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  1. Article ; Online: Predictive significance of circulating tumor DNA against patients with T790M-positive EGFR-mutant NSCLC receiving osimertinib

    Ou Yamaguchi / Norimitsu Kasahara / Hiroshi Soda / Hisao Imai / Ichiro Naruse / Hiroyuki Yamaguchi / Miki Itai / Kohei Taguchi / Megumi Uchida / Noriaki Sunaga / Toshitaka Maeno / Koichi Minato / Hiromi Tomono / Daiki Ogawara / Hiroshi Mukae / Yu Miura / Ayako Shiono / Atsuto Mouri / Hiroshi Kagamu /
    Kyoichi Kaira

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    2023  Volume 10

    Abstract: Abstract Circulating tumor DNA (ctDNA) provides molecular information on tumor heterogeneity. The prognostic usefulness of ctDNA after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are limited. Therefore, the ... ...

    Abstract Abstract Circulating tumor DNA (ctDNA) provides molecular information on tumor heterogeneity. The prognostic usefulness of ctDNA after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are limited. Therefore, the present study evaluated ctDNA during osimertinib administration as a second-line or more setting to identify the relationship between EGFR mutation levels and outcomes in patients with advanced non-small cell lung cancer (NSCLC). Forty patients with EGFR T790M-positive NSCLC receiving osimertinib after prior EGFR-TKI treatment were registered. Plasma samples were collected at osimertinib pretreatment, after 1 month of treatment, and at the time of progressive disease (PD). ctDNA analysis was performed by digital polymerase chain reaction. The detection rate of copy numbers of exon 19 deletion, L858R, and T790M in plasma samples was significantly lower 1 month after osimertinib than at pretreatment, and significantly higher at PD than at 1 month, whereas that of C797S was significantly higher at PD than at 1 month. No statistically significant difference was observed in the copy numbers of exon 19 deletion, L858R, T790M, and C797S between complete response or partial response and stable disease or PD. The detection of T790M at PD after osimertinib initiation was a significant independent prognostic factor for predicting shorter prognosis, and the presence of major EGFR mutations at pretreatment and PD was closely linked to worse survival after osimertinib initiation. Molecular testing based on ctDNA is helpful for predicting outcomes of osimertinib treatment in T790M-positive NSCLC after previous EGFR-TKI treatment.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Efficacy and safety of amrubicin hydrochloride for treatment of relapsed small cell lung cancer

    Daiki Ogawara / Minoru Fukuda / Yoichi Nakamura

    Cancer Management and Research, Vol 2010, Iss default, Pp 191-

    2010  Volume 195

    Abstract: Daiki Ogawara1, Minoru Fukuda2, Yoichi Nakamura3, Shigeru Kohno31Department of Medicine, Sasebo Central Hospital, 2Department of Medicine, Nagasaki Municipal Hospital, 3Second Department of Internal Medicine, Nagasaki University School of Medicine, ... ...

    Abstract Daiki Ogawara1, Minoru Fukuda2, Yoichi Nakamura3, Shigeru Kohno31Department of Medicine, Sasebo Central Hospital, 2Department of Medicine, Nagasaki Municipal Hospital, 3Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, JapanAbstract: Long-term survival is quite uncommon in refractory small cell lung cancer (SCLC) patients, with less than 25% of patients with limited-stage disease and 1%–2% of patients with extensive-stage disease remaining alive at five years. Recent clinical studies have demonstrated the promising efficacy of amrubicin for patients with relapsed SCLC. This review presents the results of clinical studies showing the efficacy and safety of amrubicin for the treatment of relapsed SCLC. Amrubicin is a synthetic anthracycline agent with a similar structure to doxorubicin, in which the hydroxyl group at position 9 in amrubicin is replaced by an amino group to enhance efficacy. It is converted to an active metabolite, amrubicinol, which is 5–54 times more active than amrubicin. Amrubicin and amrubicinol are inhibitors of DNA topoisomerase II, exerting their cytotoxic effects by stabilizing a topoisomerase II-mediated cleavable complex. The toxicity of amrubicin is similar to that of doxorubicin, although amrubicin shows almost no cardiotoxicity. In the relevant trials, amrubicin was administered intravenously at a dose of 35–40 mg/m2 on days 1–3 every three weeks. The response rate was 34%–52% and median survival times were 8.1–12.0 months. Common hematologic toxicities included neutropenia, leucopenia, anemia, thrombocytopenia, and febrile neutropenia. Nonhematologic adverse events included Grade 3–4 anorexia, asthenia, hyponatremia, and nausea. The results of the studies which demonstrated the efficacy of monotherapy for relapsed SCLC involved mainly Japanese patients. Therefore, it is necessary to conduct more clinical studies in non-Japanese patients to confirm the efficacy of amrubicin.Keywords: amrubicin, amrubicinol, small cell lung cancer, relapse
    Keywords Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 550 ; 610
    Language English
    Publishing date 2010-08-01T00:00:00Z
    Publisher Dove Medical Press
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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