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https://www.readbyqxmd.com/read/28816950/pemetrexed-carboplatin-with-intercalated-icotinib-in-the-treatment-of-patient-with-advanced-egfr-wild-type-lung-adenocarcinoma-a-case-report
#1
Tongpeng Xu, Hao Wu, Shidai Jin, Huang Min, Zhihong Zhang, Yongqian Shu, Wei Wen, Renhua Guo
RATIONALE: Tyrosine kinase inhibitors (TKIs) are known to have greater efficacy in epidermal growth factor receptor (EGFR) mutation nonsmall cell lung cancer (NSCLC). However, about 10% of EGFR wild-type (wt) patients respond to TKIs. PATIENT CONCERNS: Several strategies to increase the efficacy of TKIs in wt NSCLC are the subjects of ongoing investigations. One of them is combining EGFR TKI with intercalated chemotherapy. DIAGNOSES: We describe a patient with EGFR wt NSCLC, who was found with ovarian and lung metastasis, was treated with pemetrexed and intercalated icotinib...
August 2017: Medicine (Baltimore)
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
#2
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/28812918/tyrosine-kinase-inhibitors-for-advanced-or-metastatic-thyroid-cancer-a-meta-analysis-of-randomized-controlled-trials
#3
Jen-Wei Liu, Chiehfeng Chen, El-Wui Loh, Chun-Cheng Chu, Mu-Yi Wang, Hsin-Ju Ouyang, Ya-Ting Chang, Wei-Zhan Zhuang, Ching-Wen Chou, Der-Jr Huang, Chia-Hwa Lee, Yun Yen, Ka-Wai Tam
BACKGROUND AND AIMS: Radioiodine-refractory advanced or metastatic thyroid cancer has poor prognosis. We conducted a meta-analysis of randomized controlled trials to evaluate the effectiveness and safety of tyrosine kinase inhibitors (TKIs) for advanced or metastatic thyroid cancer treatment. METHODS: Studies published until April 2017 were selected. The pooled effect size was calculated through meta-analysis by using random effects models. Outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (RR), and adverse events (AEs)...
August 16, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28808483/therapeutic-immune-monitoring-of-cd4-cd25-t-cells-in-chronic-myeloid-leukemia-patients-treated-with-tyrosine-kinase-inhibitors
#4
Ziyuan Lu, Na Xu, Xuan Zhou, Guanlun Gao, Lin Li, Jixian Huang, Yuling Li, Qisi Lu, Bolin He, Chengyun Pan, Xiaoli Liu
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib, are effective forms of therapy for various types of solid cancers and Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia. A number of TKIs have been known to have strong effects on T cells, particularly cluster of differentiation (CD) 4(+)CD25(+) T cells, also known as regulatory T cells (Tregs). There is currently a deficit in the available clinical data regarding this area of study. In the present study, a total of 108 peripheral blood samples were collected from patients with chronic myeloid leukemia (CML) at diagnosis (n=31), and at 3 and 6 months following treatment with TKI [imatinib (n=12), dasatinib (n=11) and nilotinib groups (n=8)] and healthy controls (n=15)...
August 2017: Oncology Letters
https://www.readbyqxmd.com/read/28807234/third-generation-egfr-tkis-in-egfr-mutated-nsclc-where-are-we-now-and-where-are-we-going
#5
REVIEW
A Russo, T Franchina, G R R Ricciardi, V Smiroldo, M Picciotto, M Zanghì, C Rolfo, V Adamo
The therapeutic landscape of Non Small Lung Cancer (NSCLC) has been profoundly changed over the last decade with the clinical introduction of Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) and the discovery of EGFR activating mutations as the major predictive factor to these agents. Despite impressive clinical activity against EGFR-mutated NSCLCs, the benefit seen with 1st and 2nd generation EGFR TKIs is usually transient and virtually all patients become resistant. Several different mechanisms of acquired resistance have been reported to date, but the vast majority of patients develop a secondary exon 20 mutation in the ATP-binding site of EGFR, namely T790M...
