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https://www.readbyqxmd.com/read/28212993/efficacy-according-to-blind-independent-central-review-post-hoc-analyses-from-the-phase-iii-randomized-multicenter-ipass-study-of-first-line-gefitinib-versus-carboplatin-paclitaxel-in-asian-patients-with-egfr-mutation-positive-advanced-nsclc
#1
Yi-Long Wu, Nagahiro Saijo, Sumitra Thongprasert, J C-H Yang, Baohui Han, Benjamin Margono, Busayamas Chewaskulyong, Patrapim Sunpaweravong, Yuichiro Ohe, Yukito Ichinose, Jin-Ji Yang, Tony S K Mok, Helen Young, Vincent Haddad, Yuri Rukazenkov, Masahiro Fukuoka
OBJECTIVE: The Phase III, randomized, open-label IPASS study (NCT00322452) of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) gefitinib versus carboplatin/paclitaxel for Asian patients with advanced non-small-cell lung cancer (NSCLC) showed that investigator-assessed progression-free survival (PFS) and objective response rate (ORR) were significantly prolonged in patients with EGFR mutation-positive NSCLC who received gefitinib versus patients with EGFR mutation-negative NSCLC...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28210267/mir-30-family-potentially-targeting-pi3k-siah2-predicted-interaction-network-represents-a-novel-putative-theranostic-panel-in-non-small-cell-lung-cancer
#2
Lawrence W C Chan, Fengfeng Wang, Fei Meng, Lili Wang, Sze Chuen Cesar Wong, Joseph S K Au, Sijun Yang, William C S Cho
Non-small cell lung cancer (NSCLC) comprises about 84% of all lung cancers. Many treatment options are available but the survival rate is still very low due to drug resistance. It has been found that phosphoinositide-3-kinase (PI3K) affects sensitivity to tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib. Expression level of seven in absentia homolog 2 (SIAH2), an E3 ubiquitin-protein ligase, is upregulated in NSCLC and correlated with tumor grade. However, the relationship between PI3K and SIAH2 remains unclear and therefore it is not known whether they can act as treatment co-targets and theranostic dual markers for overcoming TKI resistance...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28193529/heterogeneity-in-immune-marker-expression-after-acquisition-of-resistance-to-egfr-kinase-inhibitors-analysis-of-a-case-with-small-cell-lung-cancer-transformation
#3
Kenichi Suda, Isao Murakami, Hui Yu, Jihye Kim, Kim Ellison, Christopher J Rivard, Tetsuya Mitsudomi, Fred R Hirsch
INTRODUCTION: Expression of immune-markers is of scientific interest due to their potential roles as predictive biomarkers for immunotherapy. Although the microenvironment of metastatic tumors and/or therapy-inducible histological transformation may affect the expression of these immune-markers, there is little data regarding this context. METHODS: A 76-year-old never-smoking female with epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma (AC) acquired resistance to gefitinib...
February 10, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28191799/switch-maintenance-tyrosine-kinase-inhibitors-in-egfr-mutation-positive-metastatic-non-squamous-nsclc-experience-from-the-real-world
#4
Ayinash Pandey, V Noronha, A Joshi, K Prabhash
BACKGROUND: Induction pemetrexed platin doublet is the standard of care in locally advanced and metastatic non squamous NSCLC. Maintenance TKI has been successfully explored to sustain benefit achieved after induction therapy especially in EGFR mutation positive NSCLC. The aim of this study is to evaluate outcomes with maintenance TKI in EGFR mutation positive metastatic non squamous NSCLC after induction pemetrexed-platin doublet. The objective is to calculate progression freesurvival rate, overall survival rate and factors affecting outcomes...
