title: Schedule-dependency assessments of ribonucleoside diphosphate reductase inhibitors when used in combination with platinum compounds plus cyclophosphamide in the treatment of advanced L1210 leukemia.
abstract: Each of three ribonucleoside diphosphate reductase inhibitors was used as a third drug in combination with selected antitumor platinum (Pt) agents and cyclophosphamide (CY) in the treatment of advanced L1210 leukemia in C57BL/6 x DBA/2 mice. Each was synergistic with the various Pt plus CY combinations but the effect was highly schedule dependent. The collective cure rate was 68% when hydroxyurea (HU) was given as a single injection with Pt plus CY; the cure rate was 15% when HU was administered on a divided-dose schedule with Pt plus CY. The collective cure rate was 53% when guanazole was given as a single injection with Pt plus CY, but was only 8% when it was given on a divided-dose schedule with Pt plus CY. The effect of 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone, when used as a third drug with the various Pt plus CY regimens, was not schedule dependent as assessed by the collective cure rate. A therapeutic synergy between CY and each of the three ribonucleoside diphosphate reductase inhibitors was also observed.
mesh_terms: D000818:Animals; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006144:Guanazole / Q000627:therapeutic use; D006918:Hydroxyurea / Q000627:therapeutic use; D007546:Isoquinolines / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D010984:Platinum / Q000627:therapeutic use*; D012262:Ribonucleoside Diphosphate Reductase / Q000037:antagonists & inhibitors*; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D013882:Thiosemicarbazones / Q000627:therapeutic use
chemical_list: D007546:Isoquinolines; D013882:Thiosemicarbazones; D010984:Platinum; C013118:4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone; D003520:Cyclophosphamide; D012264:Ribonucleotide Reductases; D012262:Ribonucleoside Diphosphate Reductase; D006144:Guanazole; D006918:Hydroxyurea