keyword
MENU ▼
Read by QxMD icon Read
search

Dacomitinib

keyword
https://www.readbyqxmd.com/read/28592399/dacomitinib-beats-gefitinib-for-egfr-nsclc
#1
(no author information available yet)
The irreversible EGFR inhibitor dacomitinib reduced the chance of lung cancer progression compared with an older, first-generation EGFR inhibitor, gefitinib, in a phase III trial. As reported at the 2017 American Society of Clinical Oncology Annual Meeting, the experimental drug also increased toxicity, which could limit its use, especially with a safer, more effective third-generation EGFR inhibitor not far behind in the development pipeline.
June 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28575464/phase-ii-trial-of-dacomitinib-a-pan-her-human-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-in-recurrent-glioblastoma-patients-with-egfr-amplification
#2
Juan Manuel Sepúlveda-Sánchez, María Ángeles Vaz, Carmen Balañá, Miguel Gil-Gil, Gaspar Reynés, Óscar Gallego, María Martínez-García, Elena Vicente, María Quindós, Raquel Luque, Ana Ramos, Yolanda Ruano, Pedro Pérez-Segura, Manuel Benavides, Pilar Sánchez-Gómez, Aurelio Hernández-Laín
Background.: We conducted a multicenter, 2-stage, open-label, phase II trial to assess the efficacy and safety of dacomitinib in adult patients with recurrent glioblastoma (GB) and epidermal growth factor receptor (EGFR) gene amplification with or without EGFRvIII deletion. Methods.: Patients with first recurrence were enrolled in two cohorts: Cohort A) patients with EGFR gene amplification without EGFRvIII mutation; Cohort B) patients with EGFR gene amplification and EGFRvIII mutation...
June 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28462807/therapeutic-efficacy-comparison-of-5-major-egfr-tkis-in-advanced-egfr-positive-non-small-cell-lung-cancer-a-network-meta-analysis-based-on-head-to-head-trials
#3
Yaxiong Zhang, Zhonghan Zhang, Xiaodan Huang, Shiyang Kang, Gang Chen, Manli Wu, Siyu Miao, Yan Huang, Hongyun Zhao, Li Zhang
BACKGROUND: Five major first- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including erlotinib, gefitinib, icotinib, afatinib, and dacomitinib, are currently optional for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, there was no head-to-head-based network meta-analysis among all the TKIs in EGFR-mutated populations. METHODS: Eligible literature was searched from an electronic database...
October 27, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28424775/second-line-treatment-of-non-small-cell-lung-cancer-focus-on-the-clinical-development-of-dacomitinib
#4
REVIEW
Jon Zugazagoitia, Asunción Díaz, Elisabeth Jimenez, Juan Antonio Nuñez, Lara Iglesias, Santiago Ponce-Aix, Luis Paz-Ares
Dacomitinib is a second-generation, irreversible, covalent pan-HER tyrosine-kinase inhibitor (TKI). It showed potent EGFR signaling inhibition in experimental models, including first-generation TKI-resistant non-small cell lung cancer (NSCLC) cell lines. This preclinical efficacy did not translate into clinically meaningful treatment benefits for advanced, pretreated, molecularly unselected NSCLC patients enrolled in two parallel phase III trials. Dacomitinib and erlotinib showed overlapping efficacy data in chemotherapy-pretreated EGFR wild-type (WT) patients in the ARCHER 1009 trial...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28394918/a-novel-technique-of-serial-biopsy-in-mouse-brain-tumour-models
#5
Sasha Rogers, Hilary Hii, Joel Huang, Mathew Ancliffe, Nick G Gottardo, Peter Dallas, Sharon Lee, Raelene Endersby
Biopsy is often used to investigate brain tumour-specific abnormalities so that treatments can be appropriately tailored. Dacomitinib (PF-00299804) is a tyrosine kinase inhibitor (TKI), which is predicted to only be effective in cancers where the targets of this drug (EGFR, ERBB2, ERBB4) are abnormally active. Here we describe a method by which serial biopsy can be used to validate response to dacomitinib treatment in vivo using a mouse glioblastoma model. In order to determine the feasibility of conducting serial brain biopsies in mouse models with minimal morbidity, and if successful, investigate whether this can facilitate evaluation of chemotherapeutic response, an orthotopic model of glioblastoma was used...