September 2016: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/28190599/retrospective-analysis-of-different-treatment-schemes-after-gefitinib-resistance-in-advanced-non-small-cell-lung-cancer
#5
Huijuan Wang, Mina Zhang, Peng Li, Guowei Zhang, Xiangtao Yan, Zhiyong Ma
PURPOSE: The goal of this study was to assess the survival of patients with acquired resistance to gefitinib who underwent different subsequent treatments. METHODS: From September 2007 to July 2014, a total of 103 patients with pathologically confirmed advanced non-small cell lung cancer and acquired resistance to gefitinib were retrospectively analyzed. Fifty-eight (56%) patients received chemotherapy; 36 were treated with chemotherapy and gefitinib continuation (CT + G), and 22 patients received chemotherapy (CT) alone...
February 9, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28188446/treatment-options-for-egfr-t790m-negative-egfr-tyrosine-kinase-inhibitor-resistant-non-small-cell-lung-cancer
#6
Salvatore Corallo, Ettore D'Argento, Antonia Strippoli, Michele Basso, Santa Monterisi, Sabrina Rossi, Alessandra Cassano, Carlo M Barone
The introduction of first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) (gefitinib, erlotinib and afatinib) for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC) has dramatically improved patients' prognosis and quality of life (QoL). Unfortunately, after an initial and sometimes durable benefit from EGFR-TKI therapy, all patients with EGFR-mutant lung cancer eventually become resistant to the treatment and experience disease progression. In approximately 50% of these patients, genomic alterations in the EGFR kinase domain resulting in the mutant T790M are responsible for the resistance and this has led to the development of novel EGFR inhibitors active against mutant-T790M EGFR...
February 10, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28181105/protein-kinase-ck2-is-important-for-the-function-of-glioblastoma-brain-tumor-initiating-cells
#7
Amber L Rowse, Sara A Gibson, Gordon P Meares, Rajani Rajbhandari, Susan E Nozell, Kory J Dees, Anita B Hjelmeland, Braden C McFarland, Etty N Benveniste
Protein kinase CK2 is a ubiquitously expressed serine/threonine kinase composed of two catalytic subunits (α) and/or (α') and two regulatory (β) subunits. The expression and kinase activity of CK2 is elevated in many different cancers, including glioblastoma (GBM). Brain tumor initiating cells (BTICs) are a subset of cells that are highly tumorigenic and promote the resistance of GBM to current therapies. We previously reported that CK2 activity promotes prosurvival signaling in GBM. In this study, the role of CK2 signaling in BTIC function was examined...
February 8, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28179132/gefitinib-gefitinib-microspheres-loaded-polyurethane-constructs-as-drug-eluting-stent-coating
#8
Weiluan Chen, Johanna Clauser, Anja Lena Thiebes, Donnacha J McGrath, Nicola Kelly, Mies J van Steenbergen, Stefan Jockenhoevel, Ulrich Steinseifer, Peter E McHugh, Wim E Hennink, Robbert J Kok
One of the complications of bronchotracheal cancer is obstruction of the upper airways. Local tumor resection in combination with an airway stent can suppress intraluminal tumor (re)growth. We have investigated a novel drug-eluting stent coating for local release of the anticancer drug gefitinib. A polyurethane (PU) sandwich construct was prepared by a spray coating method in which gefitinib was embedded between a PU support layer of 200μm and a PU top layer of 50-200μm. Gefitinib was either embedded in the construct as small crystals or as gefitinib-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MSP)...
