Combined effect of 5-fluorouracil and carboplatin against human gastric cancer cell lines in vitro and in vivo.

The antitumor activity of a sequential combination of 5-fluorouracil (5-FU) and carboplatin (JM-8) was evaluated using gastric cancer cell lines in vitro and in vivo. In the in vitro study, the sequence of 5-FU followed by JM-8 showed higher antitumor activity than that of the reverse sequence. The sequence of 5-FU at 5 micrograms/ml for 24 h followed by 5 micrograms/ml JM-8 for 24 h showed antitumor activity almost equivalent to that of 10 micrograms/ml 5-FU for 24 h and higher activity than that of 10 micrograms/ml JM-8 for 24 h on two cell lines. To evaluate the antitumor activity and toxicity of 5-FU and JM-8 in vivo, BALB/cA nu/nu mice bearing human gastric cancer xenografts St-15, St-40 and SC-1-NU were administered 5-FU and JM-8 intraperitoneally. The sequence of 5-FU prior to JM-8 showed higher antitumor activity than that of the reverse sequence on all the xenografts, and simultaneous administration of 5-FU and JM-8 showed the most potent antitumor activity on St-40 and SC-1-NU. On the other hand, the sequence of 5-FU before JM-8 showed the lowest toxicity in all the treated groups, in terms of death rate, body weight loss and spleen weight loss. This combination is thought to be a promising chemotherapy regimen, showing high antitumor activity without an increment of toxicity.