MAXIMAL ANDROGEN BLOCKADE IN COMBINATION WITH METHOTREXATE FOR TREATMENT OF METASTATIC PROSTATE-CANCER

Recently attention has been focused on the optimal timing of chemother apy within the treatment regimen for patients with metastatic prostate cancer, i.e., hormonal manipulation, preferably maximal androgen bloc kage (MAB) consisting of chemical/surgical castration followed by trea tment with antiandrogens. We have conducted a randomized prospective c linical trial, investigating the efficacy and toxicity of MAB (orchiec tomy followed by flutamide therapy) alone as compared to MAB combined with methotrexate (MTX, 50 mg/m(2)/week) in 53 patients with newly dia gnosed stage IV (M1) prostatic cancer (UICC TNM Classification 1987). The observed remission rates (complete + partial) of 42.3% in the MAB + MTX arm and 29.6% in the MAB arm did not differ significantly. The r esponse rates (complete + partial + stable disease) of 73.1% and 66.7% ;, for MAB + MTX and MAB, respectively, also showed no significant dif ference. Neither progression-free survival (median: 18.5 and 23.8 mont hs for MAB + MTX and MAB, respectively) nor overall survival (median: 37.4 and 36.1) months in the MAB + MTX and MAB arm, respectively) coul d be improved by the addition of MTX to MAB. Only the extent of metast atic pain reported by the patients was consistently less under MAB + M TX than under MAB alone (P <0.1). Both treatment regimens were well-to lerated with slightly more undesirable effects in the MAB + MTX arm. O ur results do not provide evidence for the achievement of marked gains by combining chemotherapy with endocrine therapy in newly diagnosed p atients with stage IV (M1) prostate cancer.