COMPARATIVE IN-VITRO AND IN-VIVO STUDY OF A NITROXYL DERIVATIVE OF 5-FLUOROURACIL (MAGNIZIL) ON HUMAN GASTROINTESTINAL TUMORS

Aims and background There is much interest in nitroxyl derivatives of cytotoxic agents. We evaluated the potential activity of magnizil, a d erivative of 5-fluorouracil, on human gastrointestinal tumors in 3 dif ferent in vitro and in vivo experimental models. Methods: The activiti es of magnizil and 5-fluorouracil were comparatively determined in vit ro on the HT29 cell line by a clonogenic assay and on tumor clinical s pecimens by an antimetabolic assay. The activity of both the drugs aga inst human tumors was also assessed in mice with the subrenal capsule assay. Results: A similar cytotoxic activity was found for magnizil an d 5-fluorouracil on the HT29 cell line. As regards human tumors, a low er activity was observed for the nitroxyl derivative than for 5-fluoro uracil, with response rates of 25% and 50%, respectively, at comparabl e concentrations. Moreover, among the tumors transplanted in the subre nal capsule of mice, two were sensitive to magnizil and 3 to 5-fluorou racil. Conclusions: Even though experimental results on human tumors i ndicate a somewhat lower activity for magnizil than the parent compoun d, its low toxicity and the possibility to clinically use high doses s uggest the opportunity to further investigate the potential of this ne w anticancer agent on larger series of colorectal cancers in experimen tal systems.