COMBINED HORMONO CHEMOTHERAPY AS PRIMARY-TREATMENT FOR METASTATIC PROSTATE-CANCER - A RANDOMIZED, MULTICENTER STUDY OF ORCHIECTOMY ALONE VERSUS ORCHIECTOMY PLUS ESTRAMUSTINE PHOSPHATE/

Objectives. Based on the theory that hormone-resistant cells are prese nt in all metastatic patients, early administration of chemotherapy ap pears to be logical and its use is supported by experimental studies. Therefore, trials with combined hormonal and cytotoxic treatment as pr imary therapy should be conducted. In the present trial, the efficacy and tolerance of estramustine phosphate (EMP) as a chemotherapeutic ag ent in addition to hormonal treatment (orchiectomy) was studied in pat ients with metastatic and nonmetastatic prostate cancer not previously treated. EMP was chosen because it produces few serious adverse react ions and no cumulative toxicity. Methods. Four hundred nineteen patien ts were included in a 1.5-year period starting in January 1989. Patien ts with locally advanced prostate cancer or with bone metastases were randomized to orchiectomy (O) or orchiectomy followed by EMP (O + E), given until progression. Results. Analysis of the total group showed n o significant difference in time to progression between the treatment groups. Because the course of the disease is different in patients wit h either T4 tumor only or with lymph node metastases only (MO) as comp ared with patients with bone metastases (M1) and because the number of progressions in the MO patients was low, corresponding analyses were performed for these subgroups as well. In the Mi patients, there was a tendency for a longer time to progression in the O + E group than in the O group, but there was no indication of a difference between the g roups with regard to survival. In the MO patients, there was no indica tion of any difference in results between the treatments. Multivariate analysis of prognostic factors showed pain, alkaline phosphatase, met astasis status, and tumor stage to be significant factors. There was a relation between age and drug treatment in that a significant benefic ial effect of EMP in terms of prolonged progression-free interval as w ell as survival was evident in younger patients (aged less than 73 yea rs) with metastatic disease. Tumor stage was also of importance for th e drug effect; T0 to T3 patients who received EMP survived longer than those who were treated with orchiectomy only. The most common adverse reaction was nausea in the O + E group, which led to discontinuation of the drug in 7 patients. Cardiovascular problems are not uncommon in this age group, and there was a higher incidence of cardiovascular ev ents, predominantly cardiac failure, in the O + E group, leading to tr eatment interruption in 16 patients. Conclusions. Our results indicate that future studies of hormono/chemotherapy should focus on younger p atients with bone metastases. (C) 1997, Elsevier Science Inc.