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Midori Tanaka, Hidenobu Ishii, Hayato Moribuchi, Yoshiko Naito, Norikazu Matsuo, Masayuki Nakamura, Takaaki Tokito, Koichi Azuma, Kazuhiko Yamada, Tomoaki Hoshino
Small-cell lung cancer (SCLC) combined with epidermal growth factor receptor (EGFR) mutations is extremely rare, and standard chemotherapeutic strategies have not yet been established. In the present study, we report a case of a 67-year-old man who presented with combined SCLC with EGFR mutation (exon 19 deletion). Systemic chemotherapy with cisplatin and irinotecan was initiated as first-line chemotherapy, and computed tomography findings revealed tumor shrinkage after two cycles of chemotherapy. However, after the third cycle of the treatment, disease progression was observed including the appearance of pleural and pericardial effusion...
March 15, 2018: Investigational New Drugs
Ramon Andrade De Mello, Carles Escriu, Pedro Castelo-Branco, Paloma Lucena Cabral, Giannis Mountzios, Gilberto de Lima Lopes, Pedro Madureira
Introduction: Tyrosine kinase inhibition of the epidermal growth factor receptor (EGFR) is the standard in the first line treatment of patients with advanced non-small-cell lung cancer (NSCLC) harbouring EGFR activating mutations. Here we aim to discern efficacy and toxicity measures through a meta-analysis of published studies that could aid treatment selection. Materials And Methods: We performed a meta-analysis of the main randomized clinical trials evaluating the currently approved EGFR-TKIs in first-line of treatment of EGFR-positive advanced NSCLC...
February 20, 2018: Oncotarget
Emma D Deeks, Gillian M Keating
Afatinib [Giotrif® (EU); Gilotrif® (USA)] is an orally administered, irreversible inhibitor of the ErbB family of tyrosine kinases that provides an important first-line treatment option for advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations (i.e. EGFRactMUT+ ), and an additional treatment option for squamous NSCLC that has progressed following first-line platinum-based chemotherapy. Relative to gefitinib in the first-line treatment of EGFRactMUT+ advanced lung adenocarcinoma, afatinib prolonged progression-free survival (PFS) and time to treatment failure (TTF), but not overall survival (OS)...
2018: Drugs & Therapy Perspectives: for Rational Drug Selection and Use
Hidejiro Torigoe, Kazuhiko Shien, Tatsuaki Takeda, Takahiro Yoshioka, Kei Namba, Hiroki Sato, Ken Suzawa, Hiromasa Yamamoto, Junichi Soh, Masakiyo Sakaguchi, Shuta Tomida, Kazunori Tsukuda, Shinichiro Miyoshi, Shinichi Toyooka
Human epidermal growth factor receptor 2 (HER2) plays an important role in the pathogenesis of various cancers. HER2 alterations have been suggested to be a therapeutic target in non-small-cell lung cancer (NSCLC), just as in breast and gastric cancers. We previously reported that the pan-HER inhibitor afatinib could be a useful therapeutic agent as HER2-targeted therapy for patients with NSCLC harboring HER2 alterations. However, acquired resistance to afatinib was observed in the clinical setting, similar to the case for other HER inhibitors...
March 13, 2018: Cancer Science
Daisuke Nakamura, Kentaro Miura, Hirotaka Kumeda, Hiroyuki Agatsuma, Akira Hyogotani, Kazutoshi Hamanaka, Tomonobu Koizumi, Hiroshi Yamamoto, Hisashi Tamada, Ken-Ichi Ito
We report a case of pleomorphic carcinoma with exon 18 mutation (G719X) of the epidermal growth factor receptor (EGFR), which showed good response to afatinib and resulted in successful resection. To our knowledge, this is the first report on the use of afatinib for pleomorphic carcinoma followed by the surgical resection. The patient was a 59-year-old woman, who visited our hospital because chest computed tomography showed a 28 × 28-mm nodule in the left upper lobe. Bronchoscopy was performed and the histological findings of transbronchial biopsy revealed adenosquamous carcinoma positive for G719X mutation in exon 18 of the EGFR...
September 2017: Case Reports in Oncology
Hwa Jeong Kang, Ji-Hye Park, Hwa-Seung Yoo, Yu Mi Park, Chong-Kwan Cho, In-Cheol Kang
The present study investigated the toxicity of HangAmDan-B1 (HAD-B1) on A549-Cisplatin resistant (A549CR) cells. HAD‑B1 inhibited the growth of A549CR cells in a concentration‑dependent manner; HAD‑B1 was more effective at inhibiting A549CR cell viability compared with vehicle‑treated cells. The reduction in viability may be due to S‑phase cell cycle arrest and the induction of apoptosis in HAD‑B1‑treated cells. Cell cycle protein profile analysis of HAD‑B1‑treated A549CR cells using an InnoPharmaScreen (IPS) ProteoChip‑based antibody microarray chip indicated downregulation of signal transducer and activator of transcription 3...
