Investigational New Drugs

, Volume 29, Issue 6, pp 1441–1448

Oral enzastaurin in prostate cancer: A two-cohort phase II trial in patients with PSA progression in the non-metastatic castrate state and following docetaxel-based chemotherapy for castrate metastatic disease

  • Robert Dreicer
  • Jorge Garcia
  • Maha Hussain
  • Brian Rini
  • Nicholas Vogelzang
  • Sandy Srinivas
  • Bradley Somer
  • Yan D. Zhao
  • Marek Kania
  • Derek Raghavan
PHASE II STUDIES

DOI: 10.1007/s10637-010-9428-0

Cite this article as:
Dreicer, R., Garcia, J., Hussain, M. et al. Invest New Drugs (2011) 29: 1441. doi:10.1007/s10637-010-9428-0

Summary

Purpose: Enzastaurin is an oral serine/threonine kinase inhibitor of the beta isoform of protein kinase C that may have therapeutic activity in prostate cancer. We explored the efficacy of enzastaurin on two cohorts of patients with prostate cancer progression in the castrate state. Patients and Methods: A two-cohort phase II trial was conducted, with both groups participating simultaneously. Cohort 1 consisted of patients with non-metastatic castrate prostate-specific antigen progressive disease. Cohort 2 consisted of patients with castrate metastatic disease with progression following docetaxel-based chemotherapy. Patients in both cohorts received 500 mg/day enzastaurin. Results: Therapy was well tolerated in both cohorts. One complete response was observed in Cohort 1, with limited activity in the majority of patients. In Cohort 2, no objective responses were seen and the median progression-free survival (11 weeks [90% confidence interval: 7.6, 11.7]) did not differ from the historical control. Conclusions: Enzastaurin as a single agent has limited activity in castrate progressive prostate cancer. Evaluation in combination with docetaxel is ongoing.

Keywords

Prostate cancerEnzastaurinProstate-specific antigenClinical trial

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Robert Dreicer
    • 1
  • Jorge Garcia
    • 1
  • Maha Hussain
    • 2
  • Brian Rini
    • 1
  • Nicholas Vogelzang
    • 3
  • Sandy Srinivas
    • 4
  • Bradley Somer
    • 5
  • Yan D. Zhao
    • 6
  • Marek Kania
    • 6
  • Derek Raghavan
    • 1
  1. 1.Department of Solid Tumor Oncology, Taussig Cancer InstituteCleveland ClinicClevelandUSA
  2. 2.University of Michigan Comprehensive Cancer CenterAnn ArborUSA
  3. 3.Nevada Cancer InstituteLas VegasUSA
  4. 4.Stanford University Medical CenterStanfordUSA
  5. 5.The West ClinicMemphisUSA
  6. 6.Eli Lilly and CompanyIndianapolisUSA