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Crizotinib

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https://www.readbyqxmd.com/read/28731868/inflammatory-myofibroblastic-tumors-of-the-female-genital-tract-are-under-recognized-a-low-threshold-for-alk-immunohistochemistry-is-required
#1
Justine L Pickett, Angela Chou, Juliana A Andrici, Adele Clarkson, Loretta Sioson, Amy Sheen, Jessica Reagh, Fedaa Najdawi, Yoomee Kim, Denise Riley, Jayne Maidens, David Nevell, Kirsten McIlroy, Susan Valmadre, Greg Gard, Russell Hogg, John Turchini, Gregory Robertson, Michael Friedlander, Anthony J Gill
Inflammatory myofibroblastic tumor (IMT) of the female genital tract is under-recognized. We investigated the prevalence of ALK-positive IMT in lesions previously diagnosed as gynecologic smooth muscle tumors. Immunohistochemistry (IHC) for ALK was performed on tissue microarrays of unselected tumors resected from 2009 to 2013. Three of 1176 (0.26%) "leiomyomas" and 1 of 44 (2.3%) "leiomyosarcomas" were ALK IHC positive, confirmed translocated by fluorescence in situ hybridization (FISH) and therefore more appropriately classified as IMT...
July 20, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28730760/targeted-therapy-with-anaplastic-lymphoma-kinase-inhibitors-in-non-small-cell-lung-cancer-even-with-brain-metastasis
#2
Bekir Muhammet Hacioglu, Osman Kostek, Bulent Erdogan, Sernaz Uzunoglu, Irfan Cicin
The incidence of brain metastases has increased as a result of improved systemic disease control and advances in imaging. Brain metastasis can occur approximately in 25-40% of the patients with non-small cell lung cancer (NSCLC) and it is a frequent cause of death. Stereotactic radiosurgery, whole-brain radiotherapy (WBRT) or surgical resection are the local treatment modalities for brain metastases which are feasible either alone, in combination, or as sequential treatments. Resistance to systemic therapy for brain metastasis poses significant clinical problems...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28729021/ascend-8-a-randomized-phase-1-study-of-ceritinib-450-mg-or-600-mg-taken-with-a-low-fat-meal-versus-750-mg-in-fasted-state-in-patients-with-anaplastic-lymphoma-kinase-alk-rearranged-metastatic-non-small-cell-lung-cancer-nsclc
#3
Byoung Chul Cho, Dong-Wan Kim, Alessandra Bearz, Scott A Laurie, Mark McKeage, Gloria Borra, Keunchil Park, Sang-We Kim, Marwan Ghosn, Andrea Ardizzoni, Evaristo Maiello, Alastair Greystoke, Richard Yu, Karen Osborne, Wen Gu, Jeffrey W Scott, Vanessa Q Passos, Yvonne Y Lau, Anna Wrona
INTRODUCTION: Ceritinib 750 mg fasted is approved for treatment of anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) patients previously treated with crizotinib. Part 1 of ASCEND-8 study determined whether administering ceritinib 450 mg or 600 mg with a low-fat meal may enhance gastrointestinal (GI) tolerability vs 750 mg fasted in ALK+ NSCLC patients while maintaining similar exposure. METHODS: ASCEND-8 is a multicenter, randomized, open-label, phase 1 study...
