Development of Angiogenesis Inhibition as Therapy for Prostate Cancer

ABSTRACT: Angiogenesis is essential to prostate cancer progression. Thefirst study of antiangiogenic therapy in patients with locally advanced prostatecancer at The University of Texas M. D. Anderson Cancer Center showed thatpreoperative treatment with a fumagillin analog was safe. Microvascular densitycorrelated with Gleason score, but marked intertumoral and intratumoral changeswere observed. Clinical experience with thalido-mide (Thalomid), which inhibitsangiogenesis induced by both vascular endothelial growth factor and basicfibroblast growth factor, has included observation of "clinicalimprovement" in patients with androgen-independent prostate cancer andanecdotal responses in patients with metastatic disease refractory tochemotherapy. In an effort to assess the in vivo effect of thalidomide inprostate carcinoma, we have initiated a study of neoadjuvant thalidomidetreatment in patients with locally advanced prostate cancer that is to includeserial ultrasonographic and pathologic evaluation, as well as serial collectionof serum/urine markers that may prove useful surrogate markers of antiangiogenicactivity. We have also initiated a phase I/II trial of thalidomide, paclitaxel(Taxol), and estramustine (Emcyt) in patients with metastaticandrogen-independent prostate cancer progressing after up to two courses ofchemotherapy. [ONCOLOGY14(Suppl 13):21-23, 2000]

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