March 7, 2018: Molecular Medicine Reports
Raymond Tsz-Tong Chan
Non-small cell lung cancers (NSCLC) harboring the uncommon epidermal growth factor receptor (EGFR) exon 20 insertion mutations are generally thought to be unresponsive to EGFR-tyrosine kinase inhibitor (TKI) therapy. Presented here is a case of stage IV NSCLC harboring an uncommon EGFR exon 20 insertion mutation that was maintained at minimal progressive disease for 54 months, with 36 months on the second-generation TKI afatinib. Contrary to the existing literature, the patient in this case demonstrated a long, durable response to the EGFR-TKI, which was exhibited by a long survival endpoint...
March 2018: Asia-Pacific Journal of Clinical Oncology
Victor H F Lee
A 65-year-old female with diabetes mellitus but otherwise good health in the past suffered from cough with occasional blood-stained sputum during initial presentation. The patient was diagnosed with pulmonary poorly differentiated adenocarcinoma with an epidermal growth factor receptor (EGFR) exon 19 deletion and hence received afatinib therapy for 25 months without obvious adverse events except for a grade 1-2 acneiform rash. The disease was stabilized after subsequent cycles of chemotherapy with pemetrexed and carboplatin followed by maintenance pemetrexed...
March 2018: Asia-Pacific Journal of Clinical Oncology
Nivya James, K Ramanathan
Targeting ErbB family of receptors is an important therapeutic option, because of its essential role in the broad spectrum of human cancers, including non-small cell lung cancer (NSCLC). Therefore, in the present work, considerable effort has been made to develop an inhibitor against HER family proteins, by combining the use of pharmacophore modelling, docking scoring functions, and ADME property analysis. Initially, a five-point pharmacophore model was developed using known HER family inhibitors. The generated model was then used as a query to screen a total of 468,880 compounds of three databases namely ZINC, ASINEX, and DrugBank...
March 6, 2018: Applied Biochemistry and Biotechnology
Shingo Nasu, Hidekazu Suzuki, Takayuki Shiroyama, Ayako Tanaka, Kaori Iwata, Noriko Ryota, Yuki Ueda, S O Takata, Kentaro Masuhiro, Satomu Morita, Naoko Morishita, Norio Okamoto, Tomonori Hirashima
BACKGROUND/AIM: Although afatinib has a strong efficacy, it can be toxic; hence, we aimed to determine markers of response to afatinib in order to assess prognosis. PATIENTS AND METHODS: Information on clinical background, therapeutic effects, and adverse events was collected retrospectively at one Institution from patients treated with afatinib as initial epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI). We examined the relationship between different adverse events and their effects on prognosis...
March 2018: Anticancer Research
Ting-Hui Wu, Emily Han-Chung Hsiue, Jih-Hsiang Lee, Chia-Chi Lin, Wei-Yu Liao, Chao-Chi Ho, Jin-Yuan Shih, Chong-Jen Yu, James Chih-Hsin Yang
INTRODUCTION: The association between the response to first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and survival in EGFR mutation-positive non-small-cell lung cancer (NSCLC) remains unclear. We studied the association between the response to first-line EGFR-TKIs and survival using Response Evaluation Criteria In Solid Tumors (RECIST) and maximal tumor shrinkage. MATERIALS AND METHODS: We analyzed data from patients with advanced EGFR mutation-positive NSCLC enrolled in first-line gefitinib and afatinib trials...
February 1, 2018: Clinical Lung Cancer
Antonin Levy, Corinne Faivre-Finn, Baktiar Hasan, Eleonora De Maio, Anna S Berghoff, Nicolas Girard, Laurent Greillier, Sylvie Lantuéjoul, Mary O'Brien, Martin Reck, Anne-Marie C Dingemans, Silvia Novello, Thierry Berghmans, Benjamin Besse, Lizza Hendriks
BACKGROUND: Brain metastases (BM) are frequent in non-small cell lung cancer (NSCLC) patients, but there is a lack of evidence-based management of this patient group. We aimed to capture a snapshot of routine BM management in Europe to identify relevant research questions for future clinical trials. METHODS: An EORTC Lung Cancer Group (LCG) online survey containing questions on NSCLC BM screening and treatment was distributed between 16/02/17 and 15/06/17 to worldwide EORTC LCG members, and through several European scientific societies in the thoracic oncology field...
February 20, 2018: European Journal of Cancer
Yan Zhang, Changyuan Wang, Zhihao Liu, Qiang Meng, Xiaokui Huo, Qi Liu, Pengyuan Sun, Xiaobo Yang, Huijun Sun, Xiaodong Ma, Kexin Liu
BACKGROUND: Afatinib is an irreversible multi-targeted TKI, used in the treatment with EGFR mutated non-small cell lung cancer (NSCLC). The purpose of this study is to explore the molecular pharmacokinetic mechanism underlying the effect of P-gp inhibitors on the intestinal absorption and biliary excretion and to understand how P-gp inhibitors affect afatinib pharmacokinetics. METHODS: Pharmacokinetics in vivo, in situ intestinal perfusion, perfused rat liver in situ, Caco-2 cells, P-gp ATPase activity, sandwich-cultured rat hepatocytes (SCRH) and transfected-cell transport were used in the evaluation...
