Oral estramustine phosphate and oral etoposide for the treatment of hormone-refractory prostate cancer

Background: The purpose of the present study was to evaluate the antitumor activity and toxicity of oral estramustine phosphate (EMP) in combination w ith oral etoposide in patients with hormone-refractory prostate cancer. Methods: Twenty patients with adenocarcinoma of the prostate that progresse d after one or more regimens of androgen-deprivation therapy were enrolled into this trial. Oral EMP was administered twice daily, for a total daily d ose of 560 mg, and oral etoposide (50 mg/bodyweight per day) was given on d ays 1-21 and was stopped on days 22-35. Treatment was continued until evide nce of disease progression appeared or two consecutive rises in the prostat e-specific antigen (PSA) value were observed. Results: Ten of 20 patients showed a decrease of 50% or greater in the PSA value from initially elevated PSA levels after therapy. The median progress ion-free duration and 2 year cause-specific survival rate of these 10 patie nts were 208 days (range 71-693 days) and 67.5%, respectively. There were n o significant differences in age, pretreatment PSA value, duration from ini tial treatment to relapse, prior therapy or survival between patients who h ad a decrease of 50% or greater in PSA values after this combination therap y and those who did not. The main toxicities (greater than or equal to grad e 2) were anemia, leukocytopenia, thrombocytopenia, gastrointestinal and he patic disorders, which occurred in 40, 15, 10, 15 and 5% of patients, respe ctively. Conclusions: The combination of oral EMP and etoposide is considered to be a well-tolerated outpatient treatment regimen for patients with hormone-ref ractory prostate cancer and the therapy deserves further investigation.