Combination therapy with flutamide and castration (orchiectomy or LHRH agonist): the minimal endocrine therapy in both untreated and previously treated patients with advanced prostate cancer.
One hundred fifty-four patients with clinical stage D2 prostate cancer with no previous endocrine therapy or chemotherapy received the combination therapy with the pure antiandrogen Flutamide and the LHRH agonist [D-Trp]LHRH ethylamide for an average of 22 months (3 to 49). The objective response to the treatment was assessed according to the criteria of the US NPCP. There was a 6.3-fold increase (29.2 versus 4.6%) in the percentage of patients who achieved a complete response as compared to the results achieved in 5 recent studies limited to removal (orchiectomy) or blockade (DES or Leuprolide) of testicular androgens. Only 4.5% of patients did not respond to the combination therapy as compared to an average of 18% by standard therapy. The duration of response is also significantly increased in the patients who received the combination therapy while the death rate was decreased by approximately 2-fold between 2 and 3 years of treatment. The marked (6.3-fold) improvement in the rate of complete objective responses coupled with the 4-fold decrease in the number of non responders, the increased duration of the positive responses and the 2-fold decrease in the death rate at 2 to 3 years of treatment are obtained with the combination therapy using Flutamide and castration with no or minimal secondary effects. In addition, two hundred nine patients with biopsy-proven stage D2 prostatic adenocarcinoma showing disease progression after orchiectomy, DES or an LHRH agonist used alone received the combination therapy with the pure antiandrogen Flutamide. In patients treated with DES, the estrogen was replaced by the LHRH agonist [D-Trp6]LHRH ethylamide. Objective response to therapy was also assessed according to the criteria of the US NPCP. Thirteen patients (6.2%) had a complete response to treatment while partial and stable responses were achieved in 20 (9.6%) and 39 (18.7%) patients, respectively, for a total objective response rate of 34.5%. The mean duration of response was 24 months. While, in the non responders, the median survival was 8.13 months with a 17% probability of survival at 2 years, the probability of survival of patients who showed partial and stable responses at 2 years was 87 and 67%, respectively. All patients who achieved a complete response are still alive. Considering the excellent tolerance coupled with an objective response observed in 34.5% of the patients, the combination therapy with Flutamide and castration (surgical or LHRH agonist) appears to be the treatment of choice for prostate cancer patients in relapse after standard endocrine therapy.
Labrie
F
F
Department of Molecular Endocrinology, Laval University Medical Center, Quebec, Canada.
Dupont
A
A
Giguère
M
M
Borsanyi
J P
JP
Lacourciere
Y
Y
Bélanger
A
A
Lachance
R
R
Emond
J
J
Monfette
G
G
D000230:Adenocarcinoma / Q000401:mortality / Q000628:therapy*; D000813:Anilides / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004054:Diethylstilbestrol / Q000627:therapeutic use; D005485:Flutamide / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000401:mortality / Q000628:therapy*; D013997:Time Factors
D000813:Anilides; D000970:Antineoplastic Agents; D007987:Gonadotropin-Releasing Hormone; D004054:Diethylstilbestrol; D005485:Flutamide