Stage d3 prostatic cancer treatment with oral estramustine phosphate and etoposide

Prostate cancer is the second most common neoplasia in men. It is hormone-responsive for 10-24 months from diagnosis and when it becomes hormone-refractory the median survival is 11 months. Estramustine phosphate (EMP) and etoposide (VP-16) have a well documented synergic interaction in stage D3 prostate cancer, both causing a mitotic arrest of cell replication in the metaphase. Both drugs can be administered orally. From November 1994 to June 1997, 42 patients with stage D3 prostate cancer (mean age 67.8 yrs), 15 with measurable disease and the others with positive bone scan, were entered in a multicentric, non-randomized, phase II study, during which 560 mg of EMP and 100 mg of VP-16 were administered daily for 14 days, followed by 14 days without medicaments; the cycle was resumed if WBC > 2000/mmc and PLT > 100,000/mmc. Every 3 cycles pts. were evaluated for response and toxicity and continued on therapy only if they were classified responders (complete or partial remission) or with stability, judged upon NPCP criteria. Out of 36 evaluable pts. complete remission (CR) was observed in 1 pt, partial remission (PR) in 10 pts (responders = 11/36, 30%) and stability of disease in 17/36 (47%); in 22.2% of cases (8/36 pts) there was progression of the disease. In pts. with measurable disease CR + PR were as high as 60%. Pain score was also assessed and it decreased in 61% of patients. Median survival is 28 months. PSA pretreatment levels were correlated with response to treatment: pts with PSA < 100 ng/ml in 44.4% of cases were responders and in 44.4% had stable disease. Moreover, when a PSA decrease > 75% of the starting levels was observed no pts. had progression (47.6% responders and 52.3% stable disease); among pts with a PSA decrease < 75%, the majority (53.3%) had progression. Toxicity was acceptable: no patient had grade 4 toxicity, according to National Cancer Institute's Common Toxicity Criteria. Most frequent side effects were alopecia and gastrointestinal toxicity (nausea and vomiting), the vast majority of grade 1 and 2. Very limited haematological toxicity. EMP + VP-16 is an active combination in stage D3 prostate cancer, with a good patient compliance and contained toxicity.