PubMed:25537159 JSONTXT

{"project":"Inflammaging","denotations":[{"id":"T1","span":{"begin":0,"end":163},"obj":"Sentence"},{"id":"T2","span":{"begin":164,"end":175},"obj":"Sentence"},{"id":"T3","span":{"begin":176,"end":232},"obj":"Sentence"},{"id":"T4","span":{"begin":233,"end":289},"obj":"Sentence"},{"id":"T5","span":{"begin":290,"end":490},"obj":"Sentence"},{"id":"T6","span":{"begin":491,"end":677},"obj":"Sentence"},{"id":"T7","span":{"begin":678,"end":699},"obj":"Sentence"},{"id":"T8","span":{"begin":700,"end":982},"obj":"Sentence"},{"id":"T9","span":{"begin":983,"end":1105},"obj":"Sentence"},{"id":"T10","span":{"begin":1106,"end":1114},"obj":"Sentence"},{"id":"T11","span":{"begin":1115,"end":1274},"obj":"Sentence"},{"id":"T12","span":{"begin":1275,"end":1368},"obj":"Sentence"},{"id":"T13","span":{"begin":1369,"end":1492},"obj":"Sentence"},{"id":"T14","span":{"begin":1493,"end":1736},"obj":"Sentence"},{"id":"T15","span":{"begin":1737,"end":1748},"obj":"Sentence"},{"id":"T16","span":{"begin":1749,"end":1987},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":163},"obj":"Sentence"},{"id":"T2","span":{"begin":164,"end":175},"obj":"Sentence"},{"id":"T3","span":{"begin":176,"end":232},"obj":"Sentence"},{"id":"T4","span":{"begin":233,"end":289},"obj":"Sentence"},{"id":"T5","span":{"begin":290,"end":490},"obj":"Sentence"},{"id":"T6","span":{"begin":491,"end":677},"obj":"Sentence"},{"id":"T7","span":{"begin":678,"end":699},"obj":"Sentence"},{"id":"T8","span":{"begin":700,"end":982},"obj":"Sentence"},{"id":"T9","span":{"begin":983,"end":1105},"obj":"Sentence"},{"id":"T10","span":{"begin":1106,"end":1114},"obj":"Sentence"},{"id":"T11","span":{"begin":1115,"end":1274},"obj":"Sentence"},{"id":"T12","span":{"begin":1275,"end":1368},"obj":"Sentence"},{"id":"T13","span":{"begin":1369,"end":1492},"obj":"Sentence"},{"id":"T14","span":{"begin":1493,"end":1736},"obj":"Sentence"},{"id":"T15","span":{"begin":1737,"end":1748},"obj":"Sentence"},{"id":"T16","span":{"begin":1749,"end":1987},"obj":"Sentence"}],"text":"A neoadjuvant, randomized, open-label phase II trial of afatinib versus trastuzumab versus lapatinib in patients with locally advanced HER2-positive breast cancer.\nBACKGROUND: Chemotherapy is standard neoadjuvant treatment of LA BC. Patients with HER2-positive BC require targeted therapy. Trastuzumab and pertuzumab, which target HER2, with chemotherapy are approved as neoadjuvant therapy, however, treatments with different mechanisms of action might provide a broader range of activity. In this study we evaluated the efficacy and safety of the irreversible ErbB family blocker afatinib, versus trastuzumab or lapatinib in the neoadjuvant treatment of HER2-positive, LA BC.\nPATIENTS AND METHODS: Treatment-naive, HER2-positive BC patients with stage IIIA, B, C or inflammatory disease were randomized 1:1:1 to daily afatinib (50 mg), lapatinib (1500 mg), or weekly trastuzumab (4 mg/kg loading dose, then 2 mg/kg/wk) for 6 weeks until surgery or follow-up neoadjuvant treatment. The primary end point was objective response rate according to Response Evaluation Criteria in Solid Tumors (version 1.0).