Summary
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.
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References
Chello PL, Sirotnak FM (1981) Increased schedule-dependent synergism of vindesine versus vincristine in combination with methotrexate against L1210 leukemia. Cancer Treat Rep 65:1049
Chello PL, Sirotnak FM, Dorick DM (1979) Different effects of vincristine on methotrexate uptake by L1210 cells and mouse intestinal epithelia in vitro and in vivo. Cancer Res 39:2106
Chello PL, Sirotnak FM, Dorick DM, Moccio DM (1979) Schedule-dependent synergism of methotrexate and vincristine against murine L1210 leukemia. Cancer Treat Rep 63:1889
Creasey WA (1975) Arabinosylcytosine. In: Sartorelli AC, Johns DG (eds) Antineoplastic and immunosuppressive agents, part II. Handbook of Experimental Pharmacology, vol 38. Springer, Heidelberg Berlin New York, pp 232–249
George P, Journey LJ, Goldstein MN (1965) Effect of vincristine on the fine structure of the HeLa cells during mitosis. J Natl Cancer Inst 35:355–361
Jardine I (1980) Podophyllotoxins. In: Anticancer agents based on natural product models. Academic Press, New York, pp 319–353
Sirotnak FM (1980) Correlates of folate analog transport, pharmacokinetics and selective antitumor action. Pharmacol Ther 8:71–103
Sirotnak FM, Donsbach RC, Dorick DM, Moccio DM (1976) Tissue pharmacokinetics, inhibition of DNA synthesis and tumor cell kill after high-dose methotrexate in murine tumor models. Cancer Res 36:4672–4678
Skipper HE, Schabel FM Jr, Wilcox LS (1967) Experimental evaluation of potential anticancer agents. XXI. Scheduling of arabinosylcytosine to take advantage of its S-phase specificity against leukemia cells. Cancer Chemother Rep 51:125–165
Wheeler GP, Bowdon BJ, Werline JA, Temple CG Jr (1981) 1-Deaza-7,8-dihydropteridines, a new class of mitotic inhibitors with anticancer activity. Biochem Pharmacol 30:2381–2384
Wheeler GP, Bowdon BJ, Werline JA, Adamason DJ, Temple CG Jr (1982) Inhibition of mitosis and anticancer activity against experimental neoplasms by ethyl 5-amino-1,2-dihydro-3-[(N-methylanilino)methyl]-pyrido[3,4-b]pyrazin-7-ylcarbamate-(NSC 181928). Cancer Res 42:791–798
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Sirotnak, F.M., Schmid, F.A., Temple, C. et al. Optimum scheduling during combination chemotherapy of murine leukemia. Cancer Chemother. Pharmacol. 11, 205–207 (1983). https://doi.org/10.1007/BF00254207
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DOI: https://doi.org/10.1007/BF00254207