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https://www.readbyqxmd.com/read/28565936/osimertinib-a-third-generation-tyrosine-kinase-inhibitor-for-treatment-of-epidermal-growth-factor-receptor-mutated-non-small-cell-lung-cancer-with-the-acquired-thr790met-mutation
#1
Meredith K Bollinger, Amanda S Agnew, Gerard P Mascara
Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved for the treatment of metastatic EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) in patients failing previous TKI therapy. The T790M mutation is an acquired resistance mechanism found in over half of patients with NSCLC progressing on first-generation TKIs. First- and second-generation TKIs do not inhibit the T790M mutation at clinically relevant concentrations. Osimertinib is selective for mutated forms of EGFR, including the TKI-sensitizing mutations L858R and exon 19 deletions, as well as the acquired T790M resistance mutation...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28469331/differential-toxicities-of-tyrosine-kinase-inhibitors-in-the-management-of-metastatic-lung-cancer
#2
Karthik S Udupa, Rejiv Rajendranath, Tenali Sagar, Joseph Thomas
INTRODUCTION: Erlotinib and gefitinib are the most commonly used epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of EGFR mutant nonsmall cell lung cancer (NSCLC). Both erlotinib and gefitinib have shown equal efficacy in terms of response rates and overall survival. Hence, their toxicity profile becomes the most important determining factor in choosing these agents when treating EGFR mutant NSCLC. In this study, we compared the toxicity profile of erlotinib and gefitinib among an Indian subset of lung cancer patients...
January 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/28464435/management-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-related-cutaneous-and-gastrointestinal-toxicities
#3
REVIEW
Derrick Chen-Wee Aw, Eng Huat Tan, Tan Min Chin, Hong Liang Lim, Haur Yueh Lee, Ross A Soo
Patients with advanced stage non-small cell lung cancer with sensitizing epidermal growth factor receptor (EGFR) mutations using EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib and afatinib as first-line treatment had better progression-free survival, overall response rate and quality of life than those on chemotherapy. Although EGFR TKIs are commonly associated with skin-related (rash, xerosis and paronychia) and gastrointestinal-related (diarrhea and stomatitis) adverse events (AEs), these effects are usually mild...
May 2, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28456787/predictive-blood-plasma-biomarkers-for-egfr-inhibitor-induced-skin-rash
#4
Vivien Hichert, Catharina Scholl, Michael Steffens, Tanusree Paul, Christian Schumann, Stefan Rüdiger, Stefan Boeck, Volker Heinemann, Volker Kächele, Thomas Seufferlein, Julia Stingl
Epidermal growth factor receptor overexpression in human cancer can be effectively targeted by drugs acting as specific inhibitors of the receptor, like erlotinib, gefitinib, cetuximab and panitumumab. A common adverse effect is a typical papulopustular acneiform rash, whose occurrence and severity are positively correlated with overall survival in several cancer types. We studied molecules involved in epidermal growth factor receptor signaling which are quantifiable in plasma, with the aim of identifying biomarkers for the severity of rash...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28442875/extreme-phenotype-of-epidermal-growth-factor-receptor-inhibitor-induced-destructive-folliculitis
#5
Florian Anzengruber, Barbara Meier, Julia-Tatjana Maul, Katrin Kerl, Lars E French, Alexander A Navarini
Due to the increasingly widespread use and side effect profile of epidermal growth factor receptor inhibitors (EGFRIs), cutaneous side effects of these drugs are frequently encountered. The EGFR is expressed on keratinocytes and fibroblasts. Inhibition of EGFR can produce a range of cutaneous adverse effects, the most frequent being a characteristic acneiform skin eruption. As the latter is associated with good anti-neoplastic responses, the onset of EGFRI-induced acneiform skin eruption is typically viewed as a positive sign by patients and physicians...
