The effects of 5-fluorodeoxycytidine, 5-fluorodeoxyuridine, and related compounds on transplanted mouse leukemias.

The anti-tumor activity of the fluorinated uracil derivatives, 5-fluorouracil (FU), 5-fluorouridine (FUR), 5-fluorodeoxyuridine (FUDR), and 5fluoroorotic acid (FO), prepared by Duschinsky, Pleven, Malbica, and Heidelberger (9) 1 have been demonstrated in mice and rats by Heidelberger et al. (11-13). These results have been confirmed and extended by Law (14), Liebling and Humphreys (15), and our own group (3). McIver et al. (16) and Curreri et al. (7) have reported objective evidence of regression of carcinomas in patients following intravenous injection of 5fluorouracil. Since these results were usually accomplished only with considerable toxic manifestations, it was hoped that other fluorinated pyrimidines might be less toxic for the same degree of therapeutic activity. Heidelberger et al. (13) reported that 5-fluorocytosine (FC) at doses of ~5 or 85 mg/kg/day was without effect against the Flexner-Jobling carcinoma in rats, the Ehrlich ascites tumor, and Sarcoma 180 in mice, and Law (14) reported it ineffective on mouse leukemia. Schnitzer and Grunberg et al3 have noted no anti-tumor effects in Sarcoma 180, even at doses as high as 500 mg/kg daily. Fox, Wempen, and Duschinsky (10) have recently synthesized 5-fluorocytidine (FCR) and 5-fluorodeoxycytidine (FCDR) (Chart 1). These compounds have been studied for their effect against a spectrum of