Effects of 2'-deoxycoformycin, 9-beta-D-arabinofuranosyladenine 5'-phosphate, and 1-beta-D-arabinofuranosylcytosine triple combination therapy on intracerebral leukemia 1210.
The triple combination of 2'-deoxycoformycin (2'-dCF), 9-beta-D-arabinofuranosyladenine 5'-phosphate, and 9-beta-D-arabinofuranosylcytosine was found to be very effective in the therapy of C57BL X DBA/2 F1 mice with intracerebral L1210. At the dosages and dosage scheduling used, the double combination of 2'-dCF and 9-beta-D-arabinofuranosyladenine 5'-phosphate gave minimal but significant increases in life-span. When 9-beta-D-arabinofuranosylcytosine was given at suboptimal dosage to mice with intracerebral L1210, the host toxicity caused by 2'-dCF and 9-beta-D-arabinofuranosyladenine 5'-phosphate in combination was decreased by a factor of 2, allowing a more prolonged therapy. "Cures" were obtained with the triple combination at dosages of 9-beta-D-arabinofuranosylcytosine that did not "cure". The supernatant adenosine deaminase from C57BL X DBA/2 F1 mouse brains was purified and the Ki for 2'-dCF using 9-beta-D-arabinofuranosyladenine as substrate was determined to be not more than 2 X 10(-11) M.
D000243:Adenosine Deaminase / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001381:Azepines / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D001932:Brain Neoplasms / Q000188:drug therapy*; D003561:Cytarabine / Q000009:adverse effects / Q000627:therapeutic use*; D003854:Deoxyribonucleotides / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D008811:Mice, Inbred DBA; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D058892:Adenosine Deaminase Inhibitors; D000970:Antineoplastic Agents; D001381:Azepines; D003854:Deoxyribonucleotides; D003561:Cytarabine; D000243:Adenosine Deaminase; D014740:Vidarabine