October 2016: International Journal of Trichology
https://www.readbyqxmd.com/read/28424775/second-line-treatment-of-non-small-cell-lung-cancer-focus-on-the-clinical-development-of-dacomitinib
#6
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/28413391/minocycline-induced-hyperpigmentation-in-a-patient-treated-with-erlotinib-for-non-small-cell-lung-adenocarcinoma
#7
Ann T Bell, John W Roman, Max L Gratrix, Christina E Brzezniak
INTRODUCTION: While epidermal growth factor receptor (EGFR) inhibitors have improved progression-free survival in patients with non-small cell lung cancer (NSCLC), one of the most common adverse effects is papulopustular skin eruption, which is frequently severe enough to be treated with oral minocycline or doxycycline. CASE: We present a case of an 87-year-old man who developed a severe papulopustular skin eruption secondary to erlotinib therapy for NSCLC. Control of the eruption with 100 mg of minocycline twice daily for 8 months eventually led to blue-gray skin hyperpigmentation...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28398611/regulation-of-mir-21-expression-in-human-melanoma-via-uv-ray-induced-melanin-pigmentation
#8
Kuan-Yu Lin, Chien-Min Chen, Cheng-You Lu, Chun-Yuan Cheng, Yu-Hsin Wu
Excessive environmental ultraviolet (UV) radiation produces genetic mutations that can lead to skin cancer. This study was designed to assess the potential inhibitory activity of microRNA-21 (miR-21) on the UV irradiation-stimulated melanogenesis signal pathway in melanoma cells. The molecular mechanism of miR-21-induced inhibitory activity on UV-ray-stimulated melanogenesis-regulating proteins was examined in A375.S2 human melanoma and B16F10 mouse melanoma cells. UV irradiation for 30 min induced melanogenesis signal pathway by increasing melanin production and the number of A375...
April 11, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28390118/erlotinib-associated-rash-in-advanced-non-small-cell-lung-cancer-relation-to-clinicopathological-characteristics-treatment-response-and-survival
#9
Ilias Kainis, Nikolaos Syrigos, Alexandra Kopitopoulou, Ioannis Gkiozos, Effrosyni Filiou, Vasiliki Nikolaou, Evangelia Papadavid
Systematic treatment of advanced Non-Small Cell Lung Cancer (NSCLC) includes targeted treatment with Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs). The development of skin rash and its intensity have been associated with EGFR TKI's efficacy. The main purpose of this study was to further investigate the potential value of Erlotinib - associated rash as a predictor of prognosis and treatment response in a real - world cohort of patients with advanced NSCLC. The medical records of all NSCLC patients, treated with Erlotinib at the Oncology Unit of GPP, Sotiria Athens General Hospital, between 01/01/2014 and 31/08/2016 were retrospectively reviewed...
April 5, 2017: Oncology Research
https://www.readbyqxmd.com/read/28351555/taiwanese-dermatological-association-consensus-for-the-prevention-and-management-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-related-skin-toxicities
#10
Chia-Yu Chu, Kuan-Yu Chen, John Wen-Cheng Chang, Yu-Feng Wei, Chih-Hung Lee, Wei-Ming Wang
BACKGROUND/PURPOSE: This report describes the 2016 consensus of the Taiwanese Dermatological Association (TDA) regarding the definition, classification, diagnosis, prevention, and management of skin toxicities resulting from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). This consensus is distributed to practices throughout Taiwan to provide recommendations for the diagnosis and treatment of such skin toxicities in order to improve the quality of life of patients undergoing EGFR-TKI treatment...
March 27, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28299582/complete-tumor-response-with-afatinib-20%C3%A2-mg-daily-in-egfr-mutated-non-small-cell-lung-cancer-a-case-report
#11
Raffaele Giusti, Marco Mazzotta, Daniela Iacono, Salvatore Lauro, Paolo Marchetti
Afatinib, a second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is efficacious as first-line treatment in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Dosage reduction is recommended in patients with intolerable adverse events; however, data regarding the efficacy of low-dose afatinib are limited. We report the case of a 71-year-old female patient who was diagnosed with advanced EGFR-mutated NSCLC and started treatment with oral afatinib 40 mg daily. The patient achieved partial tumor response on computed tomography imaging, but developed unacceptable skin-related toxicities requiring dosage reduction to 20 mg daily...
