A phase I-II study of docetaxel and atrasentan in men with castration-resistant metastatic prostate cancer.

Journal Article (Journal Article)

PURPOSE: The primary aims of this phase I-II study were to determine the maximum tolerated dose, dose-limiting toxicity, pharmacokinetics, and preliminary efficacy of the combination of docetaxel and the endothelin A receptor antagonist atrasentan as first-line treatment for men with metastatic castration-resistant prostate cancer. EXPERIMENTAL DESIGN: Patients were treated with docetaxel at doses ranging from 60 to 75 mg/m(2) every 21 days, with daily oral atrasentan 10 mg starting on day 3. Patients were treated until evidence of disease progression or unacceptable toxicity. RESULTS: Thirty-one patients were enrolled over three docetaxel dose levels (8 at 60 mg/m(2), 19 at 70 mg/m(2), and 4 at 75 mg/m(2)) including dose expansion at 70 mg/m(2). The maximum tolerated dose of docetaxel was 70 to 75 mg/m(2). Drug-related grade 3-4 toxicities included neutropenia (50-63%) and febrile neutropenia (16-25%); other grade 1-2 toxicities included fatigue, peripheral edema, diarrhea, headache, rhinitis, anorexia, and nausea. Confirmed prostate-specific antigen (PSA) responses were observed in 23% [95% confidence interval (95% CI), 10-41%]; the rate of >30% declines in PSA was 35% (95% CI, 19-55%). Median overall survival was 17.6 months (95% CI, 13.0-23.2) and median progression-free survival was 4.2 months (95% CI, 2.3-5.8). Significant declines in bone alkaline phosphatase and serum N-telopeptides were observed with therapy. CONCLUSIONS: The maximum tolerated dose of every-3-week docetaxel with 10 mg atrasentan is 70 to 75 mg/m(2). Overall survival and progression-free survival are comparable to that seen with docetaxel and prednisone, whereas the rates of PSA decline are slightly lower than expected. A phase III study of this combination with prednisone has been initiated and is ongoing.

Full Text

Duke Authors

Cited Authors

  • Armstrong, AJ; Creel, P; Turnbull, J; Moore, C; Jaffe, TA; Haley, S; Petros, W; Yenser, S; Gockerman, JP; Sleep, D; Hurwitz, H; George, DJ

Published Date

  • October 1, 2008

Published In

Volume / Issue

  • 14 / 19

Start / End Page

  • 6270 - 6276

PubMed ID

  • 18829508

International Standard Serial Number (ISSN)

  • 1078-0432

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-08-1085


  • eng

Conference Location

  • United States