Purpose: Enzastaurin is an oral serine/threonine kinase inhibitor that inhibits the beta isoform of protein kinase C and which may have therapeutic activity in prostate cancer.
We explored the efficacy of docetaxel/prednisone with or without enzastaurin in patients with castration-resistant metastatic prostate cancer.
Methods: A nonrandomized safety cohort consisting of 14 patients was followed by a double-blind randomized Phase II trial. Patients received standard doses of docetaxel (75 mg/m2) with prednisone 10 mg daily with or without 500 mg/day of enzastaurin.
Results: There was no difference in the objective response rate between the enzastaurin and placebo arms (placebo: 7 [15.2 %]; enzastaurin: 6 [15.0 %]; P = 1.00). The median PFS was 229 days for patients in the enzastaurin arm versus 213 days for the placebo arm (P = 0.524). The 1-year overall survival rates were almost identical, with 76.7 % and 75.1 % in the enzastaurin and placebo arms, respectively. Therapy was well tolerated although the combination of enzastaurin and docetaxel was more myelosuppressive than with docetaxel alone.
Conclusions: The clinical activity of docetaxel/prednisone plus enzastaurin cannot be distinguished from docetaxel/prednisone alone, given the limitations of a randomized Phase II design. Although the toxicity profile was favorable for the enzastaurin-containing regimen, there is no compelling rationale to move this combination forward for the treatment of castration-resistant metastatic prostate cancer.
Written by:
Dreicer R, Garcia J, Rini B, Vogelzang N, Srinivas S, Somer B, Shi P, Kania M, Raghavan D. Are you the author?
Department of Solid Tumor Oncology, Cleveland Clinic, Taussig Cancer Institute, 9500 Euclid Ave R35, Cleveland, OH, 44195, USA.
Reference: Invest New Drugs. 2013 Feb 24. Epub ahead of print.
doi: 10.1007/s10637-013-9940-0
PubMed Abstract
PMID: 23435622
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