Combined low-dose flutamide plus finasteride vs low-dose flutamide monotherapy for recurrent prostate cancer: a comparative analysis of two phase II trials with a long-term follow-up.
OBJECTIVE
To compare the efficacy and tolerability of peripheral androgen blockade using combined low-dose flutamide plus finasteride vs low-dose flutamide monotherapy for treating biochemical relapse after the definitive management of prostate adenocarcinoma.


METHODS
Fifty-six men treated for biochemical relapse of prostate cancer were enrolled prospectively in a phase II trial at the Walter Reed Army Medical Center from 1997 to 2001. Thirty-six men were treated with flutamide (125 mg twice daily) and finasteride (5 mg twice daily), and 20 men received low-dose flutamide only after biochemical recurrence (prostate-specific antigen, PSA, level > or =0.4 ng/mL). Cox proportional hazards analyses were used to compare the risk of progression between the groups.


RESULTS
Patients on combined and monotherapy had a median follow-up of 54 and 43.5 months, respectively. Seven men (19%) in the combined arm remain in the study with no progression, while five (25%) on monotherapy continue and are progression-free. Men on combined therapy had a greater decrease in their PSA level (P = 0.002). Multivariate analysis showed that men on combined therapy had significantly less risk of progression than men on monotherapy (hazard ratio 0.21, 95% confidence interval 0.07-0.63, P = 0.005). There was no significant difference in the frequency of side-effects between the groups. Toxicities were reported to be mild.


CONCLUSIONS
Our analysis suggests the therapeutic value of low-dose flutamide alone or combined with finasteride as first-line agents in a possible graduated approach for treating PSA-only recurrent prostate cancer. Due to unwanted metabolic effects associated with traditional hormonal agents, phase III trials comparing both regimens with current therapies are warranted.
Bañez
Lionel L
LL
Division of Urologic Surgery and the Duke Prostate Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Blake
Gary W
GW
McLeod
David G
DG
Crawford
E David
ED
Moul
Judd W
JW
D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D004812:Epidemiologic Methods; D018120:Finasteride / Q000008:administration & dosage*; D005485:Flutamide / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D018120:Finasteride; D005485:Flutamide; D017430:Prostate-Specific Antigen