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      Crizotinib, an Effective Agent in ROS1-Rearranged Adenocarcinoma of Lungs: A Case Report

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction:

          ROS1 rearrangement has recently emerged as a new molecular subtype in non–small-cell lung cancer (NSCLC) and is predominantly found in lung adenocarcinoma compared with other oncogenes such as EGFR, KRAS, or ALK. It has been identified in only 1% to 2% of NSCLC cases.

          Case Report:

          We report a case of 52-year-old man (nonsmoker) with a medical history of allergic rhinitis and bronchial asthma. Histopathologic examination of bronchoscopic-guided biopsy showed adenocarcinoma histology on September 2015. After 2 months, he developed left-sided pneumonia for which he was treated with multiple intravenous antibiotics. In the meantime, fiberoptic bronchoscopy was done which revealed purulent secretion from right upper lobe and narrowed opening of right middle lobe. His cancer symptoms got worsened and bronchial biopsy showed EGFR mutation negative. For further diagnosis, fluorescent in situ hybridization test was done which showed ROS1 mutation positive. By then, the patient was started with crizotinib 250 mg twice daily for ROS1 mutation in July 2016. Later, patient appears to benefit from treatment with crizotinib. X-ray report and positron emission tomographic-computed tomographic scan revealed that the patient was overall better with clear chest and well tolerated with the therapy. Crizotinib was approved on March 11, 2016 by Food and Drug Administration for the treatment of patients with ROS1-positive NSCLC.

          Conclusions:

          In this report, crizotinib showed marked antitumor activity in patients with advanced ROS1 rearrangement, a third molecular subgroup of NSCLC.

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          Most cited references 17

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          Crizotinib versus chemotherapy in advanced ALK-positive lung cancer.

          In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown. We conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen. Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival. The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group (hazard ratio for progression or death with crizotinib, 0.49; 95% confidence interval [CI], 0.37 to 0.64; P<0.001). The response rates were 65% (95% CI, 58 to 72) with crizotinib, as compared with 20% (95% CI, 14 to 26) with chemotherapy (P<0.001). An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, 0.68 to 1.54; P=0.54). Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, alopecia, and dyspnea. Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy. Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement. (Funded by Pfizer; ClinicalTrials.gov number, NCT00932893.).
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            ALK in lung cancer: past, present, and future.

            In 2007, scientists discovered that anaplastic lymphoma kinase (ALK) gene rearrangements are present in a small subset of non-small-cell lung cancers. ALK-positive cancers are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib. Phase I and II studies of crizotinib in ALK-positive lung cancer demonstrated impressive activity and clinical benefit, leading to rapid US Food and Drug Administration approval in 2011. Although crizotinib induces remissions and extends the lives of patients, cures are not achieved as resistance to therapy develops. In this review, we will discuss the history of this field, current diagnostic and treatment practices, and future challenges and opportunities to advance outcomes for patients with ALK-positive lung cancers.
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              EML4-ALK: honing in on a new target in non-small-cell lung cancer.

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                Author and article information

                Journal
                Clin Med Insights Case Rep
                Clin Med Insights Case Rep
                ICR
                spicr
                Clinical Medicine Insights. Case Reports
                SAGE Publications (Sage UK: London, England )
                1179-5476
                15 January 2018
                2018
                : 11
                Affiliations
                [1 ]Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, India
                [2 ]Department of Medical Oncology and Hematology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, India
                Author notes
                Meenu Vijayan, Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi 682041, India. Email: meenuvijayan@ 123456aims.amrita.edu
                Article
                10.1177_1179547617749615 ICR-0043014
                10.1177/1179547617749615
                5772496
                © The Author(s) 2018

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                Categories
                Case Report
                Custom metadata
                January-December 2018

                Medicine

                ros1 rearrangement, nsclc, fish test, crizotinib, antitumor activity

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