BACKGROUND: YM155, a small-molecule survivin suppressor, showed modest single-agent activity in a phase I study of heavily pretreated patients. This study was conducted to determine the activity of YM155 in patients with castration-resistant prostate cancer (CRPC) who received prior taxane therapy. PATIENTS AND METHODS: Patients received 4.8 mg/m(2)/day of YM155 over 168-h continuous i.v. infusion every 3 weeks. Study end points included prostate-specific antigen (PSA) response, objective tumor response, safety, progression-free survival (PFS) and overall survival (OS). RESULTS: Thirty-five patients were enrolled. Two of 32 (6.2%) assessable patients had a PSA response and 2 additional patients had PSA decrements >50% but not confirmed. One of 16 (6.2%) patients also had a partial response per RECIST V1. Median PFS and OS were 3.1 and 11.2 months, respectively. The most common adverse events were fatigue (63%), nausea (40%), anorexia (31%), constipation (31%), fever (26%) and vomiting (26%). CONCLUSIONS: YM155 has modest activity in taxane-pretreated CRPC with 25% of patients having prolonged stable disease (≥18 weeks). The regimen appears to be well tolerated. Based on the mechanism of action and preclinical evidence of synergy with docetaxel (Taxotere), YM155 combined with docetaxel is being evaluated in patients with CRPC.
BACKGROUND: YM155, a small-molecule survivin suppressor, showed modest single-agent activity in a phase I study of heavily pretreated patients. This study was conducted to determine the activity of YM155 in patients with castration-resistant prostate cancer (CRPC) who received prior taxane therapy. PATIENTS AND METHODS: Patients received 4.8 mg/m(2)/day of YM155 over 168-h continuous i.v. infusion every 3 weeks. Study end points included prostate-specific antigen (PSA) response, objective tumor response, safety, progression-free survival (PFS) and overall survival (OS). RESULTS: Thirty-five patients were enrolled. Two of 32 (6.2%) assessable patients had a PSA response and 2 additional patients had PSA decrements >50% but not confirmed. One of 16 (6.2%) patients also had a partial response per RECIST V1. Median PFS and OS were 3.1 and 11.2 months, respectively. The most common adverse events were fatigue (63%), nausea (40%), anorexia (31%), constipation (31%), fever (26%) and vomiting (26%). CONCLUSIONS: YM155 has modest activity in taxane-pretreated CRPC with 25% of patients having prolonged stable disease (≥18 weeks). The regimen appears to be well tolerated. Based on the mechanism of action and preclinical evidence of synergy with docetaxel (Taxotere), YM155 combined with docetaxel is being evaluated in patients with CRPC.
Authors: Qiuying Cheng; Xiang Ling; Andrew Haller; Takahito Nakahara; Kentaro Yamanaka; Aya Kita; Hiroshi Koutoku; Masahiro Takeuchi; Michael G Brattain; Fengzhi Li Journal: Int J Biochem Mol Biol Date: 2012-05-18
Authors: Bing Z Carter; Yihua Qiu; Xuelin Huang; Lixia Diao; Nianxiang Zhang; Kevin R Coombes; Duncan H Mak; Marina Konopleva; Jorge Cortes; Hagop M Kantarjian; Gordon B Mills; Michael Andreeff; Steven M Kornblau Journal: Blood Date: 2012-05-29 Impact factor: 22.113
Authors: Nicholas R Galloway; Carlos J Diaz Osterman; Karl Reiber; Jessica M S Jutzy; Fengzhi Li; Guangchao Sui; Ubaldo Soto; Nathan R Wall Journal: Biochem Biophys Res Commun Date: 2014-02-04 Impact factor: 3.575
Authors: James P Dean; Cynthia C Sprenger; Junxiang Wan; Kathleen Haugk; William J Ellis; Daniel W Lin; John M Corman; Bruce L Dalkin; Elahe Mostaghel; Peter S Nelson; Pinchas Cohen; Bruce Montgomery; Stephen R Plymate Journal: J Clin Endocrinol Metab Date: 2013-03-26 Impact factor: 5.958