2017: PloS One
https://www.readbyqxmd.com/read/28363995/response-heterogeneity-of-egfr-and-her2-exon-20-insertions-to-covalent-egfr-and-her2-inhibitors
#6
Takayuki Kosaka, Junko Tanizaki, Raymond M Paranal, Hideki Endoh, Christine Lydon, Marzia Capelletti, Claire E Repellin, Jihyun Choi, Atsuko Ogino, Antonio Calles, Dalia Ercan, Amanda J Redig, Magda Bahcall, Geoffrey R Oxnard, Michael J Eck, Pasi A Jänne
Insertion mutations in EGFR and HER2 both occur at analogous positions in exon 20. Non-small cell lung cancer (NSCLC) patients with tumors harboring these mutations seldom achieve clinical responses to dacomitinib and afatinib, two covalent quinazoline-based inhibitors of EGFR or HER2, respectively. In this study, we investigated the effects of specific EGFR and HER2 exon 20 insertion mutations from NSCLC patients that had clinically achieved a partial response after dacomitinib treatment. We identified Gly770 as a common feature among the drug-sensitive mutations...
May 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28359250/insight-into-discovery-of-next-generation-reversible-tmlr-inhibitors-targeting-egfr-activating-and-drug-resistant-t790m-mutants
#7
Subhash Mohan Agarwal, Divyani Pal, Mansi Gupta, Ravi Saini
Cancer is one of the most challenging diseases among the various causes of deaths worldwide. Among cancer, lung cancer rules as the leading cause of cancer-related deaths annually.The majority of the lung cancers identified are non-small cell lung cancer (NSCLC). Clinically, the Epidermal Growth Factor Receptor (EGFR) is a therapeutically accepted target for NSCLC. Many therapeutic leads that target this transmembrane receptor protein were tested for anti-EGFR activity that led to the discovery of gefitinib and erlotinib...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28339087/regulation-of-intestinal-myofibroblasts-by-kras-mutated-colorectal-cancer-cells-through-heparin-binding-epidermal-growth-factor-like-growth-factor
#8
Hideyoshi Kawasaki, Takuya Saotome, Tatsuya Usui, Takashi Ohama, Koichi Sato
In colorectal cancer, gain-of-function mutations in KRas play a critical role in malignant transformation. Tumor growth in colorectal cancer is known to be promoted by the intestinal myofibroblasts (IMFs) that localize adjacent to the cancer cells, but the mechanisms of interaction between KRas-mutated cancer cells and the myofibroblasts remain unclear. Here, we investigated the effects of KRas-mutated cells on the behavior of myofibroblasts by using mouse primary IMFs and cells of an IMF cell line (LmcMF) and a mouse colon epithelial cell line (aMoC1)...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28316082/dacomitinib-induced-diarrhoea-is-associated-with-altered-gastrointestinal-permeability-and-disruption-in-ileal-histology-in-rats
#9
Ysabella Z A Van Sebille, Rachel J Gibson, Hannah R Wardill, Kate R Secombe, Imogen A Ball, Dorothy M K Keefe, John W Finnie, Joanne M Bowen
Dacomitinib-an irreversible pan-ErbB tyrosine kinase inhibitor (TKI)-causes diarrhoea in 75% of patients. Dacomitinib-induced diarrhoea has not previously been investigated and the mechanisms remain poorly understood. The present study aimed to develop an in-vitro and in-vivo model of dacomitinib-induced diarrhoea to investigate underlying mechanisms. T84 cells were treated with 1-4 μM dacomitinib and resistance and viability were measured using transepithelial electrical resistance (TEER) and XTT assays. Rats were treated with 7...
March 17, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28285698/impact-of-a-planned-dose-interruption-of-dacomitinib-in-the-treatment-of-advanced-non-small-cell-lung-cancer-archer-1042
#10
Dong-Wan Kim, Edward B Garon, Aminah Jatoi, Dorothy M Keefe, Mario E Lacouture, Stephen Sonis, Diana Gernhardt, Tao Wang, Nagdeep Giri, Jim P Doherty, Sashi Nadanaciva, Joseph O'Connell, Eric Sbar, Byoung Chul Cho
OBJECTIVES: Dacomitinib is a pan-HER inhibitor for advanced non-small-cell lung cancer (NSCLC). We explored the impact of a planned 4-day dacomitinib dose interruption on plasma exposure of dacomitinib and adverse events (AEs) of interest in Cohort III of the ARCHER 1042 study. MATERIALS AND METHODS: Patients, treatment-naïve for advanced NSCLC with EGFR activating mutations, received oral dacomitinib 45mg QD (once daily). A planned dose interruption occurred in Cycle 1 from Days 11 through 14...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28009971/dacomitinib-a-new-pan-egfr-inhibitor-is-effective-in-killing-ovarian-cancer-cells