July 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28721071/adverse-renal-effects-of-anaplastic-lymphoma-kinase-inhibitors-and-the-response-to-alectinib-of-an-alk-lung-cancer-patient-with-renal-dysfunction
#4
Midori Shimada, Minoru Fukuda, Masaaki Fukuda, Takeshi Kitazaki, Kohji Hashiguchi, Takaya Ikeda, Hiroyuki Yamaguchi, Katsumi Nakatomi, Kazuto Ashizawa, Hiroshi Mukae
A 62-year-old female patient with renal dysfunction and pulmonary adenocarcinoma developed postoperative recurrence and received carboplatin/pemetrexed and maintenance pemetrexed. As an anaplastic lymphoma kinase (ALK) gene translocation was identified, the therapy was changed to crizotinib. However, the patient's blood creatinine level increased, and her physical status worsened. Alectinib also induced exacerbation of renal dysfunction but was controlled by dose reduction of 140 mg twice daily for 2 weeks treatment and 2 weeks break were repeated, and exhibited a partial response for 16 months...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28721068/patients-harboring-alk-rearrangement-adenocarcinoma-after-acquired-resistance-to-crizotinib-and-transformation-to-small-cell-lung-cancer-a-case-report
#5
You-Cai Zhu, Xing-Hui Liao, Wen-Xian Wang, Chun-Wei Xu, Wu Zhuang, Li-Hua Zhong, Kai-Qi Du, Yan-Ping Chen, Gang Chen, Mei-Yu Fang
Anaplastic lymphoma kinase (ALK) rearrangement responds to ALK tyrosine kinase inhibitors (TKIs) in lung cancer. Many cases ultimately acquire resistance to crizotinib. Resistance, including ALK-dominant or ALK non-dominant, mechanisms have been described. Transformation to small-cell lung cancer is rare. Herein, we report a 49-year-old man diagnosed with adenocarcinoma, who was negative for EGFR and ALK genes as detected by reverse transcription polymerase chain reaction, and was treated with crizotinib. A new biopsy showed a small-cell lung cancer after disease progression...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28717217/tki-addicted-ros1-rearranged-cells-are-destined-to-survival-or-death-by-the-intensity-of-ros1-kinase-activity
#6
Hayato Ogura, Yuka Nagatake-Kobayashi, Jun Adachi, Takeshi Tomonaga, Naoya Fujita, Ryohei Katayama
ROS1 rearrangement is observed in 1-2% of non-small cell lung cancers (NSCLC). The ROS1 tyrosine kinase inhibitor (TKI) crizotinib has induced marked tumour shrinkage in ROS1-rearranged cancers. However, emergence of acquired resistance to TKI is inevitable within a few years. Previous findings indicate that cabozantinib overcomes secondary mutation-mediated crizotinib-resistance in ROS1-fusion-positive cells. Here we attempted to establish cabozantinib-resistant cells by N-ethyl-N-nitrosourea mutagenesis screening using CD74-ROS1-expressing Ba/F3 cells...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28705139/anaplastic-lymphoma-kinase-alk-mutations-in-patients-with-adenocarcinoma-of-the-lung
#7
N Mohamad, P Jayalakshmi, A Rhodes, C-K Liam, J-L Tan, S Yousoof, P Rajadurai
BACKGROUND: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death. Approximately 2-16% of NSCLC patients with wild-type epidermal growth factor receptor (EGFR) harbour anaplastic lymphoma kinase (ALK) mutations. Both EGFR and ALK mutations occur most commonly in Asian patients with NSCLC. As targeted therapy is available for NSCLC patients with these mutations, it is important to establish reliable assays and testing strategies to identify those most likely to benefit from this therapy...
July 13, 2017: British Journal of Biomedical Science
https://www.readbyqxmd.com/read/28702420/complete-response-with-crizotinib-in-two-children-with-chemotherapy-resistant-neuroblastoma
#8
Priyanka Verma, Sandeep Jain, Gauri Kapoor
No abstract text is available yet for this article.
April 2017: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/28701030/crizotinib-versus-chemotherapy-in-asian-patients-with-advanced-alk-positive-non-small-cell-lung-cancer
#9
Makoto Nishio, Dong-Wan Kim, Yi-Long Wu, Kazuhiko Nakagawa, Benjamin J Solomon, Alice T Shaw, Satoshi Hashigaki, Emiko Ohki, Tiziana Usari, Jolanda Paolini, Anna Polli, Keith D Wilner, Tony Mok
Purpose: Crizotinib has demonstrated superior progression-free survival (PFS) and objective response rates (ORRs) versus chemotherapy in previously treated and untreated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). We report the safety and efficacy of crizotinib in Asian subpopulations of two global phase III trials. Materials and Methods: This analysis evaluated previously treated and untreated patients in two randomized, open-label phase III trials of crizotinib versus chemotherapy in ALK-positive advanced NSCLC in second-line (PROFILE 1007) and first-line settings (PROFILE 1014)...
July 6, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28696381/cost-saving-opportunities-in-nsclc-therapy-by-optimized-diagnostics
#10
Ilija Nenadić, Jeanine Staber, Susanne Dreier, Guus Simons, Verena Schildgen, Michael Brockmann, Oliver Schildgen
With an incidence of 68 new cases per 100,000 people per year, an estimated total number of up to 350,000 new non-small-cell lung cancer (NSCLC) cases are diagnosed each year in the European Union. Up to 10% of NSCLC patients are eligible for therapy with novel ALK (anaplastic lymphoma kinase) inhibitors, as they have been diagnosed with a mutation in the gene coding for ALK. The ALK inhibitor therapy costs add up to approx. 9,000 € per patient per month, with treatment durations of up to one year. Recent studies have shown that up to 10% of ALK cases are misdiagnosed by nearly 40% of pathologic investigations...
