Combined finasteride and flutamide therapy in men with advanced prostate cancer

• Published in: Urology (Ridgewood, N.J.) Vol. 48; no. 6; pp. 901 - 905
• Main Authors: Ornstein, David K., Rao, Ganesh S., Johnson, Brooke, Charlton, Elaine T., Andriole, Gerald L.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-12-1996; Elsevier Science
• Subjects: Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chemotherapy; Enzyme Inhibitors - administration & dosage; Finasteride - administration & dosage; Flutamide - administration & dosage; Humans; Male; Medical sciences; Middle Aged; Neoplasm Staging; Pharmacology. Drug treatments; Prostate-Specific Antigen - blood; Prostatic Neoplasms - blood; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Adenocarcinoma; Antineoplastic agent; Human; Drug combination; Urinary system disease; Finasteride; Prostate disease; Treatment efficiency; Antiandrogen; Malignant tumor; Azasteroid; Chemotherapy; Flutamide; Advanced stage; Male genital diseases; Prostate
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/S0090-4295(96)00315-9

To evaluate the efficacy of combined finasteride and flutamide therapy in men with advanced prostate cancer by determining (1 ) the short-term tolerability of finasteride monotherapy and its effect on serum prostate-specific antigen (PSA) and hormone (testosterone, dihydrotestosterone) levels, and (2) the effects of the addition of flutamide on tolerability and on serum PSA and hormone levels.
Thirteen hormone-naive men with advanced prostate cancer (4 with Stage D2, 1 with Stage D1, 1 with Stage DO, 7 with rising PSA levels after radical prostatectomy [n = 2]or definitive radiation therapy [n = 5]) were initially treated with 5 mg finasteride daily. Flutamide (250 mg three times a day) was added after serum PSA levels stabilized.
Finasteride alone (median 5 weeks) had no significant effect on serum PSA levels (
P>0.05). Combined finasteride and flutamide resulted in a mean 91% reduction in serum PSA levels, with 85% of men achieving a nadir serum PSA level of less than 4.0 ng/mL and 46% achieving undetectable levels (0.2 ng/mL or less). Finasteride alone had no significant effect on serum testosterone levels (
P>0.05) but did result in a mean 74% reduction in serum dihydrotestosterone levels. Combined finasteride and flutamide resulted in a mean 56% increase in serum testosterone levels but had no additional effect on serum dihydrotestosterone levels (
P>0.05). Side effects occurred in 85% (gynecomastia or breast tenderness in 62% [8 of 13]and diarrhea in 23% [3 of 13]) of men on combined therapy. Potency was preserved in 66%. Combined finasteride and flutamide therapy was withdrawn from 15% (2 of 13) because of flutamide-induced diarrhea and from 23% (3 of 13) because of disease progression. All remaining patients (8 of 13) have serum PSA levels below 4.0 ng/mL and 4 of these 8 have undetectable levels. These men have received combined finasteride and flutamide for a median 11 months (range 6 to 19).
Finasteride monotherapy is inadequate therapy for advanced prostate cancer, but combined finasteride and flutamide may be a reasonable alternative for men with advanced prostate cancer who refuse conventional hormone therapy.