Preliminary results of a study showed patients with recurrent glioblastoma multiforme, a form of primary brain cancer, experienced a significant tumor response rate when treated with Enzastaurin.

" Recurring glioblastoma is a desperate disease for which there are very few adequate treatments, " said Howard Fine, at the National Cancer Institute and lead author of the study.

Radiation therapy is the most effective treatment of the glioblastoma following surgery.
Almost all patients receive some form of radiation therapy.
Gliomas are among the most angiogenic of all tumors, meaning the tumor has the ability to grow by drawing on blood from surrounding vessels at a very rapid rate.
The inhibition of tumor angiogensis may offer the potential as a highly effective form of therapy.

The Phase II study included 92 patients with recurrent glioblastoma who had failed more than one prior regimen of chemotherapy.

Patients' treatment consisted of an oral fixed dose of 500 mg of Enzastaurin, administered daily.
Treatment was allowed to continue indefinitely depending upon the patient's response to the drug.

Results showed that tumor shrinkage was evident in patients who received Enzastaurin, with a corresponding response rate of 20 - 25 percent.

The most common side effect was thrombocytopenia.

Enzastaurin stopped the flow of blood to patients' tumors, resulting in disruption of tumor growth and, in most cases, tumor shrinkage.

In addition to prohibiting angiogenesis of tumor cells, Enzastaurin inhibits the cell pathway signaling through the PKC-beta and Pl3 kinase/AKT pathways, two of the pathways that are vital to the survival of tumor cells.
These pathways are frequently activated in glioblastoma and because cancer cells don't follow the checks and balances seen in normal cells, the tumors grow unchecked.

Furthermore, tumor-induced angiogenesis requires activation of these pathways. Enzastaurin causes tumor cells to turn off those survival signals.
Enzastaurin has both direct tumor cell killing effects ( apoptosis ) and indirect, tumor-starving effects ( antiangiogensis ).

Source: 41st Annual Meeting of the American Society of Clinical Oncology ( ASCO ), 2005


XagenaMedicine2005