Inhibition of prostate cancer growth by estramustine and etoposide

Background. Metastatic prostate cancer that is refractory to hormone therapy remains an incurable disease without effective therapy. The authors used the nuclear matrix, the RNA‐protein network of the nucleus that plays an important role in DNA replication and gene expression, as a target for cancer chemotherapy. In pre‐clinical models, estramustine and etoposide appeared to interact to inhibit the growth of the hormone‐refractory prostate cancer cells. Methods. These agents were tested in a Phase II clinical trial of patients with metastatic hormone‐refractory prostate cancer. Estramustine, 15 mg/kg/day, and etoposide, 50 mg/M²/day, were administered orally in divided doses for 21 days every 28 days. Therapy continued until evidence of disease progression. Results. Fifty‐two patients were enrolled in this trial and had a minimum of 40 weeks follow‐up. In 20 patients with measurable soft tissue disease, 3 patients demonstrated a complete response (15%) and 6 patients 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%) demonstrated at least a 50% decrease in their pretreatment prostate specific antigen levels. Conclusions. The combination of estramustine and etoposide may be an active oral regimen in hormone‐refractory prostate cancer. Cancer 1995;75:1920–6.