Expert Opin Investig Drugs. 2009 Jul;18(7):973-83.
Antiangiogenic (metronomic) chemotherapy for brain tumors: current and future perspectives.
Samuel DP, Wen PY, Kieran MW.
Medical School, Pediatric Medical Neuro-Oncology, Dana-Farber Cancer
Institute and Children's Hospital of Boston, Boston, MA 02115, USA.
advances in the diagnosis and treatment of brain tumors have been made
through better imaging, surgical techniques and advances in radiation
therapy. However, the cure rate for most adult and pediatric brain
tumor patients has not mirrored this success. Angiogenesis, the
development of neovascularization, provides the required nutrients and
oxygen to an expanding tumor and is controlled by a complex balance of
proangiogenic cytokines and antiangiogenic factors. A series of new
inhibitors of angiogenesis are now in clinical trials. Most of these
rely on inhibiting tumor cell-mediated cytokines or blocking the
activation of their cognate receptors. Cytotoxic chemotherapy, by
contrast, targets dividing cells but can be modulated to attack
dividing endothelial cells. This review will focus on the use of
low-dose antiangiogenic (also called metronomic) chemotherapy to
inhibit endothelial cell function and resultant neovascularization in
the treatment of adult and pediatric brain tumors. By examining the
biology and preclinical findings that led to the development of
antiangiogenic/metronomic chemotherapy, clinical studies have been
undertaken that support the role of this approach in the clinic, and
have led to the introduction of a number of markers being used to
better predict active combinations and appropriate patient populations.