PMID: 1182694Nov 1, 1975Paper

Schedule-dependent synergistic cytotoxicity of arabinofuranosylcytosine with adriamycin or 3,6-bis(5-chloro-2-piperidinyl)-2,5-piperazinedione in cultured cells.

Cancer Research
P N RaoJ A Gottlieb

Abstract

The purpose of this study was to demonstrate that in vitro cell culture systems could serve a useful purpose in providing some guidelines in formulating drug schedules for combination cancer chemotherapy in the clinic. Using monolayer cultures of Chinese hamster ovary cells as the test system, we screened the combinations of 1-beta-D-arabinofuranosylcytosine (ara-C) + adriamycin, ara-C + 3,6 - BIS(5 - CHloro - 2 - piperidinyl) - 2,5 - piperazinedione, melphalan + 5-fluorouracil, and melphalan + ara-C as to the effect of drug sequence on the plating efficiency of these cells. Schedule-dependent therapeutic synergism was observed only when ara-C treatment was followed by either adriamycin or 3,6-bis(5-chloro-2-piperidinyl)2,5-piperazinedione but not vice versa. No synergistic effects were observed in the combination of melphalan with 5-fluorouracil or ara-C. The basis for this synergism appeared to be that ara-C was primarily acting as a synchronizing agent to set up the cells in S phase so that subsequent treatment with an S-phase-specific drug, such as adriamycin or 3,6-bis(5-chloro-2-piperidinyl)-2,5-piperazinedione, would produce the maximum cell kill. On the other hand, the lack of synergism in the combinations of melphalan ...Continue Reading

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