TREATMENT OF HORMONE-REFRACTORY STAGE-D CARCINOMA OF PROSTATE WITH COUMARIN (1,2-BENZOPYRONE) AND CIMETIDINE - A PILOT-STUDY

The combination of coumarin (1,2‐benzopyrone) and cimetidine has been reported to render objective tumor regressions among patients with metastatic renal cell carcinoma and malignant melanoma. Subsequently, a pilot trial was conducted to evaluate this regimen for the treatment of stage D hormone‐refractory carcinoma of the prostate. Patients received coumarin 100 mg orally as a single daily dose for 14 days; on day 15 cimetidine 300 mg four times daily was added, and both drugs were continued until progression of disease. Fourteen patients with advanced prostate cancer were treated. Nine patients had evaluable disease only, whereas five patients had both measurable and evaluable disease. All patients had bone metastases. Although there was no objective evidence of tumor regression, three patients (with evaluable disease only) experienced significant improvement in bone pain with decreased analgesic use that persisted until disease progression at 3, 5.5 +, and 9 months. Although coumarin caused no symptomatic or organ dysfunction toxicity, one elderly patient experienced reversible mental confusion from cimetidine. Coumarin and cimetidine, at the dose and schedule described, are not effective for the treatment of advanced prostate cancer. However, the results of laboratory investigations suggest that further clinical trials of coumarin, at higher doses, may be warranted for the treatment of this disease. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company