Antitumor activity of combination treatment combining gemcitabine with cisplatin or vindesine against human lung cancer xenografted in nude mice

: Gemcitabine is a new ara-C derivative and shows much more potent cytotoxic action than ara-C, which may be explained by the fact that its intracellular concentration can be maintained over a longer period. We investigated anti-tumor activity combining gemcitabine with cisplatin (CDDP) or vindesine (VDS) with a lung cancer line H-74 that was relatively insensitive to gemcitabine. Mice were observed for 8 weeks, including the 4 week treatment period and the subsequent 4 week drug-free period. The tumor growth inhibition rate, histological changes, and side effects were evaluated at 4 and 8 weeks after the initiation of therapy. The anti-tumor effects of treatment combining gemcitabine with CDDP or VDS were more potent and lasted longer than each drug separately. Statistical analysis shows that the treatment combining gemcitabine with CDDP was additive or synergistic at 4 and 8 weeks after initiation, whereas the treatment combining gemcitabine with VDS was only additive at 4 weeks after initiation and additive or synergistic at 8 weeks after initiation. The side effects of both combination groups were less than those observed in only CDDP or VDS-treated animals. These results suggest the usefulness of a combination therapy combining gemcitabine with CDDP or VDS in future clinical applications.