Cyclosporin A potentiation of VP-16: production of long-term survival in murine acute lymphatic leukemia

Our prior in vitro studies on the correction of multidrug resistance by cyclosporin A (CsA) prompted us to investigate the effect of CsA and VP-16 in vivo. CsA given simultaneously at 2 or 10 mg/kg with VP-16 to BDF/1 mice bearing parental drug-sensitive P388 or L1210 lymphatic leukemia produced a 100% increase in survival as compared with VP-16 treatment alone. CsA-containing regimens also promoted 60-day survival in a significant number of P388 or L1210 leukemia-bearing mice as compared with animals receiving VP-16 in the absence of CsA (P < 0.02 and P < 0.001, respectively). CsA enhancement of the survival of mice bearing these lymphatic leukemias is restricted to VP-16, since the addition of CsA to therapeutic agents such as vincristine, daunorubicin, methotrexate, or cisplatin had no effect on survival.