Currently, there is a great deal of interest in drugs that target tumor vasculature and their therapeutic potential in combination regimens for the treatment of cancer. This review focuses on one of the vascular disrupting agents, 5-6-dimethylxanthenone 4-acetic acid (DMXAA), and the rationale for its combination with standard taxane-based chemotherapy. DMXAA and taxanes have different mechanisms of action and, in combination, demonstrate at least additive activity against preclinical solid tumors. Their clinical adverse-effect and pharmacologic profiles as single agents appear to render these agents suitable for use in combination. Phase I studies of DMXAA have identified a range of doses for combination clinical trials. In addition, the clinical indications and chemotherapy doses for combination clinical studies have been selected from positive randomized controlled trials of taxanes in advanced cancers. A phase II clinical trials program of combination studies with DMXAA is now underway; paclitaxel and carboplatin in patients with NSCLC and ovarian cancer and docetaxel in patients with hormone-refractory prostate cancer are being evaluated.
American Journal of Cancer – Springer Journals
Published: Aug 10, 2012