\nRESULTS: Recruitment was stopped early because of slow patient enrollment; 29 patients were randomized to afatinib (n = 10), lapatinib (n = 8), or trastuzumab (n = 11). Objective response was seen in 8 afatinib-, 6 lapatinib-, and 4 trastuzumab-treated patients. Eleven patients had stable disease (best response); 1 lapatinib- and 1 trastuzumab-treated patient had progressive disease. All 10 afatinib-treated patients experienced drug-related adverse events (commonly diarrhea, dermatitis acneiform, and paronychia) versus 6 of 8 lapatinib- (diarrhea and rash) and 5 of 11 trastuzumab-treated patients (vomiting and arthralgia).\nCONCLUSION: Afatinib demonstrated clinical activity that compared favorably to trastuzumab and lapatinib for neoadjuvant treatment of HER2-positive BC, with a safety profile consistent with epidermal growth factor receptor tyrosine kinase inhibitors."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"25537159-0#135#139#gene2064","span":{"begin":135,"end":139},"obj":"gene2064"},{"id":"25537159-0#149#162#diseaseC0006142","span":{"begin":149,"end":162},"obj":"diseaseC0006142"},{"id":"25537159-0#149#162#diseaseC0678222","span":{"begin":149,"end":162},"obj":"diseaseC0678222"}],"relations":[{"id":"135#139#gene2064149#162#diseaseC0006142","pred":"associated_with","subj":"25537159-0#135#139#gene2064","obj":"25537159-0#149#162#diseaseC0006142"},{"id":"135#139#gene2064149#162#diseaseC0678222","pred":"associated_with","subj":"25537159-0#135#139#gene2064","obj":"25537159-0#149#162#diseaseC0678222"}],"text":"A neoadjuvant, randomized, open-label phase II trial of afatinib versus trastuzumab versus lapatinib in patients with locally advanced HER2-positive breast cancer.\nBACKGROUND: Chemotherapy is standard neoadjuvant treatment of LA BC. Patients with HER2-positive BC require targeted therapy. Trastuzumab and pertuzumab, which target HER2, with chemotherapy are approved as neoadjuvant therapy, however, treatments with different mechanisms of action might provide a broader range of activity. In this study we evaluated the efficacy and safety of the irreversible ErbB family blocker afatinib, versus trastuzumab or lapatinib in the neoadjuvant treatment of HER2-positive, LA BC.\nPATIENTS AND METHODS: Treatment-naive, HER2-positive BC patients with stage IIIA, B, C or inflammatory disease were randomized 1:1:1 to daily afatinib (50 mg), lapatinib (1500 mg), or weekly trastuzumab (4 mg/kg loading dose, then 2 mg/kg/wk) for 6 weeks until surgery or follow-up neoadjuvant treatment. The primary end point was objective response rate according to Response Evaluation Criteria in Solid Tumors (version 1.0).\nRESULTS: Recruitment was stopped early because of slow patient enrollment; 29 patients were randomized to afatinib (n = 10), lapatinib (n = 8), or trastuzumab (n = 11). Objective response was seen in 8 afatinib-, 6 lapatinib-, and 4 trastuzumab-treated patients. Eleven patients had stable disease (best response); 1 lapatinib- and 1 trastuzumab-treated patient had progressive disease. All 10 afatinib-treated patients experienced drug-related adverse events (commonly diarrhea, dermatitis acneiform, and paronychia) versus 6 of 8 lapatinib- (diarrhea and rash) and 5 of 11 trastuzumab-treated patients (vomiting and arthralgia).\nCONCLUSION: Afatinib demonstrated clinical activity that compared favorably to trastuzumab and lapatinib for neoadjuvant treatment of HER2-positive BC, with a safety profile consistent with epidermal growth factor receptor tyrosine kinase inhibitors."}

