Development of angiogenesis inhibition as therapy for prostate cancer

Angiogenesis is essential to prostate cancer progression. The first study o f antiangiogenic therapy in patients with locally advanced prostate cancer at The University of Texas M. D. Anderson Cancer Center showed that preoper ative treatment with a fumagillin analog was safe. Microvascular density co rrelated with Gleason score, but marked intertumoral and intratumoral chang es were observed. Clinical experience with thalidomide (Thalomid), which in hibits angiogenesis induced by both vascular endothelial growth factor and basic fibroblast growth factor, has included observation of "clinical impro vement" inpatients with androgen-independent prostate cancer and anecdotal responses in patients with metastatic disease refractory to chemotherapy. I n an effort to assess the in vivo effect of thalidomide in prostate carcino ma, we have initiated a study of neoadjuvant thalidomide treatment in patie nts with locally advanced prostate cancer that is to include serial ultraso nographic and pathologic evaluation, as well as serial collection of serum/ urine markers that may prove useful surrogate markers of antiangiogenic act ivity. We have also initiated a phase I/II trial of thalidomide, paclitaxel (Taxol) and estramustine (Emcyt) in patients with metastatic androgernz-in dependent prostate cancer-progressing after up to two courses of chemothera py.