Experimental and Clinical Use of Fluorinated Pyrimidines in Cancer Chemotherapy.

fluorinated pyrimidines appeared in the scientific literature in 1962 alone, it is obvious that the scope of this review must be strictly limited. Therefore, it will be restricted to an account of the studies that have been carried out in human cancer patients, both experimental and for clinical evalua tion, except for a brief introduction that reviews the background of rationale, screening against rodent tumors, and metabolism and biochemical mechanisms of action necessary for an understand ing of the studies in man. In the introduction, the emphasis will be primarily on studies carried out in our laboratories. Reviews by the senior author on biochemical mechanisms of action have ap peared (38, 39). Aside from these, no reference will be made to reviews, clinical or otherwise ; only papers with experimental details or clinical proto cols adequate for evaluation will be included here. Following the initial observations by Rutman, Cantarow, and Paschkis (65), and further ampli fication from our laboratory (45), that uracil was utilized for nucleic acid biosynthesis to a greater extent in induced and transplanted rodent tumors than by most normal tissues, it became of interest to prepare an antimetabolite that would resemble uracil as closely as possible. Accordingly, 5fluorouracil was synthesized (20) in collaboration with Dr. Robert Duschinsky of Hoffmann-La Roche, Inc. (Chart 1), and preliminary data on antitumor activity and biochemical effects were