#11
Lei Xu, Huini Wu, Chao Jiang, Hongcai Wang, Bei Gao, Shumei Yan, Yushu Qi, Shufeng Zhou
OBJECTIVE: Aberrant epidermal growth factor receptor (EGFR) is involved in a variety of cancers and its inhibitors have been studied for over a decade. We aim to investigate the effects of dacomitinib, a second generation pan-EGFR inhibitor, on ovarian cancer cells. METHODS: By immunohistochemistry, we studied the clinical significance of EGFR expression in epithelial ovarian cancer (EOC). The correlations between EGFR expression and the clinicopathological variables of patients with EOC were assessed using Pearson's X2 test...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27920501/three-generations-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-developed-to-revolutionize-the-therapy-of-lung-cancer
#12
REVIEW
Haijun Zhang
Lung cancer, ~80%-85% of which is non-small-cell lung cancer (NSCLC), is the leading cause of cancer-related mortality worldwide. Sensitizing mutations in epidermal growth factor receptor (EGFR) gene (EGFRm(+)), such as exon 19 deletions and exon 21 L858R point mutations, are the most important drivers in NSCLC patients. In this respect, small-molecule EGFR tyrosine kinase inhibitors (TKIs) have been designed and developed, which launched the era of targeted, personalized and precise medicine for lung cancer...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27913578/characterization-of-egfr-t790m-l792f-and-c797s-mutations-as-mechanisms-of-acquired-resistance-to-afatinib-in-lung-cancer
#13
Yoshihisa Kobayashi, Koichi Azuma, Hiroki Nagai, Young Hak Kim, Yosuke Togashi, Yuichi Sesumi, Masato Chiba, Masaki Shimoji, Katsuaki Sato, Kenji Tomizawa, Toshiki Takemoto, Kazuto Nishio, Tetsuya Mitsudomi
Lung cancers harboring common EGFR mutations respond to EGFR tyrosine kinase inhibitors (TKI). We previously reported that tumors with exon 18 mutations are particularly sensitive to irreversible second-generation (2G) afatinib compared with first-generation TKIs (1G-TKI). However, data on the mechanisms of acquired resistance to afatinib are limited. We established afatinib-resistant cells by transfecting Ba/F3 cells with common or exon 18 (G719A and Del18) mutations and subjecting them to chronic exposure to increasing concentrations of afatinib...
February 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27733479/a-phase-i-clinical-trial-and-independent-patient-derived-xenograft-study-of-combined-targeted-treatment-with-dacomitinib-and-figitumumab-in-advanced-solid-tumors
#14
Emiliano Calvo, Jean-Charles Soria, Wen Wee Ma, Tao Wang, Rastilav Bahleda, Anthony W Tolcher, Diana Gernhardt, Joseph O'Connell, Robert Millham, Nagdeep Giri, Michael J Wick, Alex A Adjei, Manuel Hidalgo
Purpose: This phase I, open-label, single-arm trial assessed the safety and tolerability of dacomitinib-figitumumab combination therapy in patients with advanced solid tumors.Experimental Design: A standard 3 + 3 dose escalation/de-escalation design was utilized. Starting doses were figitumumab 20 mg/kg administered intravenously once every 3 weeks and dacomitinib 30 mg administered orally once daily. We also performed an independent study of the combination in patient-derived xenograft (avatar mouse) models of adenoid cystic carcinoma...
March 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27678331/ibrutinib-inhibits-erbb-receptor-tyrosine-kinases-and-her2-amplified-breast-cancer-cell-growth
#15
Jun Chen, Taisei Kinoshita, Juthamas Sukbuntherng, Betty Y Chang, Laurence Elias
Ibrutinib is a potent, small-molecule Bruton tyrosine kinase (BTK) inhibitor developed for the treatment of B-cell malignancies. Ibrutinib covalently binds to Cys481 in the ATP-binding domain of BTK. This cysteine residue is conserved among 9 other tyrosine kinases, including HER2 and EGFR, which can be targeted. Screening large panels of cell lines demonstrated that ibrutinib was growth inhibitory against some solid tumor cells, including those inhibited by other HER2/EGFR inhibitors. Among sensitive cell lines, breast cancer lines with HER2 overexpression were most potently inhibited by ibrutinib (<100 nmol/L); in addition, the IC50s were lower than that of lapatinib and dacomitinib...
December 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27664149/reply-to-the-letter-to-the-editor-possible-determinants-of-vsl-3-probiotic-failure-in-preventing-gastrointestinal-adverse-events-associated-with-dacomitinib-in-patients-with-advanced-non-small-cell-lung-cancer-enrolled-in-archer-1042-trial-by-ceccarelli-et
#16
LETTER
https://www.readbyqxmd.com/read/27517322/therapeutic-implication-of-her2-in-advanced-biliary-tract-cancer
#17
Ah-Rong Nam, Ji-Won Kim, Yongjun Cha, Hyerim Ha, Ji Eun Park, Ju-Hee Bang, Mei Hua Jin, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Do-Youn Oh, Yung-Jue Bang
Currently, there is no validated therapeutic target for biliary tract cancer (BTC). This study aimed to investigate the pre-clinical and clinical implication of HER2 as a therapeutic target in BTC. We established two novel HER2-amplified BTC cell lines, SNU-2670 and SNU-2773, from gallbladder cancer patients. SNU-2670 and SNU-2773 cells were sensitive to trastuzumab, dacomitinib, and afatinib compared with nine HER2-negative BTC cell lines. Dacomitinib and afatinib led to G1 cell cycle arrest in SNU-2773 cells and apoptosis in SNU-2670 cells...
September 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27491023/tyrosine-kinase-inhibitors-20-optimization-of-substituted-quinazoline-and-pyrido-3-4-d-pyrimidine-derivatives-as-orally-active-irreversible-inhibitors-of-the-epidermal-growth-factor-receptor-family
#18
Jeff B Smaill, Andrea J Gonzales, Julie A Spicer, Helen Lee, Jessica E Reed, Karen Sexton, Irene W Althaus, Tong Zhu, Shannon L Black, Adrian Blaser, William A Denny, Paul A Ellis, Stephen Fakhoury, Patricia J Harvey, Ken Hook, Florence O J McCarthy, Brian D Palmer, Freddy Rivault, Kevin Schlosser, Teresa Ellis, Andrew M Thompson, Erin Trachet, R Thomas Winters, Haile Tecle, Alexander Bridges
Structure-activity relationships for inhibition of erbB1, erbB2, and erbB4 were determined for a series of quinazoline- and pyrido[3,4-d]pyrimidine-based analogues of the irreversible pan-erbB inhibitor, canertinib. Cyclic amine bearing crotonamides were determined to provide rapid inhibition of cellular erbB1 autophosphorylation and good metabolic stability in liver microsome and hepatocyte assays. The influence of 4-anilino substitution on pan-erbB inhibitory potency was investigated. Several anilines were identified as providing potent, reversible pan-erbB inhibition...
September 8, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27475932/irreversible-inhibition-of-%C3%AE-16her2-is-necessary-to-suppress-%C3%AE-16her2-positive-breast-carcinomas-resistant-to-lapatinib
#19
Martina Tilio, Valentina Gambini, Junbiao Wang, Chiara Garulli, Cristina Kalogris, Cristina Andreani, Caterina Bartolacci, Maria Elexpuru Zabaleta, Lucia Pietrella, Albana Hysi, Manuela Iezzi, Barbara Belletti, Fiorenza Orlando, Mauro Provinciali, Roberta Galeazzi, Cristina Marchini, Augusto Amici
HER2 tyrosine kinase receptor is a validated target in breast cancer therapy. However, increasing evidence points to a major role of Δ16HER2 splice variant commonly coexpressed with HER2 and identified as a clinically important HER2 molecular alteration promoting aggressive metastatic breast cancer. Consistently, mice transgenic for the human Δ16HER2 isoform (Δ16HER2 mice) develop invasive mammary carcinomas with early onset and 100% penetrance. The present study provides preclinical evidence that Δ16HER2 expression confers de novo resistance to standard anti-HER2-therapies such as Lapatinib and acquired resistance to the selective Src inhibitor Saracatinib in breast cancer...
October 10, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27289242/phase-i-trial-of-dacomitinib-a-pan-human-epidermal-growth-factor-receptor-her-inhibitor-with-concurrent-radiotherapy-and-cisplatin-in-patients-with-locoregionally-advanced-squamous-cell-carcinoma-of-the-head-and-neck-xdc-001
#20
Amy Prawira, Irene Brana-Garcia, Anna Spreafico, Andrew Hope, John Waldron, Albiruni R Abdul Razak, Eric X Chen, Raymond Jang, Brian O'Sullivan, Meredith Giuliani, Andrew Bayley, John Cho, Lisa Wang, Bayardo Perez-Ordonez, Ilan Weinreb, Lillian L Siu, Aaron R Hansen
Background Curative-intent, non-surgical treatment options for locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) include radiotherapy with/without chemotherapy or radiotherapy with cetuximab. This single institution phase I dose escalation trial tested the pan-human epidermal growth factor receptor (HER) oral tyrosine kinase inhibitor, dacomitinib, in combination with standard cisplatin-based chemoradiotherapy. Methods Patients received oral dacomitinib once daily at 3 protocol-defined dose levels (15 mg, 30 mg, and 45 mg)...
October 2016: Investigational New Drugs
keyword
keyword
45666
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"