February 4, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28178657/liver-x-receptors-agonist-gw3965-re-sensitizes-gefitinib-resistant-human-non-small-cell-lung-cancer-cell-to-gefitinib-treatment-by-inhibiting-nf-%C3%AE%C2%BAb-in-vitro
#9
Yong Hu, Jialan Zang, Haixia Cao, Ying Wu, Dali Yan, Xiaobing Qin, Leilei Zhou, Fan Fan, Jie Ni, Xiaoyue Xu, Huanhuan Sha, Siwen Liu, Shaorong Yu, Zhuo Wang, Rong Ma, Jianzhong Wu, Jifeng Feng
The recent research shows that the inhibition of the nuclear factor-κB (NF-κB) pathway is a promising therapeutic option for patients who progress after treatment with the novel mutant-selective EGFR-TKIs. For propose to find a nontoxic drug to reverse the acquired gefitinib resistance, we examined whether the Liver X Receptors agonist GW3965 affect gefitinib resistance of HCC827/GR-8-2 cells. Cell viability was measured by CCK-8 assay. Levels of NF-κB, p-AKT and caspases were detected by Western blot analysis...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28176470/effect-of-sustained-elevated-gastric-ph-levels-on-gefitinib-exposure
#10
Weifeng Tang, Helen Tomkinson, Eric Masson
This open-label, randomized, phase 1 crossover study investigated the effect of elevated gastric pH level (>5) on the relative bioavailability and pharmacokinetic profile of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib. Healthy male volunteers (n = 26) were randomized to gefitinib 250 mg (fasted), either alone on day 1 (unmodified gastric pH) or 1 hour following the second of 2 oral doses of the H2 -receptor antagonist ranitidine 450 mg (elevated gastric pH). After a 3-week washout period, volunteers crossed to the other treatment...
February 8, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28169392/afatinib-versus-gefitinib-in-patients-with-egfr-mutation-positive-advanced-non-small-cell-lung-cancer-overall-survival-data-from-the-phase-iib-lux-lung-7-trial
#11
L Paz-Ares, E-H Tan, K O'Byrne, L Zhang, V Hirsh, M Boyer, J C-H Yang, T Mok, K H Lee, S Lu, Y Shi, D H Lee, J Laskin, D-W Kim, S A Laurie, K Kölbeck, J Fan, N Dodd, A Märten, K Park
No abstract text is available yet for this article.
February 7, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28168310/evaluation-of-gefitinib-efficacy-according-to-body-mass-index-body-surface-area-and-body-weight-in-patients-with-egfr-mutated-advanced-non-small-cell-lung-cancer
#12
Hisao Imai, Tomohito Kuwako, Kyoichi Kaira, Tomomi Masuda, Yosuke Miura, Kaori Seki, Reiko Sakurai, Mitsuyoshi Utsugi, Kimihiro Shimizu, Noriaki Sunaga, Yoshio Tomizawa, Shinichi Ishihara, Takao Ishizuka, Akira Mogi, Takeshi Hisada, Koichi Minato, Atsushi Takise, Ryusei Saito, Masanobu Yamada
PURPOSE: In patients with epidermal growth factor receptor (EGFR)-mutated, advanced, non-small cell lung cancer (NSCLC), common gefitinib-sensitive EGFR mutations that predict a greater response to therapy include the exon 19 deletion and L858R point mutation. The objective of this study was to evaluate whether body surface area (BSA), body weight (BW), and body mass index (BMI) affect gefitinib efficacy in such patients. METHODS: The medical charts of 138 consecutive patients with advanced NSCLC harboring sensitive EGFR mutations, who underwent gefitinib treatment, were reviewed...
February 6, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28167215/treatments-for-egfr-mutant-non-small-cell-lung-cancer-nsclc-the-road-to-a-success-paved-with-failures
#13
REVIEW
Dae Ho Lee
The discovery of epidermal growth factor receptor (EGFR) activating mutations in non-small cell lung cancer (NSCLC) and the success story of EGFR tyrosine kinases inhibitors (TKIs) has changed the paradigm of cancer therapy from empirical cytotoxic chemotherapy to molecular-targeted cancer therapy. As a result, EGFR TKI therapy, including gefitinib, erlotinib and afatinib, has become the standard therapy for NSCLC patients with EGFR activating mutation as first-line therapy. However, most patients inevitably progress despite initial dramatic and rapid response to EGFR TKIs and therefore during the last decade, a lot of efforts have been made to identify and overcome various resistance mechanisms...
February 3, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28165895/gefitinib-or-erlotinib-for-previously-treated-lung-adenocarcinoma-which-is-superior
#14
Chia-Hao Chang, Chih-Hsin Lee, Jann-Yuan Wang
No abstract text is available yet for this article.
