Response of human colon and prostate tumor xenografts to (E)-2'-deoxy-2'-(fluoromethylene) cytidine, an inhibitor of ribonucleotide reductase.
Daily oral or intravenous administration of the ribonucleoside diphosphate reductase inhibitor, (E)-2'-deoxy-2'-(fluoromethylene)cytidine (MDL 101,731), to nude mice caused rapid regression of colon and prostate xenografts. Studies were performed to optimize dosing schedule and route of administration. MDL 101,731 was tested against colon (HT-29) and prostate (PC-3) xenografts using twice weekly oral and intravenous administration. PC-3 tumors regressed almost completely with doses of 20 mg/kg. HT-29 xenografts regressed during intravenous administration of 100 mg/kg MDL 101,731, whereas oral administration was less effective. Based on these data it seems that MDL 101,731 is effective when administered intravenously, twice weekly and is an excellent candidate for clinical development against solid tumors.
Bitonti
A J
AJ
Marion Merrell Dow Research Institute, Cincinnati, OH 45215, USA.
Bush
T L
TL
Lewis
M T
MT
Sunkara
P S
PS
D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D003841:Deoxycytidine; D012264:Ribonucleotide Reductases; C086432:tezacitabine