COMBINED CHRONOCHEMOTHERAPY OF L1210 LEUKEMIC MICE USING 1-BETA-D-ARABINOFURANOSYLCYTOSINE, CYCLOPHOSPHAMIDE, VINCRISTINE, METHYLPREDNISOLONE AND CIS-DIAMMINEDICHLOROPLATINUM

  • 1 January 1980
    • journal article
    • research article
    • Vol. 7  (1) , 33-40
Abstract
When cyclophosphamide, 1-.beta.-D-arabinofuranosylcytosine, vincristine, methylprednisolone (P) and cis-diamminedichloroplatinum (CP) were administered to mice previously given injections of 4.5 or 5 million [mouse] L1210 leukemia cells, the effectiveness of the 5-drug combination was influenced by the stage of the circadian system at the time of injection. By applying the chronological approach (timed treatment) in comparison with a homeostatic (time unqualified) approach, fewer deaths and less weight loss were found, probably as the result of lower drug toxicity. Despite a cure rate that ranged 24-48% as a function of CP timing in the 1st study, the overall acute drug toxicity (ranging 20-76%) was unacceptable as a treatment protocol. In a 2nd study, by lowering dosages of all drugs but still administering the drugs in a chronobiological manner, death due to acute drug toxicity was reduced to 0 while the percentage of cures ranged 44-88% in animals treated with P at different circadian stages. In both studies the homeostatic approach was unsatisfactory because of overwhelming drug toxicity.