July 11, 2017: Cancers
https://www.readbyqxmd.com/read/28689043/pooled-systemic-efficacy-and-safety-data-from-the-pivotal-phase-ii-studies-np28673-and-np28761-of-alectinib-in-alk-positive-non-small-cell-lung-cancer
#11
James Chih-Hsin Yang, Sai-Hong Ignatius Ou, Luigi De Petris, Shirish Gadgeel, Leena Gandhi, Dong-Wan Kim, Fabrice Barlesi, Ramaswamy Govindan, Anne-Marie C Dingemans, Lucio Crino, Herve Lena, Sanjay Popat, Jin Seok Ahn, Eric Dansin, Sophie Golding, Walter Bordogna, Bogdana Balas, Peter N Morcos, Ali Zeaiter, Alice T Shaw
INTRODUCTION: Alectinib demonstrated clinical efficacy and an acceptable safety profile in two phase II studies (NP28761 and NP28673). Here we report pooled efficacy and safety data after 15 and 18 months' longer follow-up than the respective primary analyses. MATERIALS AND METHODS: Enrolled patients had ALK-positive NSCLC and had progressed on, or were intolerant to, crizotinib. Patients received oral alectinib 600 mg twice daily. The primary endpoint in both studies was objective response rate (ORR) assessed by an independent review committee (IRC) using Response Evaluation Criteria in Solid Tumors (RECIST v1...
July 5, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28680140/generation-of-novel-patient-derived-cic-dux4-sarcoma-xenografts-and-cell-lines
#12
Rieko Oyama, Mami Takahashi, Akihiko Yoshida, Marimu Sakumoto, Yoko Takai, Fusako Kito, Kumiko Shiozawa, Zhiwei Qiao, Yasuhito Arai, Tatsuhiro Shibata, Yoshihiro Araki, Makoto Endo, Akira Kawai, Tadashi Kondo
CIC-DUX4 sarcoma (CDS) is a group of rare, mesenchymal, small round cell tumours that harbour the unique CIC-DUX4 translocation, which causes aberrant gene expression. CDS exhibits an aggressive course and poor clinical outcome, thus novel therapeutic approaches are needed for CDS treatment. Although patient-derived cancer models are an essential modality to develop novel therapies, none currently exist for CDS. Thus, the present study successfully established CDS patient-derived xenografts and subsequently generated two CDS cell lines from the grafted tumours...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28676219/de-novo-cystic-brain-lesions-mimicking-neurocysticercosis-in-alk-positive-lung-cancer
#13
Su-Hyun Kim, Jae-Won Hyun, Ho Jin Kim, Ho-Shin Gwak, Sang Hyun Lee, Eun-Kyung Hong, Youngjoo Lee
Cystic brain metastases (CBM) have been recently reported in a minority of patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). All previously reported ALK-positive CBM developed during crizotinib treatment and were often asymptomatic and indolent, even without CNS-directed therapy. Thus, crizotinib was suggested as an etiologic agent for the development of CBM. Here, we report a case of de novo CBM in a patient with ALK-positive NSCLC prior to crizotinib treatment; the ALK-positive NSCLC had initially been misdiagnosed as neurocysticercosis because of the atypical radiological presentation of brain metastases...
August 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28676215/identification-of-a-novel-t1151k-alk-mutation-in-a-patient-with-alk-rearranged-nsclc-with-prior-exposure-to-crizotinib-and-ceritinib
#14
Viola W Zhu, J Jean Cui, Maria Fernandez-Rocha, Alexa B Schrock, Siraj M Ali, Sai-Hong Ignatius Ou
Patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) derive significant clinic benefit from treatment with ALK inhibitors. Crizotinib was the first approved tyrosine kinase inhibitor (TKI) for this distinct molecular subset of NSCLC. Disease progression on TKI inevitably arises secondary to diverse resistance mechanisms among which emergence of secondary ALK mutations is one of many ways in which tumor cells have adapted to survive. Therefore there is a clinical imperative to identify acquired ALK mutations via repeat tissue biopsy if clinically feasible...
August 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28675026/crizotinib-in-combination-with-everolimus-synergistically-inhibits-proliferation-of-alk-positive-anaplastic-large-cell-lymphoma
#15
Wendan Xu, Ji-Won Kim, Woo June Jung, Youngil Koh, Sung-Soo Yoon
Purpose: Anaplastic large cell lymphoma (ALCL) is a rare aggresive non-Hodgkin lymphoma, of which over 50% of cases have an aberrant NPM-ALK fusion protein. Both mTOR inhibitor everolimus and ALK inhibitor crizotinib have shown promising antitumor activity in ALK-positive cancer cell lines. However, their combined effect has not yet been investigated. Materials and Methods: We evaluated the anti-proliferative effects of everolimus and/or crizotinib in ALK-positive ALCL cell lines, Karpas 299 and SU-DHL-1, and lung adenocarcinoma cell line, NCI-H2228...
