Antitumor activity of platinum analogs against human lung cancer cell lines and tumor specimens

Antitumor activities of five platinum analogs, including cisplatin, carboplatin, 254-S, DWA2114R, and NK121, were compared using five human lung cancer cell lines and 19 tumor specimens obtained from lung cancer patients. The antitumor activity was evaluated by determining the ratio of the maximum tolerated dose of each drug to the 70% tumor growth inhibitory concentration in a colony assay. Cisplatin was the most potent agent, followed by 254-S and carboplatin. DWA2114R and NK121 were less potent than cisplatin and 254-S. Cross-resistance to adriamycin was also investigated using an adriamycin-resistant small cell lung cancer subline, SBC -3/ADM30. SBC-3/ADM30 was 1.7- to 4.0-fold more resistant to cisplatin, carboplatin, NK121, and DWA2114R, than was the parent line, SBC-3, and the subline was 2.0-fold more sensitive to 254-S. Using SBC-3, in vitro combination effects of etoposide and cisplatin, carboplatin, or 254-S were evaluated by the median-effect principle. Synergism was noted when cisplatin and etoposide were combined at a fixed molar ratio of 1:1. Combination of carboplatin and etoposide showed an additive effect. The combination of 254-S and etoposide was antagonistic at low concentrations, but was markedly synergistic at higher concentrations. These data suggested the efficacy of 254-S in the treatment of lung cancer.