title: Combination therapy with flutamide and castration (LHRH agonist or orchiectomy) in previously untreated patients with clinical stage D2 prostate cancer: today's therapy of choice.
abstract: One hundred and ninety-nine patients with clinical stage D2 prostate cancer who had not received previous endocrine therapy or chemotherapy were treated with the combination therapy using the pure antiandrogen Flutamide and the LHRH agonist [D-Trp6]LHRH ethylamide for an average of 26 months (3-59 months). The objective response to the treatment was assessed according to the criteria of the U.S. NPCP. There was a 5.7-fold increase (26.3 vs 4.6%) in the percentage of patients who achieved a complete response compared with the results obtained in five recent studies limited to removal (orchiectomy) or blockade (DES or Leuprolide) of testicular androgens. Only 12 of the 186 evaluable patients (6.5%) did not show an objective positive response at the start of the combination therapy compared with an average of 18% in the same five studies using monotherapy. The duration of response was also significantly improved in the patients who received the combination therapy while the death rate was decreased by approximately two-fold during the first 4 yr of treatment. In fact, while an approximately 50% death rate is observed at 2 yr in all studies using monotherapy, the same 50% death rate is delayed by 2 yr in the present study. It should be mentioned that at the time of relapse under combination therapy, the treatment is continued and, in addition, further blockade of adrenal androgen secretion is achieved with aminoglutethimide. The marked (5.7-fold) improvement in the rate of complete objective responses coupled with the three-fold decrease in the number of non-responders, the increased duration of the positive responses and the two-fold decrease in the death rate during the first 4 yr of treatment are obtained with the combination therapy using Flutamide and castration, thus improving the quality and duration of life with no or minimal side-effects. By blocking the androgen receptors in the prostatic cancer tissue, the antiandrogen decreases the action of the androgens of adrenal origin and thus inhibits the growth of a large number of tumors which, otherwise, would continue to be stimulated by the adrenal androgens left after medical or surgical castration.
authors.affiliation: Department of Molecular Endocrinology, Laval University Medical Center, Quebec, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Labrie
authors.forename: A
authors.initials: A
authors.lastname: Dupont
authors.forename: L
authors.initials: L
authors.lastname: Cusan
authors.forename: M
authors.initials: M
authors.lastname: Giguere
authors.forename: N
authors.initials: N
authors.lastname: Bergeron
authors.forename: J P
authors.initials: JP
authors.lastname: Borsanyi
authors.forename: Y
authors.initials: Y
authors.lastname: Lacourciere
authors.forename: A
authors.initials: A
authors.lastname: Belanger
authors.forename: J
authors.initials: J
authors.lastname: Emond
authors.forename: G
authors.initials: G
authors.lastname: Monfette
mesh_terms: D000368:Aged; D000813:Anilides / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005485:Flutamide / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D009919:Orchiectomy; D010146:Pain / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D017329:Triptorelin Pamoate / Q000031:analogs & derivatives*
chemical_list: D000813:Anilides; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; C019176:Tryptal; D005485:Flutamide