September 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28806542/outcome-of-patients-with-lung-adenocarcinoma-with-transformation-to-small-cell-lung-cancer-following-tyrosine-kinase-inhibitors-treatment-a-systematic-review-and-pooled-analysis
#6
REVIEW
Elisa Roca, Cristina Gurizzan, Vito Amoroso, William Vermi, Vittorio Ferrari, Alfredo Berruti
BACKGROUND: Lung adenocarcinoma can transform to small-cell lung cancer (SCLC) when resistance to tyrosine kinase inhibitors (TKIs) develops. This phenomenon has repeatedly been described in several case reports and small patient series. The characteristics and treatment outcomes of this population, however, have not been comprehensively reported. METHODS: We performed a systematic review of the published literature to obtain explorative information on the clinical and pathological features and prognosis of the reported cases...
July 31, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28801986/persistent-detection-of-alternatively-spliced-bcr-abl-variant-results-in-a-failure-to-achieve-deep-molecular-response
#7
Junichiro Yuda, Toshihiro Miyamoto, Jun Odawara, Yasuyuki Ohkawa, Yuichiro Semba, Masayasu Hayashi, Koichi Miyamura, Mitsune Tanimoto, Kazuhito Yamamoto, Masafumi Taniwaki, Koichi Akashi
Treatment with tyrosine kinase inhibitors (TKIs) may sequentially induce TKI-resistant BCR-ABL mutants in chronic myeloid leukemia (CML). Conventional polymerase chain reaction (PCR) monitoring of BCR-ABL is an important indicator to determine therapeutic intervention for preventing disease progression. However, PCR cannot quantify separately amounts of BCR-ABL and its mutants, including alternatively spliced BCR-ABL with an insertion of 35 intronic nucleotides (BCR-ABL(I)(ns35bp) ) between ABL exons 8 and 9 which introduces the premature termination and loss of kinase activity...
August 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28801183/paired-phase-ii-studies-of-erlotinib-bevacizumab-for-advanced-bronchioloalveolar-carcinoma-or-never-smokers-with-advanced-non-small-cell-lung-cancer-swog-s0635-and-s0636-trials
#8
Howard L West, James Moon, Antoinette J Wozniak, Philip Mack, Fred R Hirsch, Martin J Bury, Myron Kwong, Dorothy D Nguyen, Dennis F Moore, Jieling Miao, Mary Redman, Karen Kelly, David R Gandara
BACKGROUND: Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636)...
July 6, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28798090/egfr-tyrosine-kinase-inhibitors-versus-chemotherapy-in-egfr-wild-type-pre-treated-advanced-nonsmall-cell-lung-cancer-in%C3%A2-daily-practice
#9
Pascale Tomasini, Solenn Brosseau, Julien Mazières, Jean-Philippe Merlio, Michèle Beau-Faller, Jean Mosser, Marie Wislez, L'Houcine Ouafik, Benjamin Besse, Isabelle Rouquette, Didier Debieuvre, Fabienne Escande, Virginie Westeel, Clarisse Audigier-Valette, Pascale Missy, Alexandra Langlais, Frank Morin, Denis Moro-Sibilot, Gérard Zalcman, Fabrice Barlesi
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are approved for second-line treatment of EGFR wild-type (EGFR-wt) nonsmall cell lung cancer (NSCLC). However, results from randomised trials performed to compare EGFR-TKIs with chemotherapy in this population did not show any survival benefit. In the era of immunotherapy, many drugs are approved for second-line treatment of EGFR-wt NSCLC and there is a need to reassess the role of EGFR-TKIs in this setting.The Biomarkers France study is a large nationwide cohort of NSCLC patients tested for EGFR mutations...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28794650/treating-egfr-mutation-resistance-in-non-small-cell-lung-cancer-role-of-osimertinib
#10
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/28791656/egfr-as-a-target-for-glioblastoma-treatment-an-unfulfilled-promise
#11
Manfred Westphal, Cecile L Maire, Katrin Lamszus
The receptor for epidermal growth factor (EGFR) is a prime target for cancer therapy across a broad variety of tumor types. As it is a tyrosine kinase, small molecule tyrosine kinase inhibitors (TKIs) targeting signal transduction, as well as monoclonal antibodies against the EGFR, have been investigated as anti-tumor agents. However, despite the long-known enigmatic EGFR gene amplification and protein overexpression in glioblastoma, the most aggressive intrinsic human brain tumor, the potential of EGFR as a target for this tumor type has been unfulfilled...
