A randomized, double-blind, placebo-controlled, Phase II study with and without enzastaurin in combination with docetaxel-based chemotherapy in patients with castration-resistant metastatic prostate cancer
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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.
KeywordsProstate cancer Enzastaurin Prostate-specific antigen Docetaxel
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 for writing and editorial assistance
Conflict of interest
Peipei Shi, PhD and Marek Kania, MD are employees of Eli Lilly. Robert Dreicer, MD has been a consultant to Eli Lilly. Drs. Garcia, Rini, Vogelzang, Srinivas, Somer, and Raghavan have no conflict to declare.
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