A phase II trial of oral diethylstilbesterol as a second-line hormonal agent in advanced prostate cancer.
OBJECTIVE
To test the use of 1 mg/day of oral diethylstilbesterol (DES) as a treatment for patients with advanced prostate cancer who had failed primary hormonal therapy. Approximately 40,000 men this year will experience first-line hormonal therapy failure for their metastatic prostate cancer. At this time there is no standard therapy for men whose first-line hormonal manipulation has failed. This clinical problem has been exacerbated by the use of prostate-specific antigen (PSA) as a proved biomarker to follow disease progression. Patients who are experiencing hormonal therapy failure now present with a rising PSA, and virtually all are asymptomatic. The dilemma of how to treat these patients represents a new clinical problem for the medical oncologist and urologist that needs to be answered.


METHODS
We conducted a Phase II trial of oral DES in 21 patients. Patients were followed for response by PSA criteria and toxicity. A decrease in two serial measurements of PSA of greater than 50% from baseline was judged to be a partial response.


RESULTS
Nine of 21 patients achieved a PSA response (43% response rate with 95% confidence intervals of 22% to 64%) leading to early cessation of this Phase II trial. Eight of 13 patients (62%) who had only one prior hormone manipulation that failed demonstrated a PSA response, whereas only 1 of 8 patients (13%) who had received two or more hormone treatments responded (P = 0.07). The median follow-up is 82 weeks (range 8 to 122) among 16 surviving patients. The survival rate at 2 years is 63% (95% confidence interval 41% to 99%).


CONCLUSIONS
DES appears to be an active agent for second-line hormone therapy for metastatic prostate cancer. Because it has been taken off the market for economic reasons, DES should be considered for development under the orphan drug strategy.
Smith
D C
DC
University of Michigan Comprehensive Cancer Center, Division of Hematology/Oncology, University of Michigan School of Medicine, Ann Arbor, USA.
Redman
B G
BG
Flaherty
L E
LE
Li
L
L
Strawderman
M
M
Pienta
K J
KJ
D000284:Administration, Oral; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D004054:Diethylstilbestrol / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
D018931:Antineoplastic Agents, Hormonal; D004054:Diethylstilbestrol