IN-VITRO AND IN-VIVO EFFECTS OF CISPLATIN AND ETOPOSIDE IN COMBINATION ON SMALL-CELL LUNG-CANCER CELL-LINES

The effects of cisplatin (CDDP) and etoposide (ETP) in combination wer e evaluated in vitro and in vice using small cell lung cancer cell lin es. The combination effects in vitro were investigated using isobologr am analysis. Used together, CDDP and ETP showed a synergistic effect a gainst cell growth on only 1 cell line (SBC-3), additive effects on 6 (SBC-2, SBC-5, Lu130, Lu134AH, Lu135T and H69) and an antagonistic eff ect on 1 (SEC-I). In the in vivo experiment, nude mice were inoculated with SEC-1, SBC-3 and SBC-5 cells. Two or 5 mg/kg CDDP and 10 or 30 m g/kg ETP were administered intraperitoneally alone and simultaneously in combination to nude mice. The in vivo effects of the combination we re determined by comparing the observed growth ratio in mice treated w ith the combination with the expected value of this ratio calculated b ased on the assumption that the effects of the drugs were simply addit ive. According to this definition, synergistic effects were observed a gainst all 3 tumors. Thus, the in vivo and in vitro effects differed. The toxicity of the combination therapy, which was analyzed by estimat ing the body weight change of mice, was no higher than that of CDDP or ETP alone. These results suggest that the excellent clinical effects of CDDP and ETP combination therapy may be attributable not to drug in teraction at the cellular level but to the feasibility of combined use of them at full doses without overlapping side effects.