An Open Protocol For The Compassionate Use of Thalidomide For Patients With Advanced Or Refractory Malignancies

Angiogenesis is a normal, physiological process in the growing embryo, wound healing and ovulation. Progressive recruitments of blood vessels to the tumor site are thought to result in a self perpetuating loop helping to drive the growth of tumors. This new vasculature also allows competent tumor cells to find access to the vascular system and facilitate distant spread of tumor cells. Neovascularization is apparently an absolute prerequisite for physical expansion of solid tumors to grow beyond the volume of about 1-2 mm in diameter. Several molecular and cellular mechanisms have been identified by which tumor parenchyma may exert its angiogenic effect on host endothelial cells. There is also evidence that endothelial cells themselves, like other stromal cells, may act reciprocally to alter the behavior of adjacent tumor cells in a paracrine or cell contact mediated fashion. There is now known to be a diverse family of angiogenic growth factors, foremost among them being basic FGF and VEGF. Several angiogenic peptide genes have been sequenced and cloned. The degree of vascularization has acquired importance as an independent prognostic indicator in various types of solid tumors. More recently, it has been noted that increased angiogenesis may also be an important feature in hematologic malignancies, e.g. leukemia.