August 8, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28790845/clinical-efficacy-evaluation-of-tyrosine-kinase-inhibitors-for-non-adenocarcinoma-lung-cancer-patients-harboring-egfr-sensitizing-mutations
#12
REVIEW
Xinyu Song, Zhehai Wang
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as a standard therapy have been used in EGFR-mutated adenocarcinoma of non-small-cell lung cancer (NSCLC) patients in recent years. But in current randomized prospective clinical trials, due to few cases of non-adenocarcinoma patients having been found, the efficacy of TKIs for EGFR-mutated non-adenocarcinoma and the relationship with clinicopathological characteristics remained debatable. The results of retrospective studies showed that the frequency of EGFR mutation was significantly associated with nationality, gender, smoking history, and histology type...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28778092/epidermal-growth-factor-receptor-t790m-mutation-as-a-prognostic-factor-in-egfr-mutant-non-small-cell-lung-cancer-patients-that-acquired-resistance-to-egfr-tyrosine-kinase-inhibitors
#13
Guangzhi Ma, Jing Zhang, Hai Jiang, Nannan Zhang, Liyuan Yin, Wen Li, Qinghua Zhou
Epidermal growth factor receptor (EGFR) T790M mutation accounted for over half of drug resistance cases in EGFR-mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) and led to different outcomes. This study aimed to assess the prognostic role of T790M in NSCLC patients treated with EGFR-TKIs that developed drug resistance. Eligible literatures were reviewed from various databases and a meta-analysis was performed to evaluate the prognostic role of T790M mutation in EGFR-TKIs treated patients that went progression...
July 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28777825/beyond-disease-progression-clinical-outcomes-after-egfr-tkis-in-a-cohort-of-egfr-mutated-nsclc-patients
#14
Roxana Alina Tudor, Adrijana D'Silva, Alain Tremblay, Paul MacEachern, Don Morris, Darren Brenner, Karen Kopciuk, Dafydd Gwyn Bebb
PURPOSE: Treatment and clinical-outcomes were described in a sub-cohort of non-small-cell lung cancer (NSCLC) patients with disease-progression (PD) after epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) treatment. PATIENTS AND METHODS: We retrospectively analyzed a single-institutional EGFR mutation positive (EGFRmut+) NSCLC cohort for post-TKI-PD management, and assessed overall survival (OS) and post-progression survival (PPS). All de-novo (first lung-cancer occurrence) stage IIIA-IV patients, as well as de-novo stage IV subset was analyzed...
2017: PloS One
https://www.readbyqxmd.com/read/28774798/drug-combination-approach-to-overcome-resistance-to-egfr-tyrosine-kinase-inhibitors-in-lung-cancer
#15
Christy W S Tong, William K K Wu, Herbert H F Loong, William C S Cho, Kenneth K W To
The discovery of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) has led to unprecedented clinical response in a subset of lung cancer patients carrying the sensitizing EGFR mutations (L858R or exon 19 deletion). However, disease progression invariably occurs within a year after the initial TKI treatment, predominantly due to the development of acquired resistance caused by the secondary EGFR T790 M mutation. Numerous second generation irreversible and third generation EGFR T790 M selective EGFR TKIs have been developed to overcome resistance...
July 31, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28774214/the-safety-of-bosutinib-for-the-treatment-of-chronic-myeloid-leukemia
#16
Jee Hyun Kong, H J Khoury, Audrey Sunwha Kim, Brittany Gray Hill, Vamsi Kota
Introduction Tyrosine kinase inhibitors (TKIs) are a potentially lifelong treatment for patients with chronic myeloid leukemia (CML). Adverse events (AEs) associated with TKIs are significant impediments in the daily life of patients that can impact compliance, and efficacy. Areas covered This is a review on safety of bosutinib in the treatment of chronic phase CML. Data is extracted from the latest updates of bosutinib phase I/II and III trials. Expert opinion Bosutinib is an effective agent against all phases of CML presently approved for the treatment in patients with resistance or intolerance to prior TKI therapy...
