Vascular targeting therapies for treatment of malignant disease

A detailed and useful review of vascular destabilizing agents (VDA) and their tremendous potential when applied in combination with radiotherapy was recently published. It should be of note to the cancer community that alternatives to the compounds described by Siemann et al. are available. Arsenic trioxide (ATO) is inexpensive, readily available, provides similar biologic effects, and has been studied extensively in preclinical models and clinical trials. ATO belongs to the small-molecule VDA described by Siemann et al. that acts by tubulin depolymerization. Like some of the compounds described, ATO derives from a natural source, acts preferentially on mature tumor vasculature, and causes a rapid stasis of blood flow in the tumor core after its administration. Our group was the first to demonstrate the antitumor effect of ATO and the first to show that its antitumor effect is enhanced by radiotherapy under a fractionated schema and using an orthotopic tumor model. ATO has become the preferred salvage treatment for patients with acute promyelocytic leukemia and tolerated dosages have been established. The safety and efficacy of ATO is currently being evaluated in a Phase I multicenter, dose-escalation clinical trial in combination with radiotherapy for patients with newly diagnosed malignant glioma. What distinguishes ATO from the compounds described by Siemann et al. is that it is readily available from any of a number of nonproprietary sources (Sigma-Aldrich; St. Louis, MO) at minimal cost.