re benefits of combination therapy with flutamide in patients relapsing after castration

1
496 BRITISH JOURNAL OF UROLOGY is not stopped in any patient at the time of relapse. In fact, in order to further block adrenal androgen secretion, aminoglutethimide is always added at the dose of 250 mg every 8 hours in association with low dose hydrocortisone acetate (10 mg in the morning, 5mg in the afternoon and 5mg in the evening). Among the 6 patients who stopped therapy on their own, all 6 stopped for unknown reasons while the disease was progressing. We feel that adding Flutamide (in association with orchiectomy or an LHRH agonist) is the best choice of therapy for patients who relapse after orchiectomy or treatment with oestrogens or an LHRH agonist alone. Objective benefits are thus obtained in one third of patients with no significant side effect, while preserving a good quality of life. F. Labrie, Cen:re de Recherches en Endocrinologie Molkculaire, Le Centre Hospitalier de 1’UniversitC Laval, 2705, Boulevard Laurier, QuCbec, G1V 4G2, Canada. re Benefits of combination therapy with Flutamide in patients relapsing after castration. F. Labrie et al. Br. J. Urol., 61, 341-346, 1988. Letter to the Editor. The remarkable response rates reported by Labrie et al. using total androgen ablation for the treatment of new patients with advanced carcinoma of the prostate led to many prospective randomised studies, both in Europe and the United States, comparing single endocrine therapy with total androgen ablation. Although most of the studies have shown an initial improved response rate in the androgen ablation group, none has shown any response rates comparable to those reported by Labrie. At 2 years all of the studies so far reported have shown no difference in response or survival between patients treated with single therapy or total androgen ablation. Are we now beginning to see a series of reports of combination therapy with Flutamide in patients relapsing after castration which fail to confirm their reported benefits? In this study, using National Prostatic Cancer Project criteria, a 6.2% complete response rate, 9.67; partial response rate and 18.6%stable disease are reported. In addition to the responders, an improvement of pain and performance was ob- served in a further 30% in their study of 209 patients. Macfarlane and Tolley (1985) reported only 1 short-lived partial objective response in 14 patients with progressive prostatic cancer treated with Flutamide as second-line therapy. More recently, de Kernion er af. (1988), on behalf of the NPCP, reported a prospective randomised trial of patients whose disease had failed to respond or progressed after orchiectomy, who received either Emcyt or Flutamide. In the 97 patients randomised to Flutamide, only 1 partial response was seen; 26 patients had stable disease and 70 progressed. In addition, 18 had severe nausea and vomiting and 25 had severe anorexia. This contrasts with Labrie’s experience of gastro-intestinal side effects in only 8% of patients. Patients who fail initial endocrine therapy have few therapeutic options left. Unfortunately, be- cause of the conflicting results in these projects, further studies will have to be carried out to assess the role of Flutamide in hormone-unresponsive patients. Such time and money could be better spent in finding useful therapies for prostatic cancer. Rejerences de Kernion, 3. N., Murphy, G. P. and Priore, R. (1988). Comparison of Flutamide and Emcyt in hormone refractory metastatic prostatic cancer. Urology, 31, 312-317. Macfarlane, J. R. and Tolley, D. A. (1985). Flutamide therapy for advanced prostatic cancer: a phase I1 study. Br. J. Urol., Gordon Williams, MS, FRCS, Department of Urology, Hammersmith Hospital, London W 12 OHS 57,172-174.

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496 BRITISH JOURNAL OF UROLOGY

is not stopped in any patient at the time of relapse. In fact, in order to further block adrenal androgen secretion, aminoglutethimide is always added at the dose of 250 mg every 8 hours in association with low dose hydrocortisone acetate (10 mg in the morning, 5mg in the afternoon and 5mg in the evening). Among the 6 patients who stopped therapy on their own, all 6 stopped for unknown reasons while the disease was progressing.

We feel that adding Flutamide (in association with orchiectomy or an LHRH agonist) is the best choice of therapy for patients who relapse after orchiectomy or treatment with oestrogens or an LHRH agonist alone. Objective benefits are thus obtained in one third of patients with no significant side effect, while preserving a good quality of life.

F. Labrie, Cen:re de Recherches en Endocrinologie Molkculaire, Le Centre Hospitalier de 1’UniversitC Laval, 2705, Boulevard Laurier, QuCbec, G1V 4G2, Canada.

re Benefits of combination therapy with Flutamide in patients relapsing after castration. F. Labrie et al. Br. J . Urol., 61, 341-346, 1988.

Letter to the Editor. The remarkable response rates reported by Labrie et al. using total androgen ablation for the treatment of new patients with advanced carcinoma of the prostate led to many prospective randomised studies, both in Europe and the United States, comparing single endocrine therapy with total androgen ablation. Although most of the studies have shown an initial improved response rate in the androgen ablation group, none has shown any response rates comparable to those reported by Labrie. At 2 years all of the studies so far reported have shown no difference in response or survival between patients treated with single therapy or total androgen ablation. Are we now

beginning to see a series of reports of combination therapy with Flutamide in patients relapsing after castration which fail to confirm their reported benefits?

In this study, using National Prostatic Cancer Project criteria, a 6.2% complete response rate, 9.67; partial response rate and 18.6% stable disease are reported. In addition to the responders, an improvement of pain and performance was ob- served in a further 30% in their study of 209 patients. Macfarlane and Tolley (1985) reported only 1 short-lived partial objective response in 14 patients with progressive prostatic cancer treated with Flutamide as second-line therapy. More recently, de Kernion er af. (1988), on behalf of the NPCP, reported a prospective randomised trial of patients whose disease had failed to respond or progressed after orchiectomy, who received either Emcyt or Flutamide. In the 97 patients randomised to Flutamide, only 1 partial response was seen; 26 patients had stable disease and 70 progressed. In addition, 18 had severe nausea and vomiting and 25 had severe anorexia. This contrasts with Labrie’s experience of gastro-intestinal side effects in only 8% of patients.

Patients who fail initial endocrine therapy have few therapeutic options left. Unfortunately, be- cause of the conflicting results in these projects, further studies will have to be carried out to assess the role of Flutamide in hormone-unresponsive patients. Such time and money could be better spent in finding useful therapies for prostatic cancer.

Rejerences de Kernion, 3 . N., Murphy, G. P. and Priore, R. (1988).

Comparison of Flutamide and Emcyt in hormone refractory metastatic prostatic cancer. Urology, 31, 312-317.

Macfarlane, J. R. and Tolley, D. A. (1985). Flutamide therapy for advanced prostatic cancer: a phase I1 study. Br. J . Urol.,

Gordon Williams, MS, FRCS, Department of Urology, Hammersmith Hospital, London W 12 OHS

57,172-174.