August 3, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28772207/bone-marrow-mesenchymal-stromal-cell-msc-gene-profiling-in-chronic-myeloid-leukemia-cml-patients-at-diagnosis-and-in-deep-molecular-response-induced-by-tyrosine-kinase-inhibitors-tkis
#17
Djamel Aggoune, Nathalie Sorel, Marie-Laure Bonnet, Jean-Michel Goujon, Karin Tarte, Olivier Hérault, Jorge Domenech, Delphine Réa, Laurence Legros, Hyacinthe Johnson-Ansa, Philippe Rousselot, Emilie Cayssials, Agnès Guerci-Bresler, Annelise Bennaceur-Griscelli, Jean-Claude Chomel, Ali G Turhan
Although it has been well-demonstrated that bone marrow mesenchymal stromal cells (MSCs) from CML patients do not belong to the Ph1-positive clone, there is growing evidence that they could play a role in the leukemogenesis process or the protection of leukemic stem cells from the effects of tyrosine kinase inhibitors (TKIs). The aim of the present study was to identify genes differentially expressed in MSCs isolated from CML patients at diagnosis (CML-MSCs) as compared to MSCs from healthy controls. Using a custom gene-profiling assay, we identified six genes over-expressed in CML-MSCs (BMP1, FOXO3, MET, MITF, NANOG, PDPN), with the two highest levels being documented for PDPN (PODOPLANIN) and NANOG...
July 26, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28770623/angiogenesis-inhibitors-in-early-development-for-gastric-cancer
#18
Mauricio P Pinto, Gareth I Owen, Ignacio Retamal, Marcelo Garrido
Angiogenesis, or the generation of new blood vessels from pre-existent ones is a critical process for tumor growth and progression. Hence, the development of angiogenesis inhibitors with therapeutic potential has been a central focus for researchers. Most angiogenesis inhibitors target the Vascular Endothelial Growth Factor (VEGF) pathway, however a number of tyrosine kinase inhibitors (TKIs), immunomodulatory drugs (IMiDs) and inhibitors of the mammalian Target-Of-Rapamycin (mTOR) pathway also display antiangiogenic activity...
August 3, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28767402/mimicking-the-bim-bh3-domain-overcomes-resistance-to-egfr-tyrosine-kinase-inhibitors-in-egfr-mutant-non-small-cell-lung-cancer
#19
Jinjing Xia, Hao Bai, Bo Yan, Rong Li, Minhua Shao, Liwen Xiong, Baohui Han
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are widely applied to treat EGFR-mutant non-small cell lung cancer (NSCLC). BIM is a BH3 domain-containing protein encoded by BCL2L11. Some EGFR-mutant NSCLC patients showing BIM deletion polymorphism are resistant to EGFR TKIs. We retrospectively investigated BIM deletion polymorphism in NSCLC patients, its correlation with EGFR TKI (erlotinib) resistance, and the mechanism underlying the drug resistance. Among 245 EGFR-mutant NSCLC patients examined, BIM deletion polymorphism was detected in 43 (12...
July 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28762388/improving-outcomes-in-high-risk-nonmetastatic-renal-cancer-new-data-and-ongoing-trials
#20
REVIEW
Chris Blick, Alastair W S Ritchie, Timothy Eisen, Grant D Stewart
High-risk, localized renal cancer is associated with recurrence rates of up to 75% at 10 years. The outcomes of patients at this disease stage depend on optimal patient stratification, surgical management and systemic therapy selection. Current evidence does not support the use of adjuvant therapy in patients with high-risk, localized disease. During the past 12 months, the results of large, randomized-controlled trials of adjuvant tyrosine kinase inhibitor (TKI) treatment, such as ASSURE and S-TRAC, have been published, but their findings are conflicting...
August 1, 2017: Nature Reviews. Urology
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