CYTOTOXIC EFFECTS OF TENIPOSIDE COMBINED WITH CIS-DIAMMINE-DICHLOROPLATINUM (II) ON THE IN VITRO LEWIS LUNG CARCINOMA MODEL: INFLUENCE OF THE TREATMENT SCHEDULE

The interactions between cis-diammine-dichloroplatinum (CDDP) and teniposide (VM26) have been studied in vitro on a Lewis lung carcinoma culture in terms of span, order of exposure or time delay between both drugs. When the cells were simultaneously exposed to VM26 and CDDP for 24 h, a supra-additive effect was observed (P less than 0.001). When the cells were first incubated with VM26, the cytotoxicity was emphasized (P less than 0.02), whereas after a prior exposure to CDDP, only an additive effect was noticed. For a short exposure to the drugs (1 h), we noticed an enhancement of the cytotoxic effect when the cells were first exposed to VM26, principally when the time delay between epipodophyllotoxin and CDDP was 0 or 1 h (P less than 0.001). The sequence in which VM26 was given before CDDP induced a significant increase of the cytotoxic effect, whatever the span of exposure.