BACKGROUND: In vitro data suggest that panobinostat (LBH589), a pan-deacetylase inhibitor, may add therapeutic benefit in the treatment of small-cell lung cancer (SCLC) with regression of tumors. METHODS: This multicenter, nonrandomized phase 2 trial was designed to evaluate antitumor activity of LBH589 in patients with previously treated SCLC. Patients received LBH589 administered intravenously at a dose of 20 mg/mq (days 1-8) every 21 days. RESULTS: A total of 21 patients with extensive- or limited-stage SCLC were enrolled. Patients received a median of two cycles (range, 1-6). LBH589 was well tolerated, and the most common toxicities were grade 1 to 2 gastrointestinal disorders (nausea 38%, diarrhea 24%, vomiting 19%), grade 1 to 2 thrombocytopenia (14.3%). Of 19 patients evaluable for efficacy, two cases showed shrinkages more than 30% at first assessment, with time to progression of 14 and 21 weeks, respectively, and there were three long disease stabilizations of 12, 10, and 13 weeks. The study was prematurely closed because of a lack of activity. CONCLUSION: This is the first report of a pan-deacetylase inhibitor inducing tumor shrinkage and sustained stable disease in SCLC. We believe that although the trial was prematurely discontinued, modest clinical activity of LBH589 combined with a favorable safety profile in pretreated SCLC patients was observed, which warrants further exploration of the potential contribution of LBH589 in other trials.
BACKGROUND: In vitro data suggest that panobinostat (LBH589), a pan-deacetylase inhibitor, may add therapeutic benefit in the treatment of small-cell lung cancer (SCLC) with regression of tumors. METHODS: This multicenter, nonrandomized phase 2 trial was designed to evaluate antitumor activity of LBH589 in patients with previously treated SCLC. Patients received LBH589 administered intravenously at a dose of 20 mg/mq (days 1-8) every 21 days. RESULTS: A total of 21 patients with extensive- or limited-stage SCLC were enrolled. Patients received a median of two cycles (range, 1-6). LBH589 was well tolerated, and the most common toxicities were grade 1 to 2 gastrointestinal disorders (nausea 38%, diarrhea 24%, vomiting 19%), grade 1 to 2 thrombocytopenia (14.3%). Of 19 patients evaluable for efficacy, two cases showed shrinkages more than 30% at first assessment, with time to progression of 14 and 21 weeks, respectively, and there were three long disease stabilizations of 12, 10, and 13 weeks. The study was prematurely closed because of a lack of activity. CONCLUSION: This is the first report of a pan-deacetylase inhibitor inducing tumor shrinkage and sustained stable disease in SCLC. We believe that although the trial was prematurely discontinued, modest clinical activity of LBH589 combined with a favorable safety profile in pretreated SCLCpatients was observed, which warrants further exploration of the potential contribution of LBH589 in other trials.
Authors: Mariacarmela Santarpia; Maria Grazia Daffinà; Niki Karachaliou; Maria González-Cao; Chiara Lazzari; Giuseppe Altavilla; Rafael Rosell Journal: Transl Lung Cancer Res Date: 2016-02
Authors: Tao Yan-Fang; Li Zhi-Heng; Xu Li-Xiao; Fang Fang; Lu Jun; Li Gang; Cao Lan; Wang Na-Na; Du Xiao-Juan; Sun Li-Chao; Zhao Wen-Li; Xiao Pei-Fang; Zhao He; Su Guang-Hao; Li Yan-Hong; Li Yi-Ping; Xu Yun-Yun; Zhou Hui-Ting; Wu Yi; Jin Mei-Fang; Liu Lin; Ni Jian; Hu Shao-Yan; Zhu Xue-Ming; Feng Xing; Wang Jian; Pan Jian Journal: PLoS One Date: 2015-07-15 Impact factor: 3.240
Authors: Gary Wildey; Yanwen Chen; Ian Lent; Lindsay Stetson; John Pink; Jill S Barnholtz-Sloan; Afshin Dowlati Journal: PLoS One Date: 2014-09-08 Impact factor: 3.240
Authors: Martina Korfei; Daniel Stelmaszek; BreAnne MacKenzie; Sylwia Skwarna; Shashipavan Chillappagari; Anna C Bach; Clemens Ruppert; Shigeki Saito; Poornima Mahavadi; Walter Klepetko; Ludger Fink; Werner Seeger; Joseph A Lasky; Soni S Pullamsetti; Oliver H Krämer; Andreas Guenther Journal: PLoS One Date: 2018-11-27 Impact factor: 3.240