The antiandrogen withdrawal syndrome. Experience in a large cohort of unselected patients with advanced prostate cancer.
BACKGROUND
Flutamide withdrawal has been reported to be therapeutically efficacious for patients with hormone-refractory prostate cancer, with a reported prostate specific antigen (PSA) response rate of 29%.


METHODS
to evaluate the results of flutamide withdrawal in a large group of unselected patients, the medical records of 107 consecutive patients with metastatic prostate cancer who developed progressive disease while receiving flutamide therapy were reviewed retrospectively. Flutamide withdrawal was undertaken at the time of disease progression.


RESULTS
Eighty-two patients were evaluable. Of these, three had a > 80% fall in PSA value, and another nine had a > 50% decrease, for a response proportion of 14.6% (95% confidence interval 7.8%-24.2%). The median response duration was 3.5 months (range, 1-12+ months). Eight of patients treated with combined androgen blockade at the time of diagnosis of metastatic disease had a response (14%), whereas 4/25 responses (16%) were noted in patients in whom flutamide was added later, at the time of first progression. When patients who responded were compared with patients who did not respond, there was not a significant difference in age, pretreatment PSA level, type of gonadal androgen deprivation, or the likelihood of prior combined androgen blockade versus late addition of flutamide. The duration of prior therapy with flutamide was longer in patients who responded (21.5 vs. 12.0 months).


CONCLUSIONS
These findings confirm the flutamide withdrawal phenomenon in a large group of unselected patients, although its frequency is not as high as previously reported. In contrast to earlier reports, whether patients have had initial hormonal therapy with combined androgen blockade or monotherapy does not appear to be predictive of the likelihood of response to antiandrogen withdrawal.
Small
E J
EJ
Department of Medicine, University of California, San Francisco, Mt Zion/UCSF Cancer Center 94115, USA.
Srinivas
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D018450:Disease Progression; D005485:Flutamide / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D012189:Retrospective Studies; D013375:Substance Withdrawal Syndrome; D016896:Treatment Outcome
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D005485:Flutamide; D017430:Prostate-Specific Antigen