SCHEDULE-DEPENDENT SYNERGISM OF METHOTREXATE AND VINCRISTINE AGAINST MURINE L1210 LEUKEMIA

  • 1 January 1979
    • journal article
    • research article
    • Vol. 63  (11-1) , 1889-1894
Abstract
BD2F1 mice were inoculated with 106 L1210 murine lymphocytic leukemia cells and treated simultaneously with methotrexate and vincristine or with methotrexate followed by vincristine .gtoreq. 24 h later. Four to 6 doses of methotrexate, 48 mg/kg i.p., administered every 4 days beginning on day 1 resulted in a 168%-228% increase in lifespan; vincristine, at 0.5 mg/kg i.p. given on the same schedule until death (2 or 3 doses) gave only a 37% increase in lifespan. Simultaneous administration of both agents resulted in a therapeutic effect which was approximately additive. When vincristine was given 24 h or 24 and 72 h after the methotrexate, a further increase (70%-100%) in lifespan over that expected from an additive effect as well as long-term survivors (> 90 days) was obtained. Synergism between the 2 agents as well as long-term survivors was also seen with higher methotrexate concentrations (72 or 96 mg/kg) given in 4 or 5 courses. If therapy was initiated on day 2 when the peritoneal tumor burden was approximately 2 .times. 107 cells, the combination of methotrexate with delayed vincristine still resulted in an increased therapeutic effect over that obtained with either drug alone, or that expected on an additive basis.