Comparison of cyclosporin A, verapamil, PSC-833 and cremophor EL as enhancing agents of VP-16 in murine lymphoid leukemias.
Although verapamil, cyclosporin A. cremophor EL and PSC-833 are active as multidrug resistance modulators, there has been limited study of these compounds as possible chemotherapy enhancing agents against drug-sensitive tumors. We compared these agents as modifiers of VP-16 cytotoxicity in vitro and modifiers of VP-16 efficacy in vivo against drug-sensitive P388 and L1210 leukemias. Our study indicates that cyclosporin A enhances VP-16 cytotoxicity to a significantly greater extent than equimolar concentrations of verapamil or PSC-833. Although cremophor EL shows significantly greater activity than verapamil in VP-16 cytotoxicity enhancement in vitro, it is ineffective when added to VP-16 therapy of mice bearing L1210 leukemia.
Slater
L
L
Department of Medicine, University of California, Irvine 92717, USA.
Sweet
P
P
Wetzel
M
M
Stupecky
M
M
Osann
K
K
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage*; D003524:Cyclosporins / Q000008:administration & dosage*; D004357:Drug Synergism; D005047:Etoposide / Q000008:administration & dosage*; D005990:Glycerol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007939:Leukemia L1210; D007941:Leukemia P388; D051379:Mice; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000008:administration & dosage*
D003524:Cyclosporins; C000515:cremophor EL; D005047:Etoposide; D016572:Cyclosporine; D014700:Verapamil; D005990:Glycerol; C070272:valspodar