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.
University of Michigan Comprehensive Cancer Center, Division of Hematology/Oncology, University of Michigan School of Medicine, Ann Arbor, USA.
D C
DC
Smith
B G
BG
Redman
L E
LE
Flaherty
L
L
Li
M
M
Strawderman
K J
KJ
Pienta
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