BACKGROUND: The purpose of this study was to determine the clinical activity of patupilone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel. PATIENTS AND METHODS: Eligible patients had progressive disease within 6 months of receiving docetaxel. Patupilone was administered 10 mg/m2 i.v. every 3 weeks. The primary end point was the proportion of patients with a confirmed≥50% prostate-specific antigen (PSA) decline. RESULTS: Eighty-three patients were enrolled. At baseline, the median time to progression after prior docetaxel was 1.4 months (range 0-5.7). Gastrointestinal serious adverse events occurred in four of the six initial patients leading to a reduction of the starting dose of patupilone to 8 mg/m2 for subsequent patients. Grade 3-4 toxicity at this dose included diarrhea (22%), fatigue (21%), and anorexia (10%). One patient experienced grade 3-4 hematologic toxicity. A PSA decline of ≥50% occurred in 47% of patients. A partial measurable disease response occurred in 24% of assessable patients. A patient-reported pain response was observed in 59% of assessable patients. Median time to PSA progression was 6.1 months [95% confidence interval (CI) 4.7-8.0] and median overall survival was 11.3 months (95% CI 9.8-15.4). CONCLUSIONS: Patupilone at 8 mg/m2 was tolerable, had antitumor activity, and was associated with symptomatic improvement in patients previously treated with docetaxel.
BACKGROUND: The purpose of this study was to determine the clinical activity of patupilone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel. PATIENTS AND METHODS: Eligible patients had progressive disease within 6 months of receiving docetaxel. Patupilone was administered 10 mg/m2 i.v. every 3 weeks. The primary end point was the proportion of patients with a confirmed≥50% prostate-specific antigen (PSA) decline. RESULTS: Eighty-three patients were enrolled. At baseline, the median time to progression after prior docetaxel was 1.4 months (range 0-5.7). Gastrointestinal serious adverse events occurred in four of the six initial patients leading to a reduction of the starting dose of patupilone to 8 mg/m2 for subsequent patients. Grade 3-4 toxicity at this dose included diarrhea (22%), fatigue (21%), and anorexia (10%). One patient experienced grade 3-4 hematologic toxicity. A PSA decline of ≥50% occurred in 47% of patients. A partial measurable disease response occurred in 24% of assessable patients. A patient-reported pain response was observed in 59% of assessable patients. Median time to PSA progression was 6.1 months [95% confidence interval (CI) 4.7-8.0] and median overall survival was 11.3 months (95% CI 9.8-15.4). CONCLUSIONS:Patupilone at 8 mg/m2 was tolerable, had antitumor activity, and was associated with symptomatic improvement in patients previously treated with docetaxel.
Authors: Kevin R Kelly; Markus Zollinger; Frédéric Lozac'h; Eugene Tan; Alain Mita; Felix Waldmeier; Patrick Urban; Suraj Anand; Yanfeng Wang; Piet Swart; Chris Takimoto; Monica Mita Journal: Invest New Drugs Date: 2012-07-18 Impact factor: 3.850
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Authors: S Y Moorcraft; I Chau; C Peckitt; D Cunningham; S Rao; K L Yim; A Walther; C G C A Jackson; G Stamp; J Webb; G Smith; A Gillbanks; C Swanton Journal: Invest New Drugs Date: 2013-06-26 Impact factor: 3.850