INHIBITION OF PROSTATE-CANCER GROWTH BY ESTRAMUSTINE AND ETOPOSIDE

Background. Metastatic prostate cancer that is refractory to hormone t herapy remains an incurable disease without effective therapy. The aut hors used the nuclear matrix, the RNA-protein network of the nucleus t hat plays an important role in DNA replication and gene expression, as a target for cancer chemotherapy. In preclinical models, estramustine and etoposide appeared to interact to inhibit the growth of the hormo ne-refractory prostate cancer cells. Methods. These agents were tested in a Phase II clinical trial of patients with metastatic hormone-refr actory prostate cancer. Estramustine, 15 mg/kg/day, and etoposide, 50 mg/M(2)/day, were administered orally in divided doses for 21 days eve ry 28 days. Therapy continued until evidence of disease progression. R esults. Fifty-two patients were enrolled in this trial and had a minim um of 40 weeks follow-up. In 20 patients with measurable soft tissue d isease, 3 patients demonstrated a complete response (15%) and 6 patien ts had a partial response (30%) for more than 2 months. Of 32 patients with disease limited to bone, 8 (25%) demonstrated improvement and 12 (38%) demonstrated stability in their bone scans. Overall, 13 men (25 %) demonstrated a decrease of at least 75%, and 28 men (54%) demonstra ted at least a 50% decrease in their pretreatment prostate specific an tigen levels. Conclusions. The combination of estramustine and etoposi de may be an active oral regimen in hormone-refractory prostate cancer .