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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
#1
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...
January 31, 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
#2
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
#3
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 hrs 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
#4
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
#5
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...
December 21, 2016: Dermatology and Therapy
https://www.readbyqxmd.com/read/27925578/thrombotic-microangiopathy-associated-with-cetuximab-an-epidermal-growth-factor-receptor-inhibitor%C3%A2
#6
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-epidermal-growth-factor-t970m-positive-non-small-cell-lung-cancer
#7
Sean Khozin, Chana Weinstock, Gideon M Blumenthal, Joyce Cheng, Kun He, Luning Zhuang, Hong Zhao, Rosane Charlab Orbach, Ingrid Fan, Patricia Keegan, Richard Pazdur
On November 13, 2015, FDA granted accelerated approval to osimertinib (TAGRISSO™; AstraZeneca), a breakthrough therapy-designated drug for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC), 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 (AURA extension; n=201) and a fixed-dose, activity-estimating trial (AURA2; n=210)...
December 6, 2016: 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
#8
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
https://www.readbyqxmd.com/read/27893423/efficacy-and-safety-of-icotinib-in-treating-non-small-cell-lung-cancer-a-systematic-evaluation-and-meta-analysis-based-on-15-studies
#9
Rong Biaoxue, Liu Hua, Gao Wenlong, Yang Shuanying
Icotinib is a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that developed and used in China; this work was to evaluate its efficacy and safety in treating non-small cell lung cancer (NSCLC). Clinical studies evaluating the efficacy and safety of icotinib in treating NSCLC were identified from the databases of Medline, Web of Science, Embase and Cochrance Library. Pooled efficacy and safety of icotinib were calculated through a series of predefined search strategies. A total of 15 studies with 2,304 patients were involved in this study...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27836854/a-novel-spectroscopically-determined-pharmacodynamic-biomarker-for-skin-toxicity-in-cancer-patients-treated-with-targeted-agents
#10
Antoine Azan, Peter J Caspers, Tom C Bakker Schut, Séverine Roy, Céline Boutros, Christine Mateus, Emilie Routier, Benjamin Besse, David Planchard, Atmane Seck, Nyam Kamsu Kom, Gorana Tomasic, Senada Koljenović, Vincent Noordhoek Hegt, Matthieu Texier, Emilie Lanoy, Alexander M M Eggermont, Angelo Paci, Caroline Robert, Gerwin J Puppels, Lluis M Mir
Raman spectroscopy is a noninvasive and label-free optical technique that provides detailed information about the molecular composition of a sample. In this study, we evaluated the potential of Raman spectroscopy to predict skin toxicity due to tyrosine kinase inhibitors treatment. We acquired Raman spectra of skin of patients undergoing treatment with MEK, EGFR, or BRAF inhibitors, which are known to induce severe skin toxicity; for this pilot study, three patients were included for each inhibitor. Our algorithm, based on partial least squares-discriminant analysis (PLS-DA) and cross-validation by bootstrapping, discriminated to variable degrees spectra from patient suffering and not suffering cutaneous adverse events...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/27833902/minocycline-improves-the-efficacy-of-egfr-inhibitor-therapy-a-hypothesis
#11
Ajit Venniyoor, Bassim Al Bahrani
Skin rash is a side effect of drugs that inhibit epithelial growth factor receptor (EGFR) as a part of targeted therapy of cancer. Its appearance and severity correlates with survival. Minocycline, an oral tetracycline antibiotic, is recommended as treatment (and increasingly, for prevention) of the rash, though infection is seen in only one-third of the patients. Minocycline has additional anticancer properties such as poly(ADP-ribose) polymerase inhibition. It is proposed that such properties contribute to the efficacy of EGFR inhibitors and can also explain the positive correlation between grade of rash and survival as patients with higher grades of rash are more likely to receive minocycline...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27825616/vandetanib-in-patients-with-previously-treated-ret-rearranged-advanced-non-small-cell-lung-cancer-luret-an-open-label-multicentre-phase-2-trial
#12
Kiyotaka Yoh, Takashi Seto, Miyako Satouchi, Makoto Nishio, Noboru Yamamoto, Haruyasu Murakami, Naoyuki Nogami, Shingo Matsumoto, Takashi Kohno, Koji Tsuta, Katsuya Tsuchihara, Genichiro Ishii, Shogo Nomura, Akihiro Sato, Atsushi Ohtsu, Yuichiro Ohe, Koichi Goto
BACKGROUND: RET rearrangements are rare oncogenic alterations in non-small-cell lung cancer (NSCLC). Vandetanib is a multitargeted tyrosine kinase inhibitor exhibiting RET kinase activity. We aimed to assess the efficacy and safety of vandetanib in patients with advanced RET-rearranged NSCLC. METHODS: In this open-label, multicentre, phase 2 trial (LURET), patients with advanced RET-rearranged NSCLC continuously received 300 mg of oral vandetanib daily. RET-positive patients were screened using a nationwide genomic screening network of about 200 participating institutions...
January 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/27791234/cutaneous-toxicity-from-epidermal-growth-factor-receptor-inhibitors-would-a-subcutaneous-desensitization-be-helpful-case-report
#13
Andrea D'Alessio, Sara Cecchini, Daniela Di Mauro, Luca Geroli, Simonetta Villa, Antonello Quadri, Davide Resta, Carmelo Fortugno
PURPOSE: Cetuximab and panitumumab are monoclonal antibody inhibitors that bind the epidermal growth factor receptor (EGFR) currently used in the treatment of metastatic colorectal cancer. The main adverse event related to EGFR inhibitors (EGFR-Is) is cutaneous toxicity, which can cause dosage reduction and interruption of treatment. State-of-the-art management of skin toxicity associated with EGFR-Is therapy involves the topical administration of corticosteroids and oral antibiotics, but is not completely effective in the management of toxicity...
