Optimum scheduling during combination chemotherapy of murine leukemia. Additional examples of schedule-dependent synergism between S-phase-specific antimetabolites and agents inducing mitotic or pre-mitotic (G2) arrest.
In an extension of our prior studies with methotrexate and vinca alkaloids, three additional drug combinations incorporating an S-phase-specific antimetabolite and an agent inducing blockade at mitosis or G2 were found to exhibit potent schedule-dependent synergism against the L1210 leukemia. Combinations employed include cytosine arabinoside with vindesine and methotrexate with teniposide (VM-26) or the -deaza-pteridine derivative, NSC 181,928. Synergism was observed following sequential administration (antimetabolite given 24 h before the second agent), but effects following simultaneous administration or sequential administration in the reverse order (antimetabolite given 24 h after the second agent) were only additive.
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008938:Mitosis / Q000187:drug effects*
D000964:Antimetabolites, Antineoplastic