"Enzastaurin May Slow Progression of Non-Hodgkin's Lymphoma: Presented at ASH"
By Mike Fillon
ATLANTA, GA -- December 13, 2005 -- Results from a phase 2 study show that enzastaurin HCl, an orally administered protein kinase C-beta (PKCbeta) inhibitor, slowed the progression of diffuse large B-cell lymphoma (DLBCL) in patients who received earlier chemotherapy treatments.
Senior investigator Margaret A. Shipp, MD, director, Dana-Farber/Harvard Cancer Center's Lymphoma Program, Boston, Massachusetts, presented the results here on December 10[th at the 47th Annual Meeting of the American Society of Hematology (ASH).
Enzastaurin inhibits PKC-beta, a protein that stimulates cell growth, and AKT/P13 pathways. Earlier studies by other investigators showed that overexpression of PKC-beta was identified as being linked to poor outcomes for patients with DLBCL. Enzastaurin was designed to target PKC-Beta.
Preclinical data indicate that enzastaurin might produce anti-angiogenesis, cells apoptosis, and reduce the cell's ability to reproduce and proliferate.
The phase 2 multicenter clinical trial evaluated 27 men and 28 women with DLBCL who had relapsed after treatment with 2 other therapies. The median age was 68 years. Forty-seven patients (85%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or less, and 28 patients had elevated lactate dehydrogenase levels.
Patients initially received an oral dose of 525 mg (capsules) of enzastaurin, amended to 500 mg (tablets), once daily, until disease progression or unacceptable toxicity occurred. One cycle of therapy lasted for 28 days.
All 55 enrolled patients received at least 1 dose of enzastaurin, and were included in the safety and efficacy analyses. Of these, 13 patients completed less than 1 cycle of therapy, which the researchers consider noteworthy because enzastaurin must be administered for 14 days to achieve therapeutic levels.
Results show that 22% of 55 study participants treated with enzastaurin were free of disease progression for 2 months. A quarter of those patients remained progression free, with continued responses of 1.5 years to more than 3 years in duration.
Overall, enzastaurin was well tolerated in this patient population and clinical results show that patients treated with enzastaurin experienced minimal adverse effects. Seven reports of grade 3 toxicity were reported in this trial and included fatigue, thrombocytopenia, headache, motor neuropathy, and edema. One patient experienced grade 4 hypomagnesemia.
Dr. Shipp said that use of enzastaurin in patients with DLBCL is important for 2 reasons: it represents a rational inhibitor of an identified target and, "Several patients with aggressive chemo-insensitive disease have had prolonged responses to this single, oral agent."
Enzastaurin is being evaluated in several studies, including an upcoming phase 3 trial, and in cancer of the colon, non-small-cell lung cancer, and mantle cell lymphoma.
Non-Hodgkin's lymphoma makes up more than 80% of lymphomas, and is the sixth most common malignancy in the United States. DLBCL makes up the largest portion of non-Hodgkin's lymphomas in adults. Of the nearly 500,000 Americans with lymphoma, 332,000 have this form.
Enzastaurin is being investigated by Eli Lilly Oncology.
[Presentation title: A Phase II Study of Enzastaurin, a Protein Kinase C-beta (PKCbeta) Inhibitor, in the Treatment of Relapsed Diffuse Large B-Cell Lymphoma (DLBCL). Session Type: Poster Session 92-I. Abstract 934]
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