Reduction of HLA-DR plus lymphocytes after treatment with enzastaurin in patients with metastatic thyroid cancer

Background: Cytotoxic anti-tumor agents like methotrexate or cyclophosphamide have been used in the treatment of autoimmune diseases although the exact mechanism of their immunomodulatory function is unclear. By contrast, molecularly targeted anti-tumor agents, such as the serine/threonine kinase inhibitor enzastaurin, have not been evaluated for treatments other than cancer. Methods: Blood was sampled from patients with metastatic thyroid cancer treated with enzastaurin followed by the combination treatment of enzastaurin and the anti-folate pemetrexed. During this sequential treatment, blood was drawn every 14 days to monitor changes in the lymphocyte population. Results: We observed that enzastaurin monotherapy reduced the number of HLA-DR-expressing lymphocytes. No signs of infection were observed in any patient. Conclusion: Our findings suggest an immunomodulatory effect of enzastaurin in addition to the anti-tumor effect. Copyright (C) 2008 S. Karger AG, Basel.