Activity of enzastaurin in treatment of advanced and high-risk prostate cancer


Enzastaurin is an investigational drug being developed by Eli Lilly. Its potential is being assessed in a number of different cancers, and one of those is prostate cancer.

Dreicer et al. have just published data from a two groups (“cohorts”) of patients who were given enzastaurin in a Phase II clinical trial:

  • Patients in cohort 1 all had non-metastatic but castrate-resistant prostate cancer (CRPC) and a rising PSA.
  • Patients in cohort 2 all had metastatic CRPC and disease progression after treatment with docetaxel-based chemotherapy.

The two cohorts of patients were treated simultaneously, and all patients received a 500 mg dose of enzastaurin every day.

The results of the trial are given as follows:

  • 1 patient in cohort 1 had a “complete” response but enzastaurin demonstrated limited activity in the majority of patients in this cohort.
  • No objective responses were observed in any patients in cohort 2.
  • Median progression-free survival (PFS) in cohort 2 was 11 weeks, which was similar to the rates of PFS seen in historical controls.
  • Enzastaurin was well tolerated in both cohorts of patients.

It would appear that enzastaurin as a single agent has little to no clinically significant activity in patients with CRPC. However, research is continuing to see whether enzastaurin may have value when combined with docetaxel to treat men with CRPC. This trial is fully enrolled and results may be available later this year.

Enzastaurin is also being investigated in combination with bicalutamide as a treatment for men with high-risk prostate cancer after first-line therapy. A new, multicenter clinical trial exploring this specific possibility will start to enroll about 100 patients in the near future.

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