title: Maximal androgen blockade in combination with methotrexate for treatment of metastatic prostate cancer.
abstract: Recently attention has been focused on the optimal timing of chemotherapy within the treatment regimen for patients with metastatic prostate cancer, i.e., hormonal manipulation, preferably maximal androgen blockage (MAB) consisting of chemical/surgical castration followed by treatment with antiandrogens. We have conducted a randomized prospective clinical trial, investigating the efficacy and toxicity of MAB (orchiectomy followed by flutamide therapy) alone as compared to MAB combined with methotrexate (MTX, 50 mg/m2/week) in 53 patients with newly diagnosed 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 response rates (complete + partial + stable disease) of 73.1% and 66.7% for MAB + MTX and MAB respectively, also showed no significant difference. Neither progression-free survival (median 18/5 and 23.8 months for MAB + MTX and MAB, respectively) nor overall survival (median: 37.4 and 36.1) months in the MAB + MTX and MAB arm, respectively) could be improved by the addition of MTX to MAB Only the extent of metastatic pain reported by the patients was consistently less under MAB + MTX than under MAB alone (P<0.1). Both treatment regimens were well- tolerated with slightly more undesirable effects in the MAB + MTX arm. Our results do not provide evidence for the achievement of marked gains by combining chemotherapy with endocrine therapy in newly diagnosed patients with stage IV (M1) prostate cancer.
authors.affiliation: Department of Medicine and Oncology, Wilhelminenspital, Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Sagaster
authors.forename: J
authors.initials: J
authors.lastname: Flamm
authors.forename: M
authors.initials: M
authors.lastname: Micksche
authors.forename: E
authors.initials: E
authors.lastname: Fritz
authors.forename: G
authors.initials: G
authors.lastname: Donner
authors.forename: H
authors.initials: H
authors.lastname: Ludwig
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005485:Flutamide / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009919:Orchiectomy; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000628:therapy*
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D005485:Flutamide; D017430:Prostate-Specific Antigen; D008727:Methotrexate