PURPOSE: To determine the maximum tolerated dose (MTD) and characterize the dose-limiting toxicities (DLT) of tanespimycin when given in combination with bortezomib. EXPERIMENTAL DESIGN: Phase I dose-escalating trial using a standard cohort "3+3" design performed in patients with advanced solid tumors. Patients were given tanespimycin and bortezomib twice weekly for 2 weeks in a 3 week cycle (days 1, 4, 8, 11 every 21 days). RESULTS: Seventeen patients were enrolled in this study, fifteen were evaluable for toxicity, and nine patients were evaluable for tumor response. The MTD was 250 mg/m(2) of tanespimycin and 1.0 mg/m(2) of bortezomib when used in combination. DLTs of abdominal pain (13 %), complete atrioventricular block (7 %), fatigue (7 %), encephalopathy (7 %), anorexia (7 %), hyponatremia (7 %), hypoxia (7 %), and acidosis (7 %) were observed. There were no objective responses. One patient had stable disease. CONCLUSIONS: The recommended phase II dose for twice weekly 17-AAG and PS341 are 250 mg/m(2) and 1.0 mg/m(2), respectively, on days 1, 4, 8 and 11 of a 21 day cycle.
PURPOSE: To determine the maximum tolerated dose (MTD) and characterize the dose-limiting toxicities (DLT) of tanespimycin when given in combination with bortezomib. EXPERIMENTAL DESIGN: Phase I dose-escalating trial using a standard cohort "3+3" design performed in patients with advanced solid tumors. Patients were given tanespimycin and bortezomib twice weekly for 2 weeks in a 3 week cycle (days 1, 4, 8, 11 every 21 days). RESULTS: Seventeen patients were enrolled in this study, fifteen were evaluable for toxicity, and nine patients were evaluable for tumor response. The MTD was 250 mg/m(2) of tanespimycin and 1.0 mg/m(2) of bortezomib when used in combination. DLTs of abdominal pain (13 %), complete atrioventricular block (7 %), fatigue (7 %), encephalopathy (7 %), anorexia (7 %), hyponatremia (7 %), hypoxia (7 %), and acidosis (7 %) were observed. There were no objective responses. One patient had stable disease. CONCLUSIONS: The recommended phase II dose for twice weekly 17-AAG and PS341 are 250 mg/m(2) and 1.0 mg/m(2), respectively, on days 1, 4, 8 and 11 of a 21 day cycle.
Authors: Simon Pacey; Martin Gore; David Chao; Udai Banerji; James Larkin; Sarah Sarker; Karen Owen; Yasmin Asad; Florence Raynaud; Mike Walton; Ian Judson; Paul Workman; Tim Eisen Journal: Invest New Drugs Date: 2010-08-05 Impact factor: 3.850
Authors: Carol Aghajanian; Steven Soignet; Don S Dizon; Christine S Pien; Julian Adams; Peter J Elliott; Paul Sabbatini; Vincent Miller; Martee L Hensley; Sandra Pezzulli; Christina Canales; Adil Daud; David R Spriggs Journal: Clin Cancer Res Date: 2002-08 Impact factor: 12.531
Authors: Edward G Mimnaugh; Wanping Xu; Michele Vos; Xitong Yuan; Jennifer S Isaacs; Kheem S Bisht; David Gius; Len Neckers Journal: Mol Cancer Ther Date: 2004-05 Impact factor: 6.261
Authors: R C Schnur; M L Corman; R J Gallaschun; B A Cooper; M F Dee; J L Doty; M L Muzzi; J D Moyer; C I DiOrio; E G Barbacci Journal: J Med Chem Date: 1995-09-15 Impact factor: 7.446