PHARMACOKINETIC CORRELATION BETWEEN EXPERIMENTAL AND CLINICAL EFFECTSON HUMAN NONSMALL CELL LUNG CANCERS OF CIS-DIAMMINEGLYCOLATOPLATINUM (254-S) AND CIS-DIAMMINEDICHLOROPLATINUM

We attempted to correlate the in vitro and in vivo antitumor activitie s of cis-diammineglycolatoplatinum (254-S), a novel platinum complex, and cis-diamminedichloro-platinum (CDDP) against the established cultu re cell lines and xenografts of human non-small cell lung cancel (NSCL C) with their clinical effects, based on the previous finding that the cytotoxicity of CDDP depends on the area under the curve (AUG). The c oncentration of 254-S and CDDP inhibiting the in vitro growth of 4 cul tured NSCLC lines by 50% (IC50) was 0.82-7.8 and 0.53-4.2 mu g/ml, res pectively, showing a similar level. Of the 4 cell lines, only the most sensitive line, RERF-LC-AI, showed an IC50 close to a specific concen tration (0.50 for 254-S and 0.32 mu g/ml for CDDP) that reproduces in vitro the clinical AUC(free) (24.8 and 5.34 mu g . hr/ml) of the respe ctive drugs. We treated 6 lines of human NSCLC xenografts implanted in nude mice with 254-S and CDDP at a particular close (13.2 and 3.7 mg/ kg) that is equivalent to the clinical doses with respect to the plasm a AUC(free) 254-S and CDDP exhibited significant antitumor effects on 2 and 1 of the 6 lines, respectively. These in vitro and in vivo findi ngs were considered to be relatively well correlated with the reported clinical response rates of 15-19% for 254-S and 14-15% for CDDP.