February 6, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28165387/concurrent-autophagy-inhibition-overcomes-the-resistance-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-in-human-bladder-cancer-cells
#15
Minyong Kang, Kyoung-Hwa Lee, Hye Sun Lee, Chang Wook Jeong, Cheol Kwak, Hyeon Hoe Kim, Ja Hyeon Ku
Despite the potential therapeutic efficacy of epithelial growth factor receptor (EGFR) inhibitors in the treatment of advanced stage bladder cancer, there currently is no clear evidence to support this hypothesis. In this study, we investigate whether the concurrent treatment of autophagy-blocking agents with EGFR inhibitors exerts synergistic anti-cancer effects in T24 and J82 human bladder cancer cells. Lapatinib and gefitinib were used as EGFR inhibitors, and bafilomycin A1 (BFA1), chloroquine (CQ) and 3-methyladenine (3-MA) were used as the pharmacologic inhibitors of autophagy activities...
February 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28164096/gefitinib-with-pemetrexed-as-first-line-therapy-in-patients-with-advanced-nonsquamous-non-small-cell-lung-cancer-with-activating-epidermal-growth-factor-receptor-mutations
#16
EDITORIAL
Shinkyo Yoon, Dae Ho Lee, Sang-We Kim
No abstract text is available yet for this article.
January 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28162944/epidermal-growth-factor-receptor-egfr-mutation-in-exon-19-p-e749q-confers-resistance-to-gefitinib-in-one-patient-with-lung-adenocarcinoma
#17
Giovenzio Genestreti, Dario de Biase, Monica Di Battista, Giovanna Cavallo, Roberta Degli Esposti, Michela Visani, Giorgia Acquaviva, Thomas Brand, Annalisa Pession, Giovanni Tallini, Alba A Brandes
No abstract text is available yet for this article.
January 11, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28153500/endothelin-causes-transactivation-of-the-egfr-and-her2-in-non-small-cell-lung-cancer-cells
#18
Terry W Moody, Irene Ramos-Alvarez, Paola Moreno Perez, Samuel A Mantey, Lisa Ridnour, David Wink, Robert T Jensen
Endothelin (ET)-1 is an important peptide in cancer progression stimulating cellular proliferation, tumor angiogenesis and metastasis. ET-1 binds with high affinity to the ETA receptor (R) and ETBR on cancer cells. High levels of tumor ET-1 and ETAR are associated with poor survival of lung cancer patients. Here the effects of ET-1 on epidermal growth factor (EGF)R and HER2 transactivation were investigated using non-small cell lung cancer (NSCLC) cells. ETAR mRNA was present in all 10 NSCLC cell lines examined...
January 30, 2017: Peptides
https://www.readbyqxmd.com/read/28152323/chemotherapy-and-intercalated-gefitinib-or-erlotinib-in-the-treatment-of-advanced-non-small-cell-lung-cancer
#19
Antonio Rossi, Anna La Salvia, Massimo Di Maio
Preclinical data showed that intercalated administration of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy might be effective in the treatment of advanced non-small-cell lung cancer (NSCLC). This review will summarize and discuss the clinical results available to date from prospective studies investigating this approach. Areas covered: A structured search of bibliographic databases for peer-reviewed literature and of main International meetings was undertaken, for trials testing the intercalated addition of EGFR-TKIs to chemotherapy in advanced NSCLC...
February 2, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28149764/third-generation-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-in-t790m-positive-non-small-cell-lung-cancer-review-on-emerged-mechanisms-of-resistance
#20
REVIEW
Roberta Minari, Paola Bordi, Marcello Tiseo
Osimertinib, third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been approved in the US and EU for the treatment of EGFR mutant T790M-positive non-small cell lung cancer (NSCLC) patients resistant to first- or second-generation EGFR-TKIs, such as gefitinib, erlotinib and afatinib. Although exciting survival data and response rates have been registered in patients treated with this and other third-generation EGFR-TKIs, unfortunately acquired resistance still occurs after approximately 10 months...
December 2016: Translational Lung Cancer Research
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