November 4, 2017: Pharmacological Reports: PR
Takahiro Yoshioka, Kazuhiko Shien, Kei Namba, Hidejiro Torigoe, Hiroki Sato, Shuta Tomida, Hiromasa Yamamoto, Hiroaki Asano, Junichi Soh, Kazunori Tsukuda, Takeshi Nagasaka, Toshiyoshi Fujiwara, Shinichi Toyooka
Molecularly targeted therapy has enabled outstanding advances in cancer treatment. Whereas various anti-HER2 drugs have been developed, trastuzumab is still the only anti-HER2 drug presently available for gastric cancer. In this study, we propose novel treatment options for patients with HER2-positive gastric cancer. At first, we determined the molecular profiles of 12 gastric cancer cell lines, and examined the antitumor effect of the pan-HER inhibitors afatinib and neratinib in those cell lines. Additionally, we analyzed HER2 alteration in 123 primary gastric cancers resected from Japanese patients to clarify possible candidates with the potential to respond to these drugs...
February 21, 2018: Cancer Science
D Westover, J Zugazagoitia, B C Cho, C M Lovly, L Paz-Ares
Patients with non-small-cell lung cancer (NSCLC) whose tumours harbour activating mutations within the epidermal growth factor receptor (EGFR) frequently derive significant clinical and radiographic benefits from treatment with EGFR tyrosine kinase inhibitors (TKIs). As such, prospective identification of EGFR mutations is now the standard of care worldwide. However, acquired therapeutic resistance to these agents invariably develops. Over the past 10 years, great strides have been made in defining the molecular mechanisms of EGFR TKI resistance in an effort to design rational strategies to overcome this acquired drug resistance...
January 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
W-H Hsu, J C-H Yang, T S Mok, H H Loong
Front-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) therapy is the standard of care for lung cancer patients with sensitising EGFR mutations (exon 19 deletion or L858R mutation). Several phase III studies have demonstrated the superiority of gefitinib, erlotinib (first generation of TKIs) or afatinib (second generation) to chemotherapy in progression-free survival and response rates. Drug-related toxicities, such as diarrhoea, acneiform skin rash, mucositis, and paronychia, are frequently encountered in patients who receive EGFR TKIs...
January 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Shang-Gin Wu, Jin-Yuan Shih
Recent advances in diagnosis and treatment are enabling a more targeted approach to treating lung cancers. Therapy targeting the specific oncogenic driver mutation could inhibit tumor progression and provide a favorable prognosis in clinical practice. Activating mutations of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) are a favorable predictive factor for EGFR tyrosine kinase inhibitors (TKIs) treatment. For lung cancer patients with EGFR-exon 19 deletions or an exon 21 Leu858Arg mutation, the standard first-line treatment is first-generation (gefitinib, erlotinib), or second-generation (afatinib) TKIs...
February 19, 2018: Molecular Cancer
Yuri Taniguchi, Yoko Matsumoto, Ryutaro Furukawa, Sayaka Ohara, Kazuhiro Usui
BACKGROUND: The process of selecting patients on the basis of epidermal growth factor receptor (EGFR) mutations would likely result in a patient population with greater sensitivity to EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, EGFR mutation status is not routinely examined in patients with squamous cell lung cancer (Sq) because of the low incidence of EGFR mutations and the poor clinical response to EGFR-TKIs. METHODS: We retrospectively reviewed the clinical features of patients at our hospital with Sq who carried EGFR-TKI-sensitive EGFR mutations and assessed their responses to EGFR-TKIs...
February 14, 2018: International Journal of Clinical Oncology
Szu-Chun Yang, Chien-Chung Lin, Wu-Wei Lai, Sheng-Mao Chang, Jing-Shiang Hwang, Wu-Chou Su, Jung-Der Wang
Background: Three different tyrosine kinase inhibitors have been approved as first-line therapies for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer with similar overall survival. This study determined dynamic changes in quality of life (QoL) for patients using these therapies after controlling for potential confounders. Methods: From 2011 to 2016, we prospectively assessed the utility values and QoL scores of patients using the EuroQol five-dimension and World Health Organization Quality-of-Life - Brief questionnaires...
2018: Therapeutic Advances in Medical Oncology
Zuhua Chen, Wenwen Huang, Tiantian Tian, Wanchun Zang, Jingyuan Wang, Zhentao Liu, Zhongwu Li, Yumei Lai, Zhi Jiang, Jing Gao, Lin Shen
BACKGROUND: Patient-derived xenograft (PDX) models with definite molecular signature are attractive preclinical models for development of novel targeted drugs. Here, we profiled and explored potential therapeutic targets based on characterized PDX models for advanced gastric cancer (AGC). METHODS: The genomic variation and molecular profile of 50 PDX models from AGC patients were analyzed by targeted next-generation sequencing, in situ hybridization, and immunohistochemistry...
February 13, 2018: Journal of Hematology & Oncology
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