Literature DB >> 20369375

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 Dreicer1, Jorge Garcia, Maha Hussain, Brian Rini, Nicholas Vogelzang, Sandy Srinivas, Bradley Somer, Yan D Zhao, Marek Kania, Derek Raghavan.   

Abstract

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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Year:  2010        PMID: 20369375     DOI: 10.1007/s10637-010-9428-0

Source DB:  PubMed          Journal:  Invest New Drugs        ISSN: 0167-6997            Impact factor:   3.850


  22 in total

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  6 in total

Review 1.  The changing therapeutic landscape of castration-resistant prostate cancer.

Authors:  Timothy A Yap; Andrea Zivi; Aurelius Omlin; Johann S de Bono
Journal:  Nat Rev Clin Oncol       Date:  2011-08-09       Impact factor: 66.675

2.  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.

Authors:  Robert Dreicer; Jorge Garcia; Brian Rini; Nicholas Vogelzang; Sandy Srinivas; Bradley Somer; Peipei Shi; Marek Kania; Derek Raghavan
Journal:  Invest New Drugs       Date:  2013-02-24       Impact factor: 3.850

3.  A phase 1 and pharmacokinetic study of enzastaurin in pediatric patients with refractory primary central nervous system tumors: a pediatric brain tumor consortium study.

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4.  Enzastaurin inhibits ABCB1-mediated drug efflux independently of effects on protein kinase C signalling and the cellular p53 status.

Authors:  Martin Michaelis; Florian Rothweiler; Nadine Löschmann; Mohsen Sharifi; Taravat Ghafourian; Jindrich Cinatl
Journal:  Oncotarget       Date:  2015-07-10

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  6 in total

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