June 19, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28669346/crizotinib-versus-chemotherapy-on-alk-positive-nsclc-%C3%AF-a-systematic-review-of-efficacy-and-safety
#16
Mingxia Wang, Guanqi Wang, Haiyan Ma, Baoen Shan
Introduction Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011.We conducted a systematic review of clinical trials and retrospective studies to compare the efficacy and safety of crizotinib with chemotherapy. Methods We searched electronic databases from inception to Dec. 2016. Clinical trials and retrospective studies regarding crizotinib and crizotinib versus chemotherapy in treatment of NSCLC were eligible...
June 23, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28667686/pulsatile-crizotinib-treatment-for-brain-metastasis-in-a-patient-with-non-small-cell-lung-cancer
#17
S Wang, J Chen, Z Xie, L Xia, W Luo, J Li, Q Li, Z Yang
WHAT IS KNOWN AND OBJECTIVE: Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is a distinct subtype with patients showing peculiar clinicopathological features and dramatic responses to the ALK tyrosine kinase inhibitor crizotinib. Patients with this cancer variant have a dismal prognosis and limited treatment options when it has progressed to intracranial metastasis because of inadequate drug penetration into the central nervous system (CNS). Factors associated with response to TKI therapy have been reported to include pharmacokinetic and biodynamic resistance phenomena...
June 30, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28666189/oral-metronomic-topotecan-sensitizes-crizotinib-antitumor-activity-in-alk-f1174l-drug-resistant-neuroblastoma-preclinical-models
#18
Libo Zhang, Bing Wu, Sylvain Baruchel
BACKGROUND: Anaplastic lymphoma kinase (ALK) inhibitor crizotinib has proven to be effective in the treatment of ALK-mutated neuroblastoma, but crizotinib resistance was commonly observed in patients. We aimed to overcome crizotinib resistance by combining with the MEK inhibitor trametinib or low-dose metronomic (LDM) topotecan in preclinical neuroblastoma models. METHODS: We selected a panel of neuroblastoma cell lines carrying various ALK genetic aberrations to assess the therapeutic efficacy on cell proliferation in vitro...
June 27, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28646771/efficacy-of-alectinib-in-central-nervous-system-metastases-in-crizotinib-resistant-alk-positive-non-small-cell-lung-cancer-comparison-of-recist-1-1-and-rano-hgg-criteria
#19
Leena Gandhi, Sai-Hong Ignatius Ou, Alice T Shaw, Fabrice Barlesi, Anne-Marie C Dingemans, Dong-Wan Kim, D Ross Camidge, Brett G M Hughes, James C-H Yang, Javier de Castro, Lucio Crino, Hervé Léna, Pascal Do, Sophie Golding, Walter Bordogna, Ali Zeaiter, Ahmed Kotb, Shirish Gadgeel
BACKGROUND: Central nervous system (CNS) progression is common in patients with anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) receiving crizotinib. Next-generation ALK inhibitors have shown activity against CNS metastases, but accurate assessment of response and progression is vital. Data from two phase II studies in crizotinib-refractory ALK+ NSCLC were pooled to examine the CNS efficacy of alectinib, a CNS-active ALK inhibitor, using Response Evaluation Criteria in Solid Tumours (RECIST version 1...
July 10, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28638122/synergistic-effects-of-various-her-inhibitors-in-combination-with-igf-1r-c-met-and-src-targeting-agents-in-breast-cancer-cell-lines
#20
Aryan Stanley, G Hossein Ashrafi, Alan M Seddon, Helmout Modjtahedi
Overexpression of HER2 has been reported in around 25% of human breast cancers. Despite recent advances in HER2 targeted therapy, many patients still experience primary and secondary resistance to such treatments, the mechanisms for which are poorly understood. Here, we investigated the sensitivity of a panel of breast cancer cell lines to treatment with various types of HER-family inhibitors alone or in combination with other tyrosine kinase inhibitors or chemotherapeutic agents. We found that treatment with the second-generation irreversible HER-family inhibitors, particularly afatinib and neratinib, were more effective than treatment with the first-generation reversible inhibitors in inhibiting growth, migration and downstream cell signalling in breast cancer cells...
June 21, 2017: Scientific Reports
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