June 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28243326/the-research-on-lapatinib-in-autophagy-cell-cycle-arrest-and-epithelial-to-mesenchymal-transition-via-wnt-erk-pi3k-akt-signaling-pathway-in-human-cutaneous-squamous-cell-carcinoma
#12
Ming Yao, Yuan-Yuan Shang, Zhi-Wei Zhou, Yin-Xue Yang, Yin-Sheng Wu, Li-Feng Guan, Xin-Yu Wang, Shu-Feng Zhou, Xi Wei
Cutaneous squamous cell carcinoma (cSCC) contributes to one of most common types of skin cancer. Epidermal growth factor receptor (EGFR) activation has been investigated to be associated with the development of cSCC. Lapatinib is an inhibitor targeting HER2/neu and EGFR pathway. We found that lapatinib can inhibit proliferation by enhancing apoptosis of human cSCC cell lines. The cSCC cell cycle distribution could be arrested in G2/M phase after lapatinib treatment. In the in vitro experiment, we found that lapatinib interrupted PI3K/AKT/mTOR signaling pathway in human cSCC cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28144730/phase-1-study-of-new-formulation-of-patritumab-u3-1287-process-2-a-fully-human-anti-her3-monoclonal-antibody-in-combination-with-erlotinib-in-japanese-patients-with-advanced-non-small-cell-lung-cancer
#13
Toshio Shimizu, Kimio Yonesaka, Hidetoshi Hayashi, Tsutomu Iwasa, Koji Haratani, Hironori Yamada, Shoichi Ohwada, Emi Kamiyama, Kazuhiko Nakagawa
BACKGROUND: This phase 1 study evaluated the safety, tolerability, pharmacokinetics and efficacy of patritumab (U3-1287) Process 2, a new formulation of fully human anti-HER3 monoclonal antibody in combination with erlotinib, an epidermal growth factor receptortyrosine kinase inhibitor (EGFR-TKI) in prior chemotherapy treated Japanese patients with advanced non-small cell lung cancer (NSCLC). METHODS: Patients received intravenous patritumab Process 2 formulation at 9 mg/kg every 3 weeks after initiation of 18 mg/kg loading dose combined with continuous daily dose of erlotinib (150 mg QD) until any of the withdrawal criteria are met...
March 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28123729/randomized-phase-ii-study-of-sequential-carboplatin-plus-paclitaxel-and-gefitinib-in-chemotherapy-na%C3%A3-ve-patients-with-advanced-or-metastatic-non-small-cell-lung-cancer-long-term-follow-up-results
#14
Emi Kubo, Noboru Yamamoto, Hiroshi Nokihara, Yutaka Fujiwara, Hidehito Horinouchi, Shintaro Kanda, Yasushi Goto, Yuichiro Ohe
The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib was initially approved in Japan in 2002 for the treatment of advanced or metastatic non-small-cell lung cancer (NSCLC); however, the optimal order of conventional cytotoxic chemotherapy (carboplatin and paclitaxel) and gefitinib administration has not been determined. We conducted a randomized phase II study of carboplatin and paclitaxel followed by gefitinib vs. gefitinib followed by carboplatin and paclitaxel to select a candidate for further development in a phase III study of chemotherapy-naïve patients with advanced or metastatic NSCLC, regardless of their EGFR mutation status...
January 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28120452/silibinin-treatment-inhibits-the-growth-of-hedgehog-inhibitor-resistant-basal-cell-carcinoma-cells-via-targeting-egfr-mapk-akt-and-hedgehog-signaling
#15
Arpit Dheeraj, Cynthia M Rigby, Cindy L O'Bryant, Chapla Agarwal, Rana P Singh, Gagan Deep, Rajesh Agarwal
Basal cell carcinoma (BCC) is the most common skin malignancy. Deregulated hedgehog signaling plays a central role in BCC development; therefore, hedgehog inhibitors have been approved to treat locally advanced or metastatic BCC. However, the development of resistance to hedgehog inhibitors is the major challenge in effective treatment of this disease. Herein, we evaluated the efficacy of a natural agent silibinin to overcome resistance with hedgehog inhibitors (Sant-1 and GDC-0449) in BCC cells. Silibinin (25-100 μm) treatment for 48 h strongly inhibited growth and induced death in ASZ001, Sant-1-resistant (ASZ001-Sant-1) and GDC-0449-resistant (ASZ001-GDC-0449) BCC cells...
