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Several authors have demonstrated that coumarin (1,2-benzopyrone) in combination with cimetidine can produce objective antitumor responses in some patients with advanced renal cell carcinoma. The purpose of this report is to review the clinical development of coumarin, with or without cimetidine, with special reference to renal cell carcinoma (RCC). Previously unpublished data concerning the survival of a population of patients with RCC, who were treated on a phase I trial of coumarin and cimetidine, are presented. The rationale and study design of an active randomized, double-blinded, placebo-controlled trial of coumarin for RCC are discussed. A progress report is given for an ongoing phase I trial of oral 7-hydroxycoumarin, the major human metabolite of coumarin.

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The unavailability of effective treatment for metastatic hormone-refractory and clinically localized but pathologically unfavorable prostatic carcinoma warrants trial of new and promising treatments. Preliminary studies in patients with metastatic disease have shown (a) subjective but no objective responses to 100 mg coumarin and cimetidine daily; (b) objective responses in 3 of 40 patients treated with 3 g coumarin daily, all of whom had normal performance status and 1 of whom remains with three resolved bone metastases and stable prostate-specific antigen levels after 4 years; (c) toxicity only in bedridden patients. We recently initiated two multi-center trials of 1 g coumarin daily. Metastatic prostatic carcinoma patients of normal performance status were treated in a phase II trial. Patients who had been treated by radical prostatectomy, but had surgical margin, seminal vesicle or lymph node involvement or detectable prostate-specific antigen after radical prostatectomy, were randomized to coumarin or placebo.