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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.
- Source :
-
Investigational new drugs [Invest New Drugs] 2013 Aug; Vol. 31 (4), pp. 1044-50. Date of Electronic Publication: 2013 Feb 24. - Publication Year :
- 2013
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Abstract
- 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.<br />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/m(2)) with prednisone 10 mg daily with or without 500 mg/day of enzastaurin.<br />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.<br />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.
- Subjects :
- Aged
Aged, 80 and over
Docetaxel
Double-Blind Method
Humans
Indoles adverse effects
Kaplan-Meier Estimate
Male
Middle Aged
Placebos
Taxoids adverse effects
Treatment Outcome
Antineoplastic Agents therapeutic use
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Indoles therapeutic use
Prostatic Neoplasms, Castration-Resistant drug therapy
Taxoids therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1573-0646
- Volume :
- 31
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Investigational new drugs
- Publication Type :
- Academic Journal
- Accession number :
- 23435622
- Full Text :
- https://doi.org/10.1007/s10637-013-9940-0