An updated review of the clinical development of coumarin (1,2-benzopyrone) and 7-hydroxycoumarin

Abstract

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 Previously unpublished data concerning the survival of a population of patients with RCC, who were treated on a phase I trial of coumarin and cimetidine, are presented.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.

Treatment of Pancreatic Cancer Cells with Dicumarol Induces Cytotoxicity and Oxidative Stress

“…The estimates for the slopes by group are provided in the Table 1. For example, tumor volumes were significantly reduced from 500 Ϯ 401 mm 3 in the controls to 195 Ϯ 172 mm 3 in tumors that had a single injection of dicumarol 100 M (P Ͻ 0.001 versus controls, means Ϯ SD).…”

“…Coumarin, the parent molecule of dicumarol, and a variety of coumarin compounds have demonstrated numerous antitumor and antiproliferative effects. Coumarin compounds have been shown to inhibit proliferation of particular human malignant cell lines in vitro (3)(4)(5)(6)(7)(8), as well as affecting tumor activity against several in vivo tumor types (1, 9 -13). In clinical trials, these compounds have also been demonstrated to have some activity against prostate cancer, malignant melanoma, and metastatic renal cell carcinoma (14 -16).…”

Identification of the Cytochromes P450 That Catalyze Coumarin 3,4-Epoxidation and 3-Hydroxylation

“…Coumarin has also been used clinically at high dosages in humans in the treatment of high-protein lymphedemas (Jamal and Casley-Smith, 1989) and as an antineoplastic agent in the treatment of renal cell carcinoma (Marshall et al, 1994) and malignant melanoma (Marshall et al, 1989). Although reports of adverse effects in humans resulting from coumarin treatment are rare (Cox et al, 1989;Egan et al, 1990), administration of coumarin to rodents produces rat liver (Lake, 1984;Lake et al, 1989) and mouse lung toxicity (Born et al, 1998).…”

Nano TiO2: An Efficient Catalyst for the Synthesis of Biscoumarins in Aqueous Medium

“…Compounds with these ring system have diverse pharmaceutical activities such as antioxidant, antimicrobial, anticoagulant, anti-HIV, antithrombotic, antieancer, enzyme inhibitory, urease inhibitory and cytotoxicity [8][9][10][11][12][13][14][15][16] . A number of biscoumarins are useful as malignant melanoma, metastatic renal cell carcinoma and prostate cancer drugs [17][18][19] .…”