The unavailability of effective treatment of metastatic
hormone refractory prostatic
carcinoma warrants trials of new and promising treatments.
Coumarin is an
investigational new drug that has produced objective
tumor regression in some patients with metastatic
renal cell carcinoma and
malignant melanoma.
Coumarin has shown activity against prostatic
carcinoma in the Dunning R-3327 rat prostatic
adenocarcinoma model. Forty-eight patients with metastatic
hormone naive (5 stage D1 and 10 stage D2) or
hormone refractory (33 stage D3) prostatic
carcinoma of average age 67.6 years (range 46-86) and ECOG performance status of 2 or better were given 3 grams
coumarin daily by mouth and evaluated monthly for toxicity and response by rigid criteria in a multicenter trial. Toxicity was limited to asymptomatic
SGOT elevations in 3 patients and
nausea and
vomiting in 4 patients that required cessation of
therapy in 2. Eligibility and protocol violations removed 6 additional patients from response evaluation. There were no complete responses. Partial responses (3 of 40 patients, 8%) occurred in 2 patients with bidimentionally measurable disease and 1 patient with disease evaluable by bone scan and elevated
prostate specific antigen and
prostatic acid phosphatase. The remaining patients progressed after 1 to 12 (average 4.4) months.
Coumarin is a relatively nontoxic
drug that may warrant further trials in a subset of patients with prostatic
carcinoma.