnosis of advanced/metastatic (stage IIIB/IV) non-small cell lung cancer (NSCLC) who initiated first-line systemic therapy from January 2011 through June 2014. The study included 1265 patients in Italy, Spain, Germany, Australia, Korea, Taiwan and Brazil. The proportion of patients with squamous versus non-squamous NSCLC was approximately 20% versus 75%, and associated patient demographic characteristics were similar in all countries, excepting race...
July 27, 2017: European Journal of Cancer Care
https://www.readbyqxmd.com/read/28747773/deciphering-mechanisms-of-acquired-t790m-mutation-after-egfr-inhibitors-for-nsclc-by-computational-simulations
#17
Bin Zou, Victor H F Lee, Lijiang Chen, Lichun Ma, Debby D Wang, Hong Yan
Metastatic non-small-cell lung cancer (NSCLC) with activating EGFR mutations responds very well to first and second generation tyrosine-kinase inhibitors (TKI) including gefitinib, erlotinib and afatinib. Unfortunately, drug resistance will eventually develop and about half of the cases are secondary to the emergence of acquired T790M somatic mutation. In this work, we prospectively recruited 68 patients with metastatic EGFR-mutated NSCLC who have developed progressive disease after first-line TKI with or without subsequent TKI and/or other systemic therapy...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747569/acquisition-of-the-t790m-resistance-mutation-during-afatinib-treatment-in-egfr-tyrosine-kinase-inhibitor-na%C3%A3-ve-patients-with-non-small-cell-lung-cancer-harboring-egfr-mutations
#18
Kentaro Tanaka, Kaname Nosaki, Kohei Otsubo, Koichi Azuma, Shinya Sakata, Hiroshi Ouchi, Ryotaro Morinaga, Hiroshi Wataya, Akiko Fujii, Noriaki Nakagaki, Nobuko Tsuruta, Masafumi Takeshita, Eiji Iwama, Taishi Harada, Yoichi Nakanishi, Isamu Okamoto
The T790M secondary mutation of the epidermal growth factor receptor (EGFR) gene accounts for 50% to 60% of cases of resistance to the first-generation EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. The prevalence of T790M in EGFR mutation-positive patients who acquire resistance to the irreversible, second-generation EGFR-TKI afatinib has remained unclear, however. We here determined the frequency of T790M acquisition at diagnosis of progressive disease in patients with EGFR-mutated non-small cell lung cancer (NSCLC) treated with afatinib as first-line EGFR-TKI...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28740693/disease-flare-after-discontinuing-gefitinib-in-a-patient-with-lung-adenocarcinoma-and-concomitant-epithelial-growth-factor-receptor-mutation-and-anaplastic-lymphoma-kinase-translocation
#19
Eun Hye Park, Hwa Young Lee, Jin Woo Kim, Chang Dong Yeo
We report on a patient with lung adenocarcinoma and a concomitant epithelial growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation who developed a disease flare after discontinuing gefitinib. A 63-year-old woman with lung adenocarcinoma and a concomitant activating EGFR mutation and ALK translocation was treated with first-line gefitinib. After 4 months, she discontinued the gefitinib due to disease progression. She was admitted to the emergency room complaining of severe dyspnea and back pain 22 days after discontinuing gefitinib...
June 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28731495/significance-of-neutrophil-to-lymphocyte-ratio-in-western-advanced-egfr-mutated-non-small-cell-lung-cancer-receiving-a-targeted-therapy
#20
Fausto Meriggi, Claudio Codignola, Giordano D Beretta, Giovanni L Ceresoli, Alberto Caprioli, Mario Scartozzi, Anna P Fraccon, Tiziana Prochilo, Chiara Ogliosi, Alberto Zaniboni
PURPOSE: Lung cancer is one of the leading causes of cancer-related death worldwide and, although targeted therapy with tyrosine kinase inhibitors has dramatically improved the rates of response and survival in advanced EGFR-mutated adenocarcinoma, the overall outcome remains unsatisfactory. Therefore, new prognostic factors, preferably simple, inexpensive, and easy to reproduce on a large scale, are needed. We performed a retrospective analysis of our database including 63 western Caucasian patients with advanced EGFR-mutated lung adenocarcinoma and receiving gefitinib, erlotinib, or afatinib as first- or second-line therapy...
July 14, 2017: Tumori
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