Activity of ruboxyl, a nitroxyl derivative of daunorubicin, on experimental models of colorectal cancer metastases

We evaluated the activity of ruboxyl (Rbx), a nitroxyl analogue of daunorub icin (Dauno), in experimental models of hepatic metastases from colorectal carcinoma (CRC) and compared it with its parent compound and with 5-fluorou racil (5FU). In mice treated by intraperitoneal injections Rbx and 5FU prov ed more effective than Dauno: the Index of Inhibition of Metastases in comp arison with controls was 43% for Dauno, 70% for 5FU and 84% for Rbx. In BDI X rats implanted with the syngeneic cell line DHD K12/TRb, both Rbx and 5FU , administered as a continuous intravenous infusion for 7 days, reduced the development of liver metastases from a median of 23.8 +/- 2.16 for control s to 3.2 +/- 1.3 for 5FU and 1.0 +/- 1.4 for Rbx (p < 0.0001 versus control s for both treatments): the comparison of Rbx and 5FU showed a trend in fav our of this new anthracycline. Median survival was prolonged from 40.6 +/- 3.4 days in controls to 56.0 +/- 5.8 days with Rbx and 58.0 +/- 4.69 days w ith 5FU. Considering that in a phase I study Rbx showed only minor and mana geable toxic side effect, its activity in the clinical treatment of CRC met astases may deserve further attention.