November 11, 2016: Tumori
https://www.readbyqxmd.com/read/27766784/retrospective-study-of-adjuvant-icotinib-in-postoperative-lung-cancer-patients-harboring-epidermal-growth-factor-receptor-mutations
#14
Shuyang Yao, Xiuyi Zhi, Ruotian Wang, Kun Qian, Mu Hu, Yi Zhang
BACKGROUND: Epidermal growth factor receptor (EGFR) mutations occur in about 50% of Asian patients with non-small cell lung cancer (NSCLC). Patients with advanced NSCLC and EGFR mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors (TKIs). This study assessed the efficacy and safety of adjuvant icotinib without chemotherapy in EGFR-mutated NSCLC patients undergoing resection of stage IB-IIIA. METHODS: Our retrospective study enrolled 20 patients treated with icotinib as adjuvant therapy...
September 2016: Thoracic Cancer
https://www.readbyqxmd.com/read/27755795/lung-squamous-cell-carcinoma-with-brachial-soft-tissue-metastasis-responsive-to-gefitinib-report-of-a-rare-case
#15
Kana Kataoka, Eiji Osaka, Tetsuo Shimizu, Yuki Okamura, Yukihiro Yoshida, Yasuaki Tokuhashi
Metastasis of lung cancer to soft tissue is rare and patient outcomes are generally poor. There are no reports describing soft tissue metastasis in lung squamous cell carcinoma (SCC), in which gefitinib treatment was effective not only for the primary tumor but also the metastatic lesion. A 61-year-old Asian woman presented to our facility with pain and a mass in the brachium. An additional tumor was identified in the lung. As we suspected soft tissue metastasis of lung cancer, an incisional biopsy was performed, yielding a diagnosis of SCC...
November 2016: Thoracic Cancer
https://www.readbyqxmd.com/read/27725919/afatinib-associated-cutaneous-toxicity-a-correlation-of-severe-skin-reaction-with-dramatic-tumor-response-in-a-woman-with-exon-19-deletion-positive-non-small-cell-lung-cancer
#16
Lindsay P Osborn, Philip R Cohen
Epidermal growth factor receptor (EGFR) inhibitors are biological factors used in the treatment of non-small-cell lung cancers (NSCLC) that are positive for EGFR mutations. Afatinib is one such drug that has been approved for use in this capacity. Cutaneous toxicity is the second most commonly reported adverse event with the use of afatinib. A 39-year-old woman with inoperative right lung adenocarcinoma was initially treated with afatinib. She not only developed a severe papulopustular eruption but also had a dramatic reduction of her tumor...
September 1, 2016: Curēus
https://www.readbyqxmd.com/read/27720938/identification-of-gene-expression-profiling-associated-with-erlotinib-related-skin-toxicity-in-pancreatic-adenocarcinoma-patients
#17
Octavio Caba, Antonio Irigoyen, Cristina Jimenez-Luna, Manuel Benavides, Francisco M Ortuño, Javier Gallego, Ignacio Rojas, Carmen Guillen-Ponce, Carolina Torres, Enrique Aranda, Jose Prados
Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that showed activity against pancreatic ductal adenocarcinoma (PDAC). The drug's most frequently reported side effect as a result of EGFR inhibition is skin rash (SR), a symptom which has been associated with a better therapeutic response to the drug. Gene expression profiling can be used as a tool to predict which patients will develop this important cutaneous manifestation. The aim of the present study was to identify which genes may influence the appearance of SR in PDAC patients...
October 6, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27718067/dermatologic-events-from-egfr-inhibitors-the-issue-of-the-missing-patient-voice
#18
REVIEW
Bernd Tischer, Renate Huber, Matthias Kraemer, Mario E Lacouture
PURPOSE: As epidermal growth factor receptor (EGFR) inhibitors are associated with a variety of dermatologic adverse events (dAEs), the purpose of this study was to develop an overview of current knowledge of dAEs associated with EGFR inhibitors and to identify knowledge gaps regarding incidence, treatment, impact on quality of life (QOL), and patient acceptance. METHOD: A structured literature search was conducted using MEDLINE/PubMed (January 1983 to January 2014)...
February 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/27680009/-cutaneous-squamous-cell-carcinoma
#19
REVIEW
U Leiter, R Gutzmer, M Alter, C Ulrich, A S Lonsdorf, M M Sachse, U Hillen
Squamous cell carcinoma (SCC) of the skin accounts for 20 % of non-melanoma skin cancer and is one of the most frequent types of cancer in Caucasian populations. Diagnosis is based on the clinical features and should be histopathologically confirmed to adequately address the prognosis and treatment. Complete surgical excision with histopathological control of excision margins is the gold standard in the treatment of primary SCC. Sentinel lymph node biopsies (SLNB) can be considered in SCC with a tumor thickness of >6 mm but there is currently no evidence concerning prognostic and therapeutic effects...
November 2016: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/27668532/anti-proliferation-effects-efficacy-of-cyasterone-in-vitro-and-in-vivo-and-its-mechanism
#20
XinGang Lu, HongFu Qiu, Liu Yang, JieYing Zhang, ShuJie Ma, Lan Zhen
Cyasterone was demonstrated potential inhibition effect in mouse skin carcinoma cells in published report. However, the molecular mechanisms of the cyasterone on cells remain unknown. Herein, we investigated the effects of cyasterone-induced apoptosis in A549 and MGC823 cells in vitro. MTT assay showed that cyasterone caused a significantly decreasing of the proliferation of A549 and MGC823 cells in a time-and dose-dependent manner with IC50 values of 38.50±3.73μg/mL on A549 cells and 32.96±1.24μg/mL on MGC823 cells at 48h, respectively...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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