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.

Adoptive immunotherapy using interleukin-2 (IL-2) based therapy can result in marked tumor regression in some patients with metastatic renal cell carcinoma. DNA flow cytometry has not been previously studied as a predictor of outcome of this therapy. Archival paraffin embedded tumors were studied in 23 IL-2 treated patients with metastatic renal cell carcinoma. Eleven patients were complete responders (CR) and 12 were nonresponders (NR). In the CR group, 4/11 (40%) were diploid and 7/11 (60%) were aneuploid. In the NR group, 9/12 (75%) were diploid and 3/12 (25%) were aneuploid. Although there was a trend that patients with an aneuploid DNA pattern were more likely to undergo a complete response, ploidy pattern alone was not significantly predictive of response (p2 = 0.10, Fischer's exact test). When combining ploidy pattern with other variables that were predictive for complete response, such as good performance status and a higher pretreatment weight, prediction of complete response was not improved by including ploidy. This preliminary report suggests that DNA ploidy does not appear to provide any additional information concerning responsiveness to IL-2 based immunotherapy beyond that obtained by performance status and pretreatment weight in this patient population.