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( Hayoung Choi ),( Jin Sun Chang ),( In Jae Oh ),( Kyu Sik Kim ),( Young Chul Kim ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1
Background: Afatinib is an irreversible ErbB family blocker that inhibits EGFR with activating mutations as well as the T790M resistance mutations. In non-small cell lung cancer (NSCLC), afatinib has been evaluated in the LUX-Lung trials, with improvement in progression-free survival (PFS) in patients with acquired resistance to prior EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment. This study investigated afatinib under a Named Patient Use (NPU) program at a single institution in Korea. Methods: We analyzed 53 patients with stage IV NSCLC that had been treated with = 1 platinum based chemotherapy, and with activating EGFR mutation or disease control for = 6 months with prior EGFR-TKI. The daily dose of afatinib was started with 50mg, which was decreased to 40mg and 30mg according to adverse events. Results: Treatment duration of afatinib was from 4 to 377 days with a mean of 102 days. Of 53 analyzed patients, 2 received afatinib as 3rd line treatment, 24 as 4th line, 15 as 5th line and 12 as = 6th line. Nine patients achieved partial remission, 28 stable disease, and 9 progression, and 7 not-evaluable resulting in a response rate of 16.9% and a disease control rate (DCR) of 69.8%. Grade 3 skin rash and diarrhea occurred in one and 8 patients, respectively, and dosage reductions of afatinib were required in 28 patients, to 40mg in 20 and to 30mg in 8. Toxicities leading to drug discontinuation were experienced by 4 patients. Median PFS and overall survival were 4.6 months (95% CI, 3.6 - 5.5 months) and 13.4 months (9.2 - 17.6 months), respectively. Conclusions: Afatinib demonstrated DCR of about 70% and PFS of 4.6 months in patients with NSCLC after failure of prior EGFR-TKI.
Choi, Hayoung,Kim, Su-Young,Lee, Hyun,Jhun, Byung Woo,Park, Hye Yun,Jeon, Kyeongman,Kim, Dae Hun,Huh, Hee Jae,Ki, Chang-Seok,Lee, Nam Yong,Lee, Seung-Heon,Shin, Sung Jae,Daley, Charles L.,Koh, Won-Jun American Society for Microbiology 2017 Antimicrobial Agents and Chemotherapy Vol.61 No.2
<P>Macrolide antibiotics are cornerstones in the treatment of Mycobacterium massiliense lung disease. Despite the emergence of resistance, limited data on macrolide-resistant M. massiliense lung disease are available. This study evaluated the clinical features and treatment outcomes of patients and the molecular characteristics of macrolide-resistant M. massiliense isolates. We performed a retrospective review of medical records and genetic analyses of clinical isolates from 15 patients who had macrolide-resistant M. massiliense lung disease between September 2005 and February 2015. Nine patients (60%) had the nodular bronchiectatic form of the disease, and six (40%) had the fibrocavitary form. Before the detection of macrolide resistance, three patients (20%) were treated with macrolide monotherapy, four (27%) with therapy for presumed Mycobacterium avium complex infections, and eight (53%) with combination antibiotic therapy for M. massiliense lung disease. The median treatment duration after the detection of resistance was 18.7 months (inter-quartile range, 11.2 to 39.8 months). Treatment outcomes were poor, with a favorable outcome being achieved for only one patient (7%), who underwent surgery in addition to antibiotic therapy. The 1-, 3-, and 5-year mortality rates were 7, 13, and 33%, respectively. Of the 15 clinical isolates, 14 (93%) had point mutations at position 2058 (n = 9) or 2059 (n = 5) of the 23S rRNA gene, resulting in macrolide resistance. Our study indicates that treatment outcomes are poor and mortality rates are high after the development of macrolide resistance in patients with M. massiliense lung disease. Thus, preventing the development of macrolide resistance should be a key consideration during treatment.</P>