Major advantages of "early" administration of endocrine combination therapy in advanced prostate cancer

Combination therapy with the antiandrogen flutamide and the luteinizing hormone-releasing hormone (LHRH) agonist [D-Trp6, des-Gly-NH2(10)] LHRH ethylamide or orchiectomy was administered to 268 patients with previously untreated metastatic stage D2 prostate cancer for an average of 1,191 d (3.26 y). Only 17 of the 268 evaluable patients (6.5%) showed no objective positive response to the combination therapy assessed according to the National Prostatic Cancer Project objective criteria of response. The median duration of the disease-free response was 2.23 y and median overall survival was 3.58 y. The median survival for patients with only 1-5 bone metastases was not yet reached at 8 y, but for patients with 6-10 bone lesions, 11-40 bone lesions, and multiple bone metastases (superscan), median survival was markedly reduced to 3.56, 2.36, and 1.76 y, respectively. Analysis of patients according to general symptomatology, pain, and performance status showed median survivals of 5.47, 2.71, and 2.1 y for minimal, moderate, and severe symptoms, respectively. The present data demonstrate that administration of combination therapy to stage D2 prostate cancer patients having 1-5 bone metastases adds a minimum of 4.4 y of good quality life compared with patients whose disease is slightly more advanced. Our findings clearly demonstrate the major importance of starting combination therapy as soon as possible after diagnosis of metastatic prostatic cancer.