{"project":"wangzhuo19_800","denotations":[{"id":"T1","span":{"begin":290,"end":301},"obj":"CI"},{"id":"T2","span":{"begin":306,"end":316},"obj":"CI"},{"id":"T3","span":{"begin":582,"end":590},"obj":"CI"},{"id":"T4","span":{"begin":599,"end":610},"obj":"CI"},{"id":"T5","span":{"begin":614,"end":623},"obj":"CI"},{"id":"T6","span":{"begin":820,"end":828},"obj":"CI"},{"id":"T7","span":{"begin":838,"end":847},"obj":"CI"},{"id":"T8","span":{"begin":869,"end":880},"obj":"CI"},{"id":"T9","span":{"begin":1212,"end":1220},"obj":"CI"},{"id":"T10","span":{"begin":1231,"end":1240},"obj":"CI"},{"id":"T11","span":{"begin":1253,"end":1264},"obj":"CI"},{"id":"T12","span":{"begin":1308,"end":1316},"obj":"CI"},{"id":"T13","span":{"begin":1321,"end":1330},"obj":"CI"},{"id":"T14","span":{"begin":1339,"end":1350},"obj":"CI"},{"id":"T15","span":{"begin":1423,"end":1432},"obj":"CI"},{"id":"T16","span":{"begin":1440,"end":1451},"obj":"CI"},{"id":"T17","span":{"begin":1500,"end":1508},"obj":"CI"},{"id":"T18","span":{"begin":1638,"end":1647},"obj":"CI"},{"id":"T19","span":{"begin":1681,"end":1692},"obj":"CI"},{"id":"T20","span":{"begin":1749,"end":1757},"obj":"CI"},{"id":"T21","span":{"begin":1816,"end":1827},"obj":"CI"},{"id":"T22","span":{"begin":1832,"end":1841},"obj":"CI"},{"id":"T24","span":{"begin":226,"end":231},"obj":"DP"},{"id":"T25","span":{"begin":247,"end":263},"obj":"DP"},{"id":"T26","span":{"begin":135,"end":162},"obj":"DP"},{"id":"T27","span":{"begin":656,"end":676},"obj":"DP"},{"id":"T28","span":{"begin":717,"end":742},"obj":"DP"},{"id":"T29","span":{"begin":1871,"end":1887},"obj":"DP"}],"text":"A neoadjuvant, randomized, open-label phase II trial of afatinib versus trastuzumab versus lapatinib in patients with locally advanced HER2-positive breast cancer.\nBACKGROUND: Chemotherapy is standard neoadjuvant treatment of LA BC. Patients with HER2-positive BC require targeted therapy. Trastuzumab and pertuzumab, which target HER2, with chemotherapy are approved as neoadjuvant therapy, however, treatments with different mechanisms of action might provide a broader range of activity. In this study we evaluated the efficacy and safety of the irreversible ErbB family blocker afatinib, versus trastuzumab or lapatinib in the neoadjuvant treatment of HER2-positive, LA BC.\nPATIENTS AND METHODS: Treatment-naive, HER2-positive BC patients with stage IIIA, B, C or inflammatory disease were randomized 1:1:1 to daily afatinib (50 mg), lapatinib (1500 mg), or weekly trastuzumab (4 mg/kg loading dose, then 2 mg/kg/wk) for 6 weeks until surgery or follow-up neoadjuvant treatment. The primary end point was objective response rate according to Response Evaluation Criteria in Solid Tumors (version 1.0).\nRESULTS: Recruitment was stopped early because of slow patient enrollment; 29 patients were randomized to afatinib (n = 10), lapatinib (n = 8), or trastuzumab (n = 11). Objective response was seen in 8 afatinib-, 6 lapatinib-, and 4 trastuzumab-treated patients. Eleven patients had stable disease (best response); 1 lapatinib- and 1 trastuzumab-treated patient had progressive disease. All 10 afatinib-treated patients experienced drug-related adverse events (commonly diarrhea, dermatitis acneiform, and paronychia) versus 6 of 8 lapatinib- (diarrhea and rash) and 5 of 11 trastuzumab-treated patients (vomiting and arthralgia).\nCONCLUSION: Afatinib demonstrated clinical activity that compared favorably to trastuzumab and lapatinib for neoadjuvant treatment of HER2-positive BC, with a safety profile consistent with epidermal growth factor receptor tyrosine kinase inhibitors."}