January 25, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28004780/adam17-egfr-axis-promotes-transglutaminase-dependent-skin-barrier-formation-through-phosholipase-c-%C3%AE-1-and-protein-kinase-c-pathways
#16
Cristina Wolf, Yawen Qian, Matthew A Brooke, David P Kelsell, Claus-Werner Franzke
The vitally important skin barrier is formed by extensive cross-linking activity of transglutaminases (TGs) during terminal epidermal differentiation. We have previously shown that epidermal deficiency of a disintegrin and metalloproteinase 17 (ADAM17), the principal EGFR ligand sheddase, results in postnatal skin barrier defects in mice due to impeded TG activity. However, the mechanism by which ADAM17/EGFR signalling maintains TG activity during epidermal differentiation remains elusive. Here we demonstrate that ADAM17-dependent EGFR signalling promotes TG activity in keratinocytes committed to terminal differentiation by direct induction of TG1 expression...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28004308/cutaneous-side-effects-and-transepidermal-water-loss-to-gefitinib-a-study-of-11-patients
#17
Franky Chandra, Dendi Sandiono, Unwati Sugiri, Oki Suwarsa, Hendra Gunawan
INTRODUCTION: Cutaneous side effects caused by epidermal growth factor receptor (EGFR) inhibitors occurred in 45-100% of patients which may lead to therapy modification or interruption. This study aimed to evaluate cutaneous side effects and transepidermal water loss (TEWL) values in non-small cell lung carcinoma (NSCLC) patients who received gefitinib EGFR inhibitor. METHODS: A descriptive observational study with cross-sectional design and a consecutive sampling method was conducted from 1 February to 4 March 2016...
March 2017: Dermatology and Therapy
https://www.readbyqxmd.com/read/27925578/thrombotic-microangiopathy-associated-with-cetuximab-an-epidermal-growth-factor-receptor-inhibitor%C3%A2
#18
Mitsuteru Koizumi, Masahiro Takahashi, Maki Murata, Yuko Kikuchi, Koichi Seta, Kensei Yahata
Cetuximab is a chimeric human-murine monoclonal antibody that binds competitively and with high affinity to the epidermal growth factor receptor (EGFR) and is used to treat advanced squamous cell carcinoma of the head and neck. After receiving a total of six doses of cetuximab, a 72-year-old male presented with pretibial edema, acne-like skin rash, and nephrotic syndrome. The renal biopsy findings revealed features of thrombotic microangiopathy (TMA), with the expansion of the subendothelial zone, reduplication of the glomerular basement, and swelling of the endothelial cells...
January 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/27923840/osimertinib-for-the-treatment-of-metastatic-egfr-t790m-mutation-positive-non-small-cell-lung-cancer
#19
Sean Khozin, Chana Weinstock, Gideon M Blumenthal, Joyce Cheng, Kun He, Luning Zhuang, Hong Zhao, Rosane Charlab, Ingrid Fan, Patricia Keegan, Richard Pazdur
On November 13, 2015, the FDA granted accelerated approval to osimertinib (TAGRISSO; AstraZeneca), a breakthrough therapy-designated drug for the treatment of patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer, as detected by an FDA-approved test, with progression on or after EGFR tyrosine kinase inhibitor therapy. Approval was based on durable tumor response rates in two single-arm, multicenter trials: the dose extension cohort of a first-in-human trial (FIH; AURA extension; n = 201) and a fixed-dose, activity-estimating trial (AURA2; n = 210)...
May 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27912760/update-on-recent-preclinical-and-clinical-studies-of-t790m-mutant-specific-irreversible-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors
#20
REVIEW
Bin-Chi Liao, Chia-Chi Lin, Jih-Hsiang Lee, James Chih-Hsin Yang
The first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (1/2G EGFR-TKIs) gefitinib, erlotinib, and afatinib have all been approved as standard first-line treatments for advanced EGFR mutation-positive non-small cell lung cancer. The third-generation (3G) EGFR-TKIs have been developed to overcome the EGFR T790M mutation, which is the most common mechanism of acquired resistance to 1/2G EGFR-TKI treatment. This resistance mutation develops in half of the patients who respond to 1/2G EGFR-TKI therapy...
December 3, 2016: Journal of Biomedical Science
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