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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

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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.

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Acknowledgements

The authors thank all of the patients and institutions involved in this study and Eli Lilly and Company for its sponsorship and funding. The authors also thank Mary Dugan Wood who provided medical writing services on behalf of Eli Lilly and Company, Joseph Durrant (i3 Statprobe,Ann Arbor, MI) for editorial assistance, and Flora Ayeni for assistance with the statistical analyses.

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Authors and Affiliations

  1. Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, 9500 Euclid Ave R35, Cleveland, OH, 44195, USA

    Robert Dreicer, Jorge Garcia, Brian Rini & Derek Raghavan

  2. University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA

    Maha Hussain

  3. Nevada Cancer Institute, Las Vegas, NV, USA

    Nicholas Vogelzang

  4. Stanford University Medical Center, Stanford, CA, USA

    Sandy Srinivas

  5. The West Clinic, Memphis, TN, USA

    Bradley Somer

  6. Eli Lilly and Company, Indianapolis, IN, USA

    Yan D. Zhao & Marek Kania

Authors
  1. Robert Dreicer
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  2. Jorge Garcia
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  3. Maha Hussain
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  4. Brian Rini
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  5. Nicholas Vogelzang
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  6. Sandy Srinivas
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  7. Bradley Somer
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  8. Yan D. Zhao
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  9. Marek Kania
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  10. Derek Raghavan
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Corresponding author

Correspondence to Robert Dreicer.

Additional information

Trial registry: ClinicalTrials.gov.Registry identifier number: NCT00428714.

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Dreicer, R., Garcia, J., Hussain, M. et al. 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. Invest New Drugs 29, 1441–1448 (2011). https://doi.org/10.1007/s10637-010-9428-0

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  • DOI: https://doi.org/